AnaemiaPhase 3NCT02876835
Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Non-Dialysis (ASCEND-ND)
A Phase 3 study testing Daprodustat, Darbepoetin alfa and Iron Therapy in people with Anaemia, run by GlaxoSmithKline at 574 sites in 39 countries.
Trial summary
The purpose of this multi-center event-driven study in non-dialysis (ND) participants with anemia associated with chronic kidney disease (CKD) is to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Anaemia
- What is being tested?
- Daprodustat, Darbepoetin alfa and Iron Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,872 participants
- Where
- 574 sitesin 39 countries
- Study dates
- 27 Sep 2016to 19 Apr 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 to 99 years of age (inclusive)
- CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by electronic eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Erythropoietin-stimulating agents (ESAs)/Hgb: Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1). Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization.
- For Group 1 (not using ESAs), Hgb concentration at Week -8 and Week 1 should be 8 to 10 gram per deciliter (g/dL). For Group 2 (ESA users), Hgb concentration at Week -8 should be 8 to 12 g/dL and at Week 1 should be 8 to 11 g/dL.
- >=80% and <=120% compliance with placebo during run-in period.
- Informed consent (screening only): capable of giving signed informed consent which includes compliance with the requirements and restrictions.
Who cannot join
- Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1).
- Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
- Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
- Transferrin saturation (TSAT) (screening only): <=20%.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia.
- Other causes of anemia: untreated pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.
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- Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=4 weeks prior to screening through to randomization (Day 1).
- MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).
- Stroke or transient ischemic attack: <=4 weeks prior to screening through to randomization (Day 1).
- Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
- Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator.
- Bazett's corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no Q-T Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.
- Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.
- Bilirubin: >1.5xULN at screening.
- Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1) or currently receiving treatment for cancer, or complex kidney cyst (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=4 weeks prior to screening.
- Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or darbepoetin alfa.
- Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
- Other study participation: Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half lives (whichever is longer).
- Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of >30 days.
- Females only: Subject is pregnant [as confirmed by a positive urine human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options.
- Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g., intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Trial locations and contacts
574 sites in 39 countries.
574 sites in 39 countries
United States161 sites
GSK Investigational Site
Alexandria, Virginia, 22304
GSK Investigational Site
Andalusia, Alabama, 36420
GSK Investigational Site
Anderson, South Carolina, 29621
GSK Investigational Site
Arlington, Texas, 76002
GSK Investigational Site
Atlanta, Georgia, 30342
GSK Investigational Site
Augusta, Georgia, 30904
GSK Investigational Site
Augusta, Georgia, 30909
GSK Investigational Site
Augusta, Georgia, 30912
GSK Investigational Site
Austin, Texas, 78751
GSK Investigational Site
Austin, Texas, 78758
GSK Investigational Site
Aventura, Florida, 33180
GSK Investigational Site
Azusa, California, 91702
GSK Investigational Site
Bakersfield, California, 93308
GSK Investigational Site
Bakersfield, California, 93309
GSK Investigational Site
Baltimore, Maryland, 21287
GSK Investigational Site
Baton Rouge, Louisiana, 70808
GSK Investigational Site
Baton Rouge, Louisiana, 70836
GSK Investigational Site
Bethlehem, Pennsylvania, 18017
GSK Investigational Site
Birmingham, Alabama, 35249
GSK Investigational Site
Bluefield, West Virginia, 24701
GSK Investigational Site
Boca Raton, Florida, 33431
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Brooklyn, New York, 11203
GSK Investigational Site
Buffalo, New York, 14215
GSK Investigational Site
Canton, Ohio, 15212
GSK Investigational Site
Charleston, South Carolina, 29425
GSK Investigational Site
Charlotte, North Carolina, 28204
GSK Investigational Site
Chicago, Illinois, 60611
GSK Investigational Site
Chicago, Illinois, 60643
GSK Investigational Site
Chula Vista, California, 91910
GSK Investigational Site
Cincinnati, Ohio, 45206
GSK Investigational Site
Cincinnati, Ohio, 45220
GSK Investigational Site
Columbia, South Carolina, 29209
GSK Investigational Site
Columbus, Georgia, 31904
GSK Investigational Site
Coral Gables, Florida, 33134
GSK Investigational Site
Cordova, Tennessee, 38018
GSK Investigational Site
Corpus Christi, Texas, 78404
GSK Investigational Site
Corsicana, Texas, 75110
GSK Investigational Site
Crystal Lake, Illinois, 60014
GSK Investigational Site
Cudahy, California, 90201
GSK Investigational Site
Cutler Bay, Florida, 33189
GSK Investigational Site
Dallas, Texas, 75237
GSK Investigational Site
Dallas, Texas, 75246
GSK Investigational Site
Des Moines, Iowa, 50309
GSK Investigational Site
Detroit, Michigan, 48202
GSK Investigational Site
Doral, Florida, 33122
GSK Investigational Site
Doylestown, Pennsylvania, 18901
GSK Investigational Site
El Centro, California, 92243
GSK Investigational Site
Escondido, California, 92025
GSK Investigational Site
Fairfax, Virginia, 22033
GSK Investigational Site
Flushing, New York, 11355
GSK Investigational Site
Fort Lauderdale, Florida, 33308
GSK Investigational Site
Fort Wayne, Indiana, 46845
GSK Investigational Site
Glendale, Arizona, 85305
GSK Investigational Site
Glendale, California, 91204
