AnemiaPhase 3NCT02892149

Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Dialysis-dependent Chronic Kidney Disease (DD-CKD)

A Phase 3 study testing Vadadustat and Darbepoetin alfa in people with Anemia and Dialysis-Dependent Chronic Kidney Disease, run by Akebia Therapeutics at 278 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with dialysis-dependent chronic kidney disease (DD-CKD) Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Anemia, Dialysis-Dependent Chronic Kidney Disease
What is being tested?: Vadadustat and Darbepoetin alfa
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3,554 participants
Where: 278 sitesin 18 countries
Study dates: Aug 2016to 30 Mar 2020
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

≥18 years of age
Receiving chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease for at least 12 weeks prior to Screening
Currently maintained on erythropoiesis-stimulating agent therapy, with a dose received within 6 weeks prior to or during Screening
Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US
Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

Who cannot join

Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
Uncontrolled hypertension
Red blood cell transfusion within 8 weeks prior to randomization
Anticipated to recover adequate kidney function to no longer require dialysis
Severe heart failure at Screening (New York Heart Association Class IV)
Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening
Hypersensitivity to Vadadustat, Darbepoetin alfa, or any of their excipients

Trial locations and contacts

278 sites in 18 countries.

Country

City, postcode or hospital

278 sites in 18 countries

United States127 sites

Research Site
Albuquerque, New Mexico, 87109
Research Site
Anaheim, California, 92801
Research Site
Arlington, Texas, 76015
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Arvada, Colorado, 80002
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Asheville, North Carolina, 28801
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Astoria, New York, 11102
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Augusta, Georgia, 30904
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Austin, Texas, 78705
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Austin, Texas, 78751
Research Site
Austin, Texas, 78758
Research Site #1
Bakersfield, California, 93309
Research Site #2
Bakersfield, California, 93309
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Bradenton, Florida, 34209
Research Site
Canyon Country, California, 91387
Research Site #1
Charlotte, North Carolina, 28204
Research Site #2
Charlotte, North Carolina, 28204
Research Site #1
Chattanooga, Tennessee, 37408
Research Site #2
Chattanooga, Tennessee, 37408
Research Site
Chula Vista, California, 91910
Research Site #1
Columbus, Georgia, 31904
Research Site #2
Columbus, Georgia, 31904
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Columbus, Mississippi, 39705
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Coral Gables, Florida, 33134
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Coral Springs, Florida, 33065
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Coral Springs, Florida, 33071
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Dallas, Texas, 75231
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Dallas, Texas, 75235
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Denver, Colorado, 80230
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Detroit, Michigan, 48202
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Downey, California, 90240
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Duncanville, Texas, 75137
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Durham, North Carolina, 27704
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El Centro, California, 92243
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El Paso, Texas, 77429
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Escondido, California, 92025
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Fairfield, California, 94534
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Flushing, New York, 11355
Research Site
Fort Wayne, Indiana, 46804
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Gallup, New Mexico, 87301
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Glendale, California, 91206
Research Site #1
Granada Hills, California, 91344
Research Site #2
Granada Hills, California, 91344
Research Site
Great Neck, New York, 11021
Research Site
Greenville, North Carolina, 27834
Research Site
Greenville, Texas, 75402
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Hampton, Virginia, 23666
Research Site
Hollywood, Florida, 33024
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Houston, Texas, 77030
Research Site
Houston, Texas, 77054
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Houston, Texas, 77099
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Huntsville, Alabama, 35805
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Kansas City, Missouri, 64111
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Knoxville, Tennessee, 37923
Research Site
La Habra, California, 90631
Research Site
La Mesa, California, 91942
Research Site
Lakewood, California, 90712-2512
Research Site #1
Lauderdale Lakes, Florida, 33313
Research Site #1
Lawrenceville, Georgia, 30046
Research Site #2
Lawrenceville, Georgia, 30046
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Long Beach, California, 90807
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Long Beach, California, 90813
Research Site
Long Beach, California, 92886
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Los Angeles, California, 90022
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Manassas, Virginia, 20110
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McAllen, Texas, 78503
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Meridian, Idaho, 83642
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Merrillville, Indiana, 46410
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Mesa, Arizona, 85210
Research Site
Miami, Florida, 33125
AMPM Research Clinic
Miami, Florida, 33145
Research Site
Miami, Florida, 33150
Research Site
Miami, Florida, 33173
Research Site
Miami Beach, Florida, 33140
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Monroe, Louisiana, 71201
Research Site #1
Montebello, California, 90640
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Monterey Park, California, 91754
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Nashville, Tennessee, 37205
Research Site #1
New Bern, North Carolina, 28562
Research Site #2
New Bern, North Carolina, 28562
Research Site
New York, New York, 10010
Research Site
New York, New York, 10016
Research Site
Newhall, California, 91321
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Norfolk, Virginia, 23502
Research Site #1
Northridge, California, 91324
Research Site #2
Northridge, California, 91324
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Ocala, Florida, 34471
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Pembroke Pines, Florida, 33026
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Philadelphia, Pennsylvania, 19106
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Pine Bluff, Arkansas, 71603
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Pontiac, Michigan, 48341
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Port Huron, Michigan, 91344
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Providence, Rhode Island, 02903
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Riverside, California, 92503
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Riverside, California, 92505
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Roseville, California, 95661
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Roseville, Michigan, 48066
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Roswell, Georgia, 30076
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Sacramento, California, 95825
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San Antonio, Texas, 78202
Research Site
San Antonio, Texas, 78207
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San Antonio, Texas, 78212-4740
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San Antonio, Texas, 78221
Research Site #2
San Antonio, Texas, 78229
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San Antonio, Texas, 78251
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San Diego, California, 92111
Research Site
San Diego, California, 92115
Research Site #1
San Dimas, California, 91773
Research Site #2
San Dimas, California, 91773
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Santa Fe, New Mexico, 87505
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Shreveport, Louisiana, 71101
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Simi Valley, California, 93065
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South Burlington, Vermont, 05403
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Springfield, Massachusetts, 01107
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St Louis, Missouri, 63136
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St. George, Utah, 84790
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Stamford, Connecticut, 06902
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Statesboro, Georgia, 30458
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Takoma Park, Maryland, 20912
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Tampa, Florida, 33614
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Tarzana, California, 91356
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The Bronx, New York, 10461
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Westminster, Colorado, 80031
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Whittier, California, 90603
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Whittier, California, 90606
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Winston-Salem, North Carolina, 27103
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Winter Park, Florida, 32789
Research Site
Yonkers, New York, 10710

Other trials in United States

Brazil25 sites

Research Site
Belo Horizonte, Minas Gerais, 30130-100
Research Site
Belo Horizonte, Minas Gerais, 30150-221
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Canoas, Rio Grande do Sul, 92425-900
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Criciúma, Santa Catarina, 88801-250
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Curitiba, Paraná, 80010-030
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Feira de Santana, Estado de Bahia, 44001-584
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Fortaleza, Ceará, 60430-370
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Itabuna, Estado de Bahia, 45600-625
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Joinville, Santa Catarina, 89202-050
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Juiz de Fora, Minas Gerais, 36025-330
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Juiz de Fora, Minas Gerais, 36036-330
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Maringá, Paraná, 87060-040
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Passo Fundo, Rio Grande do Sul, 99010-080
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Porto Alegre, Rio Grande do Sul, 90035-074
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Porto Alegre, Rio Grande do Sul, 90035-903
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Porto Alegre, Rio Grande do Sul, 90160-093
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Porto Alegre, Rio Grande do Sul, 90610-000
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Santo André, São Paulo, 09080-110
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Santo André, São Paulo, 09090-790
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São Bernardo do Campo, São Paulo, 09715-090
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São José do Rio Preto, São Paulo, 15015-200
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São Paulo, São Paulo, 01232-010
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São Paulo, São Paulo, 04039-000
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São Paulo, São Paulo, 05403-000
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Vitória, Espírito Santo, 29055-450