GSK Investigational Site
Granada Hills, California, 91344
GSK Investigational Site
Grand Forks, North Dakota, 58201
GSK Investigational Site
Hampton, Virginia, 23666
GSK Investigational Site
Homestead, Florida, 33033
GSK Investigational Site
Houston, Texas, 77004
GSK Investigational Site
Houston, Texas, 77043
GSK Investigational Site
Houston, Texas, 77084
GSK Investigational Site
Houston, Texas, 77099
GSK Investigational Site
Hudson, Florida, 34667
GSK Investigational Site
Huntsville, Alabama, 35805
GSK Investigational Site
Hutchinson, Kansas, 67502
GSK Investigational Site
Iowa City, Iowa, 52242
GSK Investigational Site
Jackson, Mississippi, 39216
GSK Investigational Site
Jacksonville, Florida, 32224
GSK Investigational Site
Jacksonville, Florida, 32256
GSK Investigational Site
Jeffersonville, Indiana, 47130
GSK Investigational Site
Kalamazoo, Michigan, 49007
GSK Investigational Site
Knoxville, Tennessee, 37923
GSK Investigational Site
La Mesa, California, 91942
GSK Investigational Site
La Palma, California, 90623
GSK Investigational Site
Lancaster, Pennsylvania, 17601
GSK Investigational Site
Las Vegas, Nevada, 89106
GSK Investigational Site
Lauderdale Lakes, Florida, 33313
GSK Investigational Site
Laurelton, New York, 11413
GSK Investigational Site
Lawton, Oklahoma, 73505
GSK Investigational Site
Long Beach, California, 90806
GSK Investigational Site
Los Angeles, California, 90022
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
Louisville, Kentucky, 40202
GSK Investigational Site
Lufkin, Texas, 75904
GSK Investigational Site
McAllen, Texas, 78503
GSK Investigational Site
Memphis, Tennessee, 38163
GSK Investigational Site
Mentor, Ohio, 44060
GSK Investigational Site
Mesa, Arizona, 85202
GSK Investigational Site
Metairie, Louisiana, 70006
GSK Investigational Site
Miami, Florida, 33126
GSK Investigational Site
Miami, Florida, 33143
GSK Investigational Site
Miami, Florida, 33145
GSK Investigational Site
Miami, Florida, 33147
GSK Investigational Site
Miami, Florida, 33150
GSK Investigational Site
Miami, Florida, 33155
GSK Investigational Site
Miami, Florida, 33156
GSK Investigational Site
Miami, Florida, 33165
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Miami, Florida, 33173
GSK Investigational Site
Miami Gardens, Florida, 33169
GSK Investigational Site
Miami Lakes, Florida, 33014
GSK Investigational Site
Michigan City, Indiana, 46360
GSK Investigational Site
Middlebury, Connecticut, 06762
GSK Investigational Site
Minneapolis, Minnesota, 55414
GSK Investigational Site
Montebello, California, 90640
GSK Investigational Site
Mount Prospect, Illinois, 60056
GSK Investigational Site
Nampa, Idaho, 83687
GSK Investigational Site
Nashville, Tennessee, 37205
GSK Investigational Site
National City, California, 91950
GSK Investigational Site
New York, New York, 10021
GSK Investigational Site
New York, New York, 10029
GSK Investigational Site
North Platte, Nebraska, 69101
GSK Investigational Site
Ocala, Florida, 34471
GSK Investigational Site
Orlando, Florida, 32810
GSK Investigational Site
Pembroke Pines, Florida, 33028
GSK Investigational Site
Phoenix, Arizona, 85016
GSK Investigational Site
Phoenix, Arizona, 85027
GSK Investigational Site
Pontiac, Michigan, 48341
GSK Investigational Site
Port Charlotte, Florida, 33952
GSK Investigational Site
Portland, Oregon, 97210
GSK Investigational Site
Potomac, Maryland, 20854
GSK Investigational Site
Quincy, Illinois, 62301
GSK Investigational Site
Raleigh, North Carolina, 27609
GSK Investigational Site
Ridgewood, New York, 11385
GSK Investigational Site
Riverside, California, 92505
GSK Investigational Site
Rocky Mount, North Carolina, 27804
GSK Investigational Site
Roseburg, Oregon, 97471
GSK Investigational Site
Salem, Virginia, 24153
GSK Investigational Site
San Antonio, Texas, 78202
GSK Investigational Site
San Antonio, Texas, 78212
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
San Antonio, Texas, 78258
GSK Investigational Site
San Diego, California, 92103
GSK Investigational Site
San Diego, California, 92111
GSK Investigational Site
San Luis Obispo, California, 93405
GSK Investigational Site
Scottsdale, Arizona, 48201
GSK Investigational Site
Simi Valley, California, 93065
GSK Investigational Site
South Miami, Florida, 33143
GSK Investigational Site
Springfield, Illinois, 62702
GSK Investigational Site
St Louis, Missouri, 63106
GSK Investigational Site
St Louis, Missouri, 63110
GSK Investigational Site
Sumter, South Carolina, 29150
GSK Investigational Site
Takoma Park, Maryland, 20912-6385
GSK Investigational Site
Tampa, Florida, 33612
GSK Investigational Site
Tarzana, California, 91356
GSK Investigational Site
Temple, Texas, 76508
GSK Investigational Site
Temple Terrace, Florida, 33637
GSK Investigational Site
The Bronx, New York, 10461
GSK Investigational Site
The Bronx, New York, 10467
GSK Investigational Site
Tucson, Arizona, 85745
GSK Investigational Site
Tupelo, Mississippi, 38801
GSK Investigational Site
Upland, Pennsylvania, 19013
GSK Investigational Site
Washington D.C., District of Columbia, 20037
GSK Investigational Site
Waxahachie, Texas, 75165
GSK Investigational Site
Whittier, California, 90602
GSK Investigational Site
Wichita, Kansas, 67214
GSK Investigational Site
Wilmington, North Carolina, 28401
GSK Investigational Site
Winston-Salem, North Carolina, 27103
GSK Investigational Site
Wyomissing, Pennsylvania, 19610
GSK Investigational Site
Yonkers, New York, 10704
India29 sites
GSK Investigational Site
Ahmedabad, 380054
GSK Investigational Site
Ahmedabad, 380059
GSK Investigational Site
Bangalore, 560054
GSK Investigational Site
Bangalore, 560055
GSK Investigational Site
Calicut, 673008
GSK Investigational Site
Chandigarh, 160012
GSK Investigational Site
Chennai, 600037
GSK Investigational Site
Chennai, Tamil Nadu, 600 006
GSK Investigational Site
Delhi, 110076
GSK Investigational Site
Ghaziabad, 201012
GSK Investigational Site
Gūrgaon, 122001
GSK Investigational Site
Hyderabad, 500012
GSK Investigational Site
Hyderabad, 500034
GSK Investigational Site
Jaipur, 302004
GSK Investigational Site
Jaipur, 302018
GSK Investigational Site
Lucknow, 226014
GSK Investigational Site
Manipal, 576104
GSK Investigational Site
Mumbai, 400008
GSK Investigational Site
Mumbai, 400016
GSK Investigational Site
Nadiād, 387001
GSK Investigational Site
Nagpur, 440010
GSK Investigational Site
New Delhi, 110002
GSK Investigational Site
New Delhi, 110017
GSK Investigational Site
New Delhi, 110025
GSK Investigational Site
New Delhi, 110060
GSK Investigational Site
Pune, 411004
GSK Investigational Site
Pune, 411033
GSK Investigational Site
Secunderabad, 560020
GSK Investigational Site
Trivandrum, 695011
South Korea26 sites
GSK Investigational Site
Anyang-Si, Gyeonggi-do, 14068
GSK Investigational Site
Bucheon-si, 420-767
GSK Investigational Site
Busan, 48108
GSK Investigational Site
Daegu, 41931
GSK Investigational Site
Daegu, 41944
GSK Investigational Site
Daejeon, 301-721
GSK Investigational Site
Goyang-si, 10444
GSK Investigational Site
Ilsanseo-gu, Goyang-si,, 10380
GSK Investigational Site
Incheon, 021431
GSK Investigational Site
Incheon, 405-760
GSK Investigational Site
Jeonju, 54987
GSK Investigational Site
Seongnam, 13620
GSK Investigational Site
Seoul, 06973
GSK Investigational Site
Seoul, 07061
GSK Investigational Site
Seoul, 08308
GSK Investigational Site
Seoul, 134-727
GSK Investigational Site
Seoul, 135-710
GSK Investigational Site
Seoul, 137-701
GSK Investigational Site
Seoul, 158-710
GSK Investigational Site
Seoul, 3080
GSK Investigational Site
Seoul, ?02447
GSK Investigational Site
Seoul, ?05355
GSK Investigational Site
Suwon, 16499
GSK Investigational Site
Suwon, 442-723
GSK Investigational Site
Uijeongbu-si, 11765
GSK Investigational Site
Wŏnju, 26426
Mexico25 sites
GSK Investigational Site
Aguascalientes, 20230
GSK Investigational Site
Chihuahua City, 31203
GSK Investigational Site
Chihuahua City, 31217
GSK Investigational Site
Ciudad de Mexico, State of Mexico, 14080
GSK Investigational Site
Cuernavaca, Morelos, 62448
GSK Investigational Site
Culiacán, Sinaloa, 80200
GSK Investigational Site
Culiacán, Sinaloa, 80230
GSK Investigational Site
Culiacán, 80030
GSK Investigational Site
Durango, Durango, 34000
GSK Investigational Site
Guadalajara, Jalisco, 44600
GSK Investigational Site
Guadalajara, Jalisco, 44620
GSK Investigational Site
León, Guanajuato, 37000
GSK Investigational Site
León, Guanajuato, 37530
GSK Investigational Site
Mazatlán, Sinaloa, 82020
GSK Investigational Site
Mérida, Yucatán, 97133
GSK Investigational Site
Mérida, Yucatán, CP 97070
GSK Investigational Site
Mexico City, 06100
GSK Investigational Site
Mexico City, ?03800
GSK Investigational Site
Monterrey, Nuevo León, 64000
GSK Investigational Site
Querétaro City, Querétaro, 76000
GSK Investigational Site
Saltillo, Coahuila, CP 25230
GSK Investigational Site
Tlalnepantla, 54055
GSK Investigational Site
Torreón, Coahuila, 27000
GSK Investigational Site
Veracruz, 91020
GSK Investigational Site
Zapopan, Jalisco, 45030
United Kingdom22 sites
GSK Investigational Site
Birmingham, B9 5SS
GSK Investigational Site
Bristol, BS10 5NB
GSK Investigational Site
Cambridge, CB2 0QQ
GSK Investigational Site
Cardiff, CF14 4XW
GSK Investigational Site
Derby, DE22 3NE
GSK Investigational Site
Doncaster, DN2 5LT
GSK Investigational Site
Fife, KY2 5AH
GSK Investigational Site
Glasgow, G51 4TF
GSK Investigational Site
Hampstead, London, NW3 2QG
GSK Investigational Site
Hull, HU3 2JZ
GSK Investigational Site
Leeds, LS9 7TF
GSK Investigational Site
Liverpool, Merseyside, L7 8XP
GSK Investigational Site
London, E1 1BB
GSK Investigational Site
London, SE5 9RS
GSK Investigational Site
Manchester, M13 9WL
GSK Investigational Site
Middlesbrough, TS4 3BW
GSK Investigational Site
Oxford, OX3 7LE
GSK Investigational Site
Preston, Lancashire, PR2 9HT
GSK Investigational Site
Salford, M6 8HD
GSK Investigational Site
Stevenage, Hertfordshire, SG1 4AB
GSK Investigational Site
Wolverhampton, West Midlands, WV10 0QP
GSK Investigational Site
York, YO31 8HE
Brazil20 sites
GSK Investigational Site
Belo Horizonte, 30150-320
GSK Investigational Site
Brasília, 70840-901
GSK Investigational Site
Curitiba, Paraná, 80440-020
GSK Investigational Site
Curitiba, Paraná, 80730-150
GSK Investigational Site
Curitiba, Paraná, CEP 80230-130
GSK Investigational Site
Feira de Santana, 44001-465
GSK Investigational Site
Joinville, 89201-010
GSK Investigational Site
Juiz de Fora, 36036-330
GSK Investigational Site
Passo Fundo, Rio Grande do Sul, 99010-080
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90035-074
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90035-903
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90610-000
GSK Investigational Site
Salvador, Estado de Bahia, 40415-065
GSK Investigational Site
São José do Rio Preto, São Paulo, 15090-000
GSK Investigational Site
São Paulo, 01323903
GSK Investigational Site
São Paulo, 04039-000
GSK Investigational Site
São Paulo, ?01323-001
GSK Investigational Site
São Paulo, ?04005-000
GSK Investigational Site
São Paulo, ?08270-070
GSK Investigational Site
Votuporanga, São Paulo, 15500-003
Greece19 sites
GSK Investigational Site
Alexandroupoli, 68100
GSK Investigational Site
Arta, 471 00
GSK Investigational Site
Athens, 115 26
GSK Investigational Site
Athens, 11526
GSK Investigational Site
Athens, 11527
GSK Investigational Site
Athens, 12462
GSK Investigational Site
Efkarpia, 564 29
GSK Investigational Site
Heraklion-Crete, 71110
GSK Investigational Site
Ioannina, 45001
GSK Investigational Site
Ioannina, 45500
GSK Investigational Site
Komotini, 69100
GSK Investigational Site
Larissa, 41100
GSK Investigational Site
Melíssia, 15127
GSK Investigational Site
Pátrai, 26500
GSK Investigational Site
Thessaloniki, 546 42
GSK Investigational Site
Thessaloniki, 54636
GSK Investigational Site
Thessaloniki, 551 34
GSK Investigational Site
Thessaloniki, 57001
GSK Investigational Site
Thessaloniki, 57010
Ukraine18 sites
GSK Investigational Site
Cherkasy, 18009
GSK Investigational Site
Chernihiv, 14029
GSK Investigational Site
Chernivtsi, 58005
GSK Investigational Site
Ivano-Frankivsk, 76008
GSK Investigational Site
Kharkiv, 61039
GSK Investigational Site
Kherson, 73039
GSK Investigational Site
Kiev, ?04107
GSK Investigational Site
Kyiv, 01014
GSK Investigational Site
Kyiv, 04112
GSK Investigational Site
Kyiv, ?01023
GSK Investigational Site
Kyiv, ?04050
GSK Investigational Site
Lutsk, 43000
GSK Investigational Site
Mykolaiv, 54058
GSK Investigational Site