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Bulgaria17 sites

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Byala, 7100
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Cherven Bryag, 5980
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Dobrich, 9300
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Dupnitsa, 2600
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Haskovo, 6300
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Plovdiv, 4002
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Rousse, 7002
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Shumen, 9700
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Silistra, 7500
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Sliven, 8800
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Sofia, 1233
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Sofia, 1407
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Sofia, 1750
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Varna, 9002
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Veliko Tarnovo, 5000
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Vidin, 3700
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Vratsa, 3000

Other trials in Bulgaria

South Korea14 sites

Research Site
Bucheon-si, Gyeonggi-do, 14647
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Busan, 47392
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Busan, 49201
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Chuncheon, Gangwon-do, 200-702
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Goyang-si, Gyeonggi-do, 10380
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Goyang-si, Gyeonggi-do, 10444
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Guri-si, Gyeonggi-do, 11923
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Seongnam-si, Gyeonggi-do, 13496
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Seoul, 2841
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Seoul, 3080
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Seoul, 6351
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Seoul, 6591
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Seoul, 7345
Research Site
Suwon, Gyeonggi-do, 16247

Other trials in South Korea

Russia12 sites

Research Site #2
Kemerovo, 650066
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Moscow, 123182
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Moscow, 125466
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Nizhny Novgorod, 603001
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Nizhny Novgorod, 603076
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Novorossiysk, 353915
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Saint Petersburg, 195067
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Saint Petersburg, 197022
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Saint Petersburg, 197110
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Saint Petersburg, 198205
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Saint Petersburg, 199004
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Yekaterinburg, 620102

Other trials in Russia

Ukraine12 sites

Research Site
Brovary, 7400
Research Site #1
Cherkassy, 18009
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Dnipro, 49005
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Ivano-Frankivsk, 76008
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Kharkiv, 61037
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Kyiv, 2125
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Mykolaiv, 54058
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Ternopil, 46002
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Uzhhorod, 88018
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Vinnytsia, 21018
Research Site
Zaporizhzhya, 69600
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Zhytomyr, 10002

Other trials in Ukraine

Argentina9 sites

Research Site
Ciudad Autonoma Buenos Aires, Buenos Aires, C1181ACH
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Córdoba, 5000
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Córdoba, X5000EVQ
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Corrientes, 3400
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Junín, Buenos Aires, 6000
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Pergamino, Buenos Aires, B2700CPM
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Salta, A4400AXO
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San Luis, 5700
Research Site
Sarandí, Buenos Aires, B1872EEA

Other trials in Argentina

Australia8 sites

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Box Hill, Victoria, 3128
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Cairns, Queensland, 4870
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Fitzroy, Victoria, 3065
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Launceston, Tasmania, 7250
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Liverpool, New South Wales, 2170
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Nedlands, Western Australia, 6009
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New Lambton Heights, New South Wales, 2305
Research Site
Wahroonga, New South Wales, 2076

Other trials in Australia

Poland7 sites

Research Site
Biała Podlaska, 21-500
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Golub-Dobrzyń, 87-400
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Kołobrzeg, 78-100
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Lodz, 90-153
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Lodz, 92-213
Research Site
Lodz, 93-338
Research Site
Warsaw, 04-749

Other trials in Poland

Serbia7 sites

Research Site #1
Belgrade, 11000
Research Site #2
Belgrade, 11000
Research Site #3
Belgrade, 11000
Research Site #4
Belgrade, 11000
Research Site
Kragujevac, 34000
Research Site
Niš, 18000
Research Site
Zaječar, 19000