Poltava, 36011
GSK Investigational Site
Ternopil, 46002
GSK Investigational Site
Zaporizhzhya, 69001
GSK Investigational Site
Zaporizhzhya, 69600
GSK Investigational Site
Zhytomyr, 10002
Argentina16 sites
GSK Investigational Site
Buenos Aires, 1425
GSK Investigational Site
Buenos Aires, C1181ACH
GSK Investigational Site
Buenos Aires, CP1431FWO
GSK Investigational Site
Ciudad Evita, Buenos Aires, B1778IFA
GSK Investigational Site
Córdoba, Córdoba Province, 5000
GSK Investigational Site
Córdoba, Córdoba Province, X5016KEH
GSK Investigational Site
Coronel Suárez, Buenos Aires, 7540
GSK Investigational Site
Corrientes, W3400AMZ
GSK Investigational Site
Formosa, P3600LLD
GSK Investigational Site
Junín, Buenos Aires, B6000GMA
GSK Investigational Site
La Plata, B1902COS
GSK Investigational Site
Mar del Plata, Buenos Aires, 7600
GSK Investigational Site
Mendoza, M5500AFA
GSK Investigational Site
Morón, B1708DPO
GSK Investigational Site
Pergamino, Buenos Aires, B2700CPM
GSK Investigational Site
San Miguel de Tucumán, T4000AHL
Spain15 sites
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08003
GSK Investigational Site
Barcelona, 08011
GSK Investigational Site
Barcelona, 08025
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Burela de Cabo, 27880
GSK Investigational Site
Cáceres, 10003
GSK Investigational Site
Ciudad Real, 13002
GSK Investigational Site
Girona, 17007
GSK Investigational Site
Guadalajara, 19002
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Majadahonda, Madrid, 28222
GSK Investigational Site
Mollet del Vallès, ?08100
GSK Investigational Site
Santiago de Compostela, 15706
GSK Investigational Site
Seville, 41071
Australia14 sites
GSK Investigational Site
Concord, New South Wales, 2139
GSK Investigational Site
Garran, Australian Capital Territory, 2606
GSK Investigational Site
Gosford, New South Wales, 2250
GSK Investigational Site
Kingswood, New South Wales, 2747
GSK Investigational Site
Kogarah, New South Wales, 2217
GSK Investigational Site
Liverpool, 2107
GSK Investigational Site
Melbourne, Victoria, 3004
GSK Investigational Site
Nambour, Queensland, 4560
GSK Investigational Site
Nedlands, Western Australia, 6009
GSK Investigational Site
Randwick, New South Wales, 2031
GSK Investigational Site
Reservoir, Victoria, 3073
GSK Investigational Site
St Albans, Victoria, 3021
GSK Investigational Site
St Leonards, New South Wales, 2065
GSK Investigational Site
Wollongong, New South Wales, 2500
Bulgaria14 sites
GSK Investigational Site
Blagoevgrad, 2700
GSK Investigational Site
Burgas, 8000
GSK Investigational Site
Dobrich, 9300
GSK Investigational Site
Gabrovo, 5300
GSK Investigational Site
Lom, 3600
GSK Investigational Site
Pazardzhik, 4400
GSK Investigational Site
Plovdiv, 4000
GSK Investigational Site
Sliven, 8800
GSK Investigational Site
Smolyan, 4700
GSK Investigational Site
Sofia, 1233
GSK Investigational Site
Sofia, 1709
GSK Investigational Site
Stara Zagora, 6000
GSK Investigational Site
Varna, 9000
GSK Investigational Site
Veliko Tarnovo, 5000
Russia14 sites
GSK Investigational Site
Irkutsk, 664049
GSK Investigational Site
Kemerovo, 650060
GSK Investigational Site
Krasnodar, 350029
GSK Investigational Site
Moscow, 119121
GSK Investigational Site
Mytischi, 141009
GSK Investigational Site
Omsk, 644112
GSK Investigational Site
Podolsk, 142110
GSK Investigational Site
Ryazan, 390026
GSK Investigational Site
Saint Petersburg, 194104
GSK Investigational Site
Saint Petersburg, 196247
GSK Investigational Site
Smolensk, 214006
GSK Investigational Site
Ulyanovsk, 432063
GSK Investigational Site
Volzhsky, 404120
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Yaroslavl, 150062
Italy13 sites
GSK Investigational Site
Cagliari, Sardinia, ?09100
GSK Investigational Site
Catanzaro, Calabria, 88100
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Foggia, Apulia, 71100
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Genoa, Liguria, 16132
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Imola, 40026
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Lecco, Lombardy, 23900
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Mestre, 30122
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Milan, Lombardy, 20132
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Naples, Campania, 80131
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Pavia, Lombardy, 27100
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Piacenza, Emilia-Romagna, 29100
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Reggio Emilia, Emilia-Romagna, 42123
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Turin, Piedmont, 10154
Belgium10 sites
GSK Investigational Site
Aalst, 9300
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Baudour, 7331
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Bruges, 8310
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Brussels, 1200
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Ieper, 8900
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Leuven, 3000
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Liège, 4000
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Roeselare, 8800
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Ronse, 9600
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Sint-Niklaas, 9100
Canada10 sites
GSK Investigational Site
Brampton, Ontario, L6T 0G1
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Edmonton, Alberta, T6G 2B7
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Greenfield Park, Quebec, J4V 2H1
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Halifax, Nova Scotia, B3H 1V8
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London, Ontario, N6A 5A5
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Mississauga, Ontario, L4V 1P1
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Mississauga, Ontario, L5M 2V8
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Montreal, Quebec, H3G 1A4
GSK Investigational Site
Québec, Quebec, G1R 2J6
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Toronto, Ontario, M4C 5T2
Czechia10 sites
GSK Investigational Site
Beroun, 26601
GSK Investigational Site
Český Krumlov, 38127
GSK Investigational Site
Ivančice, 664 95
GSK Investigational Site
Jilemnice, 514 01
GSK Investigational Site
Mariánské Lázně, 353 01
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Nový Jičín, 74101
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Pardubice, 53203
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Prague, 128 08
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Prague, 140 21
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Sokolov, 356 01
Poland10 sites
GSK Investigational Site
Bialystok, 15-540
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Brzeg, 49301
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Gdansk, 80-952
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Katowice, 40-027
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Kielce, 25-736
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Kołobrzeg, 78-100
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Lodz, 92-213
GSK Investigational Site
Radom, 26-610
GSK Investigational Site
Szczecin, 70-111
GSK Investigational Site
Żyrardów, 96-300
Taiwan10 sites
GSK Investigational Site
Kaohsiung City, 807
GSK Investigational Site
Kaohsiung City, 833
GSK Investigational Site
Keelung, 204
GSK Investigational Site
New Taipei City, 220
GSK Investigational Site
Tainan, 704
GSK Investigational Site
Taipei, 10002
GSK Investigational Site
Taipei, 104
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Taipei, 112
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Taipei, 116
GSK Investigational Site
Taoyuan Hsien, 333
France9 sites
GSK Investigational Site
Annonay, 07103
GSK Investigational Site
Boulogne-Billancourt, 92100
GSK Investigational Site
Caen, 14033
GSK Investigational Site
Clermont-Ferrand, 63000
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Lyon, 69003
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Montpellier, 34295
GSK Investigational Site
Mulhouse, 68100
GSK Investigational Site
Poitiers, 86021
GSK Investigational Site
Saint-Ouen, 93400
Germany9 sites
GSK Investigational Site
Cloppenburg, Lower Saxony, 49661
GSK Investigational Site
Cologne, 50937
GSK Investigational Site
Düsseldorf, North Rhine-Westphalia, 40210
GSK Investigational Site
Kaiserslautern, Rhineland-Palatinate, 67655
GSK Investigational Site
Leipzig, Saxony, 04129
GSK Investigational Site
Mannheim, Baden-Wurttemberg, 68167
GSK Investigational Site
Munich, Bavaria, 81675
GSK Investigational Site
Münster, North Rhine-Westphalia, 48149
GSK Investigational Site
Wiesbaden, 65191
Philippines9 sites
GSK Investigational Site
Baguio City, Benguet, 2600
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Cebu City, 6000
GSK Investigational Site
Dasmariñas, 4114
GSK Investigational Site
Iloilo City, 5000
GSK Investigational Site
Manila, 1000
GSK Investigational Site
Pasig, 1605
GSK Investigational Site
Quezon City, 1100
GSK Investigational Site
San Juan City, 1500
GSK Investigational Site
Sto Tomas, 4234
Turkey (Türkiye)9 sites
GSK Investigational Site
Adana, ?01330
GSK Investigational Site
Ankara, ?06100
GSK Investigational Site
Antalya, ?07059
GSK Investigational Site
Edirne, 22030
GSK Investigational Site
Eskişehir, 26480
GSK Investigational Site
Istanbul, 34130
GSK Investigational Site
Istanbul, 34381
GSK Investigational Site
Istanbul, 34899
GSK Investigational Site
Kayseri, 38039
Hungary8 sites
GSK Investigational Site
Baja, 6500
GSK Investigational Site
Balatonfüred, 8230
GSK Investigational Site
Esztergom, 2500
GSK Investigational Site
Kecskemét, 6000
GSK Investigational Site
Miskolc, 3526
GSK Investigational Site
Pécs, 7623
GSK Investigational Site
Salgótarján, 3100
GSK Investigational Site
Szigetvár, 7900
Israel8 sites
GSK Investigational Site
Ashkelon, 78278
GSK Investigational Site
Hadera, PO Box 169
GSK Investigational Site
Haifa, 31096
GSK Investigational Site
Kfar Saba, 44281
GSK Investigational Site
Nahariya, 22100
GSK Investigational Site
Nazareth, 16100
GSK Investigational Site
Poria – Neve Oved, 15208
GSK Investigational Site
Tsrifin, 70300
Malaysia7 sites
GSK Investigational Site
Alor Star, 55600
GSK Investigational Site
George Town, 10990
GSK Investigational Site
Ipoh, 30450
GSK Investigational Site
Kuala Lumpur, 50603
GSK Investigational Site
Kuala Pahang, 28000
GSK Investigational Site
Kuantan, 25100
GSK Investigational Site
Lumut, 32040
Portugal7 sites
GSK Investigational Site
Amadora, 2720-276
GSK Investigational Site
Aveiro, 3814-501
GSK Investigational Site
Covilha, 6200-000
GSK Investigational Site
Lisbon, 1069-166
GSK Investigational Site
Lisbon, 1250-189
GSK Investigational Site
Lisbon, 1400-195
GSK Investigational Site
Torres Novas, 2350-754
Thailand7 sites
GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Bangkok, 10400
GSK Investigational Site
Bangkok, 11000
GSK Investigational Site
Bangkoknoi, 10700
GSK Investigational Site
Chiang Mai, 50200
GSK Investigational Site
Khon Kaen, 40002
GSK Investigational Site
Pathum Thani, 12120
Romania6 sites
GSK Investigational Site
Bucharest, 022328
GSK Investigational Site
Bucharest, ?022328
GSK Investigational Site
Bucharest, ?042122
GSK Investigational Site
Constanța, 900591
GSK Investigational Site
Oradea, 410469
GSK Investigational Site
Timișoara, 300723
Colombia5 sites
GSK Investigational Site
Barranquilla, 760002
GSK Investigational Site
Bogotá, 111711
GSK Investigational Site
Cali, 760007
GSK Investigational Site
Floridablanca, 681001
GSK Investigational Site
Medellín, 050012
New Zealand5 sites
GSK Investigational Site
Dunedin, 9016
GSK Investigational Site
Hamilton, 2001
GSK Investigational Site
Hastings, 4156
GSK Investigational Site
Otahuhu, 1640
GSK Investigational Site
Takapuna, Auckland, ?0740
Denmark4 sites
GSK Investigational Site
Aalborg, DK-9000
GSK Investigational Site
Holstebro, 7500
GSK Investigational Site
Kolding, 6000
GSK Investigational Site
Odense C, 5000
Hong Kong4 sites
GSK Investigational Site
Hong Kong
GSK Investigational Site
Lai Chi Kok
GSK Investigational Site
New Territories
GSK Investigational Site
Tsuen Wan
Singapore4 sites
GSK Investigational Site
Singapore, 119074
GSK Investigational Site
Singapore, 169608
GSK Investigational Site
Singapore, 308433
GSK Investigational Site
Singapore, 768828
South Africa4 sites
GSK Investigational Site
Cape Town, 7500
GSK Investigational Site
Cape Town, 7925
GSK Investigational Site
Port Elizabeth, Eastern Cape, 6001
GSK Investigational Site