Other trials in Serbia

Canada6 sites

Research Site
Greater Sudbury, Ontario, P3E 5J1
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Greenfield Park, Quebec, J4V 2H1
Research Site
Halifax, Nova Scotia, B3H 2Y0
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Montreal, Quebec, H2X 3J4
Research Site
Oshawa, Ontario, L1H 1B9
Research Site
Sydney, Nova Scotia, B1P 1P3

Other trials in Canada

France6 sites

Research Site
Bordeaux, Gironde, 33300
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Marseille, Bouches-du-Rhône, 13005
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Paris, 75015
Research Site
Paris, 75020
Research Site
Reims, Marne, 51092
Research Site
Saint-Priest-En-Jarez, Pays de la Loire Region, 42055

Other trials in France

Israel6 sites

Research Site
Ashkelon, 78278
Research Site
Haifa, 3109601
Research Site
Haifa, 34362
Research Site
Jerusalem, 91031
Research Site
Kfar Saba, 4428164
Research Site
Rishon LeZiyyon, 75141

Other trials in Israel

Italy6 sites

Research Site
Bari, 70124
Research Site
Genova, 16132
Research Site
Lecco, 23900
Research Site
Pavia, 27100
Research Site
Roma, 168
Research Site
Siena, 53100

Other trials in Italy

United Kingdom5 sites

Research Site
Cambridge, Cambridgeshire, CB2 0QQ
Research Site
Doncaster, South Yorkshire, DN2 5LT
Research Site
Kettering, Leicestershire, NN16 8DB
Research Site
London, Greater London, SE5 9RS
Research Site
Stevenage, Hertfordshire, SG1 4AB

Other trials in United Kingdom

Germany4 sites

Research Site
Berlin, 10117
Research Site
Düsseldorf, North Rhine-Westphalia, 40210
Research Site
Rostock, Mecklenburg-Vorpommern, 18057
Research Site
Villingen-Schwenningen, Baden-Wurttemberg, 78054

Other trials in Germany

Mexico4 sites

Research Site
Culiacán, Sinaloa, 80230
Research Site
Morelia, Michoacán, 58260
Research Site
Pachuca, Hidalgo, 42070
Research Site
Zapopan, Jalisco, 45030

Other trials in Mexico

Portugal3 sites

Research Site
Beja, 7800-309
Research Site
Leiria, 2400-441
Research Site
Loures, 2674-514

Other trials in Portugal

About this study

Official title: Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE-CONVERSION)

A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with dialysis-dependent chronic kidney disease (DD-CKD)

Read the detailed description

This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the maintenance treatment of anemia in participants with DD-CKD

Conditions: Anemia, Dialysis-Dependent Chronic Kidney Disease
Being tested: Vadadustat, Darbepoetin alfa
Keywords: AKB-6548, Chronic kidney disease, anemia, CKD, chronic renal insufficiency, renal impairment, erythropoietin, kidney, renal, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor prolyl-hydroxylase inhibitor, HIF-PHI, efficacy, safety, Phase 3, cardiovascular, DD-CKD
Medical subject headings: Anemia, Renal Insufficiency, Chronic, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VadadustatDrug
Also called AKB-6548
Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Darbepoetin alfaDrug
Also called Aranesp
Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.

Study groups in NCT02892149
Study group	Role	What they receive
Vadadustat	Experimental	Not described Receives: Drug: Vadadustat
Darbepoetin alfa	Active comparator	Not described Receives: Drug: Darbepoetin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates.
Measured: Baseline; Weeks 24 to 36
Median Time to First Major Adverse Cardiovascular Event (MACE)
MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
Measured: Up to 170 weeks

Secondary outcomes (5)

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates.
Measured: Baseline; Weeks 40 to 52
Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis
MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
Measured: Up to 170 weeks
Median Time to First Cardiovascular MACE
MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
Measured: Up to 170 weeks
Median Time to First Cardiovascular Death
Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
Measured: Up to 170 weeks
Median Time to First All-cause Mortality
Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.
Measured: Up to 170 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 201630 Mar 2020