Somerset West, 7130
Vietnam4 sites
GSK Investigational Site
Hà Nội, 10000
GSK Investigational Site
Haiphong, 180000
GSK Investigational Site
Hanoi, 11000
GSK Investigational Site
Ho Chi Minh City, 700000
Estonia3 sites
GSK Investigational Site
Jämejala Village, 71024
GSK Investigational Site
Tallinn, EE-13419
GSK Investigational Site
Tartu, 50501
Netherlands3 sites
GSK Investigational Site
Amsterdam, 1081 HV
GSK Investigational Site
Deventer, 7416 SE
GSK Investigational Site
Rotterdam, 3079 DZ
Sweden3 sites
GSK Investigational Site
Örebro, SE-701 85
GSK Investigational Site
Stockholm, SE-141 86
GSK Investigational Site
Uppsala, SE-75185
About this study
Official title: A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Darbepoetin Alfa
The purpose of this multi-center event-driven study in non-dialysis (ND) participants with anemia associated with chronic kidney disease (CKD) is to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa.
- Conditions
- Anaemia
- Being tested
- Daprodustat, Darbepoetin alfa, Placebo, Iron Therapy
- Keywords
- GSK1278863, hemoglobin, anemia, non-dialysis, erythropoiesis stimulating agents, daprodustat, chronic kidney disease
- Medical subject headings
- Anemia, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaprodustatDrug
The initial dose or oral daprodustat for ESA naïve subjects is based on Hgb and for ESA users is based on prior ESA dose. The dose is adjusted thereafter in order to achieve the target range.
Darbepoetin alfaDrug
The initial dose of darbepoetin alfa to be administered for SC injection for ESA naïve subjects is based in Hgb and weight, and for ESA users is based on converting the prior ESA dose to the nearest available study darbepoetin alfa dose. The dose is adjusted thereafter in order to achieve the target range. IV darbepoetin alfa can be considered for participants transitioning to hemodialysis.
PlaceboDrug
Oral placebo tablets will be taken from Week -4 up to randomization (Day 1).
Iron TherapyDrug
Participants will receive supplemental iron therapy if ferritin is <=100 ng/mL or TSAT is <=20%. The investigator will choose the route of administration and dose of iron.
| Study group | Role | What they receive |
|---|---|---|
| Daprodustat | Experimental | Participants will receive oral daprodustat once daily. Receives: Drug: Daprodustat; Drug: Placebo; Drug: Iron Therapy |
| Darbepoetin alfa | Active comparator | Participants will be administered darbepoetin alfa subcutaneously (SC). Receives: Drug: Darbepoetin alfa; Drug: Placebo; Drug: Iron Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)
Time to MACE defined as time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, current erythropoiesis-stimulating agents (ESA) use at randomization and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied [*] number of participants with at least 1 event) divided by [/] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Mean Change From Baseline in Hgb Levels Over the Evaluation Period (Week 28 to Week 52)
Blood samples were collected from participants for Hgb measurements. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of covariance (ANCOVA) model with terms for treatment, Baseline Hgb, current ESA use and region.
Measured: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary outcomes (39)
Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period (Superiority Analysis)
Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Chronic Kidney Disease (CKD) Progression During CV Events Follow-up Time Period
Progression of CKD defined as: 40% decline in estimated glomerular filtration rate (eGFR) from Baseline or end stage renal disease (ESRD) as defined by either initiating chronic dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated or kidney transplantation. Time to first occurrence of CKD progression was analyzed using Fine and Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) +1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period
Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status follow-up time period.
Measured: Up to 4.3 person-years for vital status follow-up time period
Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period
Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)
Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period
Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period
All-cause hospitalization events were hospital admissions recorded on the hospitalization electronic case report form (eCRF) form with a hospitalization duration >=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period
All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization electronic case record form with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24hours.Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, current ESA use at randomization and region as covariates.Time to the first occurrence was computed as(event date - randomization date)+1. Incidence rate per 100 person years calculated as(100*number of participants with at least 1event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period
Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Confirmed 40% Decline in eGFR During CV Events Follow-up Time Period
Time to first occurrence of confirmed 40% decline in eGFR was analyzed using a Fine \& Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Chronic Dialysis During CV Events Follow-up Time Period
Time to first occurrence of chronic dialysis was analyzed using a Fine \& Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Chronic dialysis is defined by either initiating dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Kidney Transplant During CV Events Follow-up Time Period
Time to first occurrence of kidney transplant were analyzed using a Fine \& Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Measured: Up to 4.3 person-years for CV follow-up time period
Change From Baseline in Post-randomization Hgb Levels at Week 52
Blood samples were collected from participants for Hgb measurements. Change from Baseline was defined as post-randomization value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, current ESA use, region, Baseline Hgb and Baseline Hgb by time and treatment by time interactions.
Measured: Baseline (Pre-dose on Day 1) and Week 52
Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hgb responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL.
Measured: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)].
Measured: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)].
Measured: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)].
Measured: Week 28 to end of study (4.3 person-years for follow-up time period)
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)].
Measured: Week 28 to end of study (4.3 person-years for follow-up time period)
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is the average (BP) in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + current ESA use at randomization + region + Baseline value + Baseline value*time + treatment group*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented.
Measured: Baseline (Week -4) and Week 52
Change From Baseline in SBP, DBP, MAP at End of Treatment
SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using ANCOVA model with terms for treatment group, current ESA use at randomization, region and Baseline value. Data for post-dialysis BP measurements have been presented.
Measured: Baseline (Week -4) and 51.1 months
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
BP exacerbation event (based on post-dialysis) was defined as: SBP >= 25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, current ESA use at randomization and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented.
Measured: Day 1 to end of treatment (51.1 months)
Number of Participants With at Least One BP Exacerbation Event During Study
BP exacerbation was defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one BP exacerbation event is presented.
Measured: Day 1 to end of treatment (51.1 months)
Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented.
Measured: Day 1 to 51.1 months
Change From Baseline in On-treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher score represents better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain (b pain), general health (GH), mental health (MH), role-emotional (RE) (role limitations caused by emotional problems), role-physical (RP) (role limitations caused by physical problems), social functioning (SF), physical functioning and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline (BL) was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date.
Measured: Baseline (Pre-dose on Day 1) and Week 52
Change From Baseline in On-treatment EQ Visual Analogue Scale (EQ-VAS) at Week 52
The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1) and Week 52
Change From Baseline in On-treatment Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Weeks 8, 12, 28, 52
CKD-AQ is 21-item patient reported outcome measure assessing symptoms and symptom impact in participants with anemia associated with CKD. It had 3 domains: 1.Tired/Low Energy (LE)/Weak scale consisting of 10 items; 2.Chest Pain (CP)/Shortness of Breath (SOB) scale consisting of 4 items; and 3.Cognitive (Cog) scale consisting of 3 items. The 4 CKD-AQ single items are: shortness of breath, no activity; severity-short breath (S-SB), resting; difficulty standing (diff. std.)for long time (LT) and difficulty sleeping (diff sleep). Single-item were recorded based on a 0-100 scoring with 0=worst possible and 100=best possible score. Three domains scores were calculated as average of items in each domain and ranged from 0-100 where 0=worst possible and 100=best possible score. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Day 1) and Weeks 8, 12, 28, 52
Change From Baseline in On-treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52
The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated more disease severity. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in Post-randomization Estimated Glomerular Filtration Rate (eGFR) at Week 52
Blood samples were collected to analyze estimated glomerular filtration rate. Change from Baseline was calculated as post-Baseline visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Measured: Baseline (Pre-dose on Day 1) and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2016 (estimated)
- Study start27 Sep 2016
- Primary completion19 Apr 2021
- Study completion19 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AnaemiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,872 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02876835
- Sponsor's protocol ID
- 200808
- Other IDs
- 2016-000542-65, 2016
- Status last verified
- Mar 2024
- First submitted
- 19 Aug 2016
- Last updated
- 2 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Publications
Singh AK, Carroll K, McMurray JJV, Solomon S, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Wiecek A, Blackorby A, Cizman B, Cobitz AR, Davies R, DiMino TL, Kler L, Meadowcroft AM, Taft L, Perkovic V; ASCEND-ND Study Group. Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis. N Engl J Med. 2021 Dec 16;385(25):2313-2324. doi: 10.1056/NEJMoa2113380. Epub 2021 Nov 5.
PubMed 34739196Perkovic V, Blackorby A, Cizman B, Carroll K, Cobitz AR, Davies R, DiMino TL, Jha V, Johansen KL, Lopes RD, Kler L, Macdougall IC, McMurray JJV, Meadowcroft AM, Obrador GT, Solomon S, Taft L, Wanner C, Waikar SS, Wheeler DC, Wiecek A, Singh AK. The ASCEND-ND trial: study design and participant characteristics. Nephrol Dial Transplant. 2022 Oct 19;37(11):2157-2170. doi: 10.1093/ndt/gfab318.
PubMed 34865143Cunningham JW, Claggett BL, Lopes RD, McMurray JJV, Perkovic V, Carroll K, Hiemstra T, Khavandi K, Lukas MA, Ranganathan P, Shannon J, van Adelsberg J, Singh AK, Solomon SD. Daprodustat and Heart Failure in CKD. J Am Soc Nephrol. 2024 May 1;35(5):607-617. doi: 10.1681/ASN.0000000000000321. Epub 2024 Feb 22.
PubMed 38383961Singh AK, McCausland FR, Claggett BL, Wanner C, Wiecek A, Atkins MB, Carroll K, Perkovic V, McMurray JJV, Wittes J, Snapinn S, Blackorby A, Meadowcroft A, Barker T, DiMino T, Mallett S, Cobitz AR, Solomon SD. Analysis of on-treatment cancer safety events with daprodustat versus conventional erythropoiesis-stimulating agents-post hoc analyses of the ASCEND-ND and ASCEND-D trials. Nephrol Dial Transplant. 2023 Jul 31;38(8):1890-1897. doi: 10.1093/ndt/gfac342.
PubMed 36565721Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PubMed 36005278
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Darbepoetin Alfa
- ClinicalTrials.gov ID
- NCT02876835
- Acronym / sponsor ID
- 200808
- Conditions
- Anaemia
- Keywords
- GSK1278863, hemoglobin, anemia, non-dialysis, erythropoiesis stimulating agents, daprodustat, chronic kidney disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,872 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 27 Sep 2016 (actual)
- Primary completion
- 19 Apr 2021 (actual)
- Study completion
- 19 Apr 2021 (actual)
- First posted
- 24 Aug 2016 (estimated)
- Results
- Posted 14 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this multi-center event-driven study in non-dialysis (ND) participants with anemia associated with chronic kidney disease (CKD) is to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daprodustat | Experimental | Drug: Daprodustat, Drug: Placebo, Drug: Iron TherapyParticipants will receive oral daprodustat once daily. |
| Darbepoetin alfa | Active comparator | Drug: Darbepoetin alfa, Drug: Placebo, Drug: Iron TherapyParticipants will be administered darbepoetin alfa subcutaneously (SC). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age: 18 to 99 years of age (inclusive)
- CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by electronic eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Erythropoietin-stimulating agents (ESAs)/Hgb: Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1). Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization.
- For Group 1 (not using ESAs), Hgb concentration at Week -8 and Week 1 should be 8 to 10 gram per deciliter (g/dL). For Group 2 (ESA users), Hgb concentration at Week -8 should be 8 to 12 g/dL and at Week 1 should be 8 to 11 g/dL.
- >=80% and <=120% compliance with placebo during run-in period.
Key exclusion criteria (22 listed)
- Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1).
- Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
- Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
- Transferrin saturation (TSAT) (screening only): <=20%.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaprodustatThe initial dose or oral daprodustat for ESA naïve subjects is based on Hgb and for ESA users is based on prior ESA dose. The dose is adjusted thereafter in order to achieve the target range. | Drug | Daprodustat |
| Darbepoetin alfaThe initial dose of darbepoetin alfa to be administered for SC injection for ESA naïve subjects is based in Hgb and weight, and for ESA users is based on converting the prior ESA dose to the nearest available study darbepoetin alfa dose. The dose is adjusted thereafter in order to achieve the target range. IV darbepoetin alfa can be considered for participants transitioning to hemodialysis. | Drug | Darbepoetin alfa |
| PlaceboOral placebo tablets will be taken from Week -4 up to randomization (Day 1). | Drug | Daprodustat, Darbepoetin alfa |
| Iron TherapyParticipants will receive supplemental iron therapy if ferritin is <=100 ng/mL or TSAT is <=20%. The investigator will choose the route of administration and dose of iron. | Drug | Daprodustat, Darbepoetin alfa |
Primary outcome
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to MACE defined as time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, current erythropoiesis-stimulating agents (ESA) use at randomization and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied [*] number of participants with at least 1 event) divided by [/] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Mean Change From Baseline in Hgb Levels Over the Evaluation Period (Week 28 to Week 52)
Time frame: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Blood samples were collected from participants for Hgb measurements. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of covariance (ANCOVA) model with terms for treatment, Baseline Hgb, current ESA use and region.
39 secondary outcomes
Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period (Superiority Analysis)
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Chronic Kidney Disease (CKD) Progression During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period
Time frame: Up to 4.3 person-years for vital status follow-up time period
Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Confirmed 40% Decline in eGFR During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Chronic Dialysis During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Time to First Occurrence of Kidney Transplant During CV Events Follow-up Time Period
Time frame: Up to 4.3 person-years for CV follow-up time period
Change From Baseline in Post-randomization Hgb Levels at Week 52
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Time frame: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Time frame: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Time frame: Week 28 to Week 52
Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis
Time frame: Week 28 to end of study (4.3 person-years for follow-up time period)
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis
Time frame: Week 28 to end of study (4.3 person-years for follow-up time period)
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
Time frame: Baseline (Week -4) and Week 52
Change From Baseline in SBP, DBP, MAP at End of Treatment
Time frame: Baseline (Week -4) and 51.1 months
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
Time frame: Day 1 to end of treatment (51.1 months)
Number of Participants With at Least One BP Exacerbation Event During Study
Time frame: Day 1 to end of treatment (51.1 months)
Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Time frame: Day 1 to 51.1 months
Change From Baseline in On-treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in On-treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Change From Baseline in On-treatment EQ Visual Analogue Scale (EQ-VAS) at Week 52
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Change From Baseline in On-treatment Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Weeks 8, 12, 28, 52
Time frame: Baseline (Day 1) and Weeks 8, 12, 28, 52
Change From Baseline in On-treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Change From Baseline in Post-randomization Estimated Glomerular Filtration Rate (eGFR) at Week 52
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34739196Singh AK, Carroll K, McMurray JJV, Solomon S, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Wiecek A, Blackorby A, Cizman B, Cobitz AR, Davies R, DiMino TL, Kler L, Meadowcroft AM, Taft L, Perkovic V; ASCEND-ND Study Group. Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis. N Engl J Med. 2021 Dec 16;385(25):2313-2324. doi: 10.1056/NEJMoa2113380. Epub 2021 Nov 5.
- Background: PubMed 34865143Perkovic V, Blackorby A, Cizman B, Carroll K, Cobitz AR, Davies R, DiMino TL, Jha V, Johansen KL, Lopes RD, Kler L, Macdougall IC, McMurray JJV, Meadowcroft AM, Obrador GT, Solomon S, Taft L, Wanner C, Waikar SS, Wheeler DC, Wiecek A, Singh AK. The ASCEND-ND trial: study design and participant characteristics. Nephrol Dial Transplant. 2022 Oct 19;37(11):2157-2170. doi: 10.1093/ndt/gfab318.
- Derived from this study: PubMed 38383961Cunningham JW, Claggett BL, Lopes RD, McMurray JJV, Perkovic V, Carroll K, Hiemstra T, Khavandi K, Lukas MA, Ranganathan P, Shannon J, van Adelsberg J, Singh AK, Solomon SD. Daprodustat and Heart Failure in CKD. J Am Soc Nephrol. 2024 May 1;35(5):607-617. doi: 10.1681/ASN.0000000000000321. Epub 2024 Feb 22.
- Derived from this study: PubMed 36565721Singh AK, McCausland FR, Claggett BL, Wanner C, Wiecek A, Atkins MB, Carroll K, Perkovic V, McMurray JJV, Wittes J, Snapinn S, Blackorby A, Meadowcroft A, Barker T, DiMino T, Mallett S, Cobitz AR, Solomon SD. Analysis of on-treatment cancer safety events with daprodustat versus conventional erythropoiesis-stimulating agents-post hoc analyses of the ASCEND-ND and ASCEND-D trials. Nephrol Dial Transplant. 2023 Jul 31;38(8):1890-1897. doi: 10.1093/ndt/gfac342.
- Derived from this study: PubMed 36005278Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
574 sites in 39 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daprodustat, Darbepoetin alfa and Iron Therapy in people with Anaemia, run by GlaxoSmithKline at 574 sites in 39 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 574 sites in United States, India, South Korea, Mexico, United Kingdom and 34 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis) (time frame: Up to 4.3 person-years for CV follow-up time period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02876835, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.