First posted8 Sep 2016 (estimated)
Study startAug 2016
Primary completion16 Jan 2020
Study completion30 Mar 2020

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 (4)Papers the sponsor has linked to this study.
Other trials for AnemiaStudies of the same condition, open and under way.
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: 3,554 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02892149
Sponsor's protocol ID: AKB-6548-CI-0017
Other IDs: 2016-001360-11, 2016
Status last verified: Jun 2022
First submitted: 2 Sep 2016
Last updated: 28 Jun 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Chertow GM, Eckardt KU, Sarnak MJ, Winkelmayer WC, Agarwal R, Minga T, Luo W, Burke SK. Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States. J Am Soc Nephrol. 2025 Oct 1;36(10):1984-1997. doi: 10.1681/ASN.0000000708. Epub 2025 May 13.
PubMed 40359056
Sarnak MJ, Agarwal R, Boudville N, Chowdhury PCP, Eckardt KU, Gonzalez CR, Kooienga LA, Koury MJ, Ntoso KA, Luo W, Parfrey PS, Vargo DL, Winkelmayer WC, Zhang Z, Chertow GM. Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrol Dial Transplant. 2023 Sep 29;38(10):2358-2367. doi: 10.1093/ndt/gfad074.
PubMed 37096396
Natale 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
Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.
PubMed 33913638

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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RecruitingObservational study
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All Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE-CONVERSION)
ClinicalTrials.gov ID: NCT02892149
Acronym / sponsor ID: AKB-6548-CI-0017
Conditions: Anemia, Dialysis-Dependent Chronic Kidney Disease
Keywords: AKB-6548, Chronic kidney disease, anemia, CKD, chronic renal insufficiency, renal impairment, erythropoietin, kidney
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,554 participants (actual)
Lead sponsor: Akebia TherapeuticsIndustry (pharma, biotech, devices)
Study start: Aug 2016 (actual)
Primary completion: 16 Jan 2020 (actual)
Study completion: 30 Mar 2020 (actual)
First posted: 8 Sep 2016 (estimated)
Results: Posted 28 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with dialysis-dependent chronic kidney disease (DD-CKD)

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Vadadustat	Experimental	Drug: Vadadustat
Darbepoetin alfa	Active comparator	Drug: Darbepoetin alfa

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

≥18 years of age
Receiving chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease for at least 12 weeks prior to Screening
Currently maintained on erythropoiesis-stimulating agent therapy, with a dose received within 6 weeks prior to or during Screening
Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US
Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

Key exclusion criteria (7 listed)

Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
Uncontrolled hypertension
Red blood cell transfusion within 8 weeks prior to randomization
Anticipated to recover adequate kidney function to no longer require dialysis
Severe heart failure at Screening (New York Heart Association Class IV)

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
VadadustatAlso: AKB-6548Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.	Drug	Vadadustat
Darbepoetin alfaAlso: AranespSubcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.	Drug	Darbepoetin alfa

Primary outcome

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
Time frame: Baseline; Weeks 24 to 36
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates.
Median Time to First Major Adverse Cardiovascular Event (MACE)
Time frame: Up to 170 weeks
MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

5 secondary outcomes

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)
Time frame: Baseline; Weeks 40 to 52
Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis
Time frame: Up to 170 weeks
Median Time to First Cardiovascular MACE
Time frame: Up to 170 weeks
Median Time to First Cardiovascular Death
Time frame: Up to 170 weeks
Median Time to First All-cause Mortality
Time frame: Up to 170 weeks

Results and safety

Results posted to the registry on 28 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vadadustat	1,777	1,425
Darbepoetin Alfa	1,777	1,421

Primary outcome: Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

Time frame: Baseline; Weeks 24 to 36. Least squares mean (Standard Error). Unit: Grams per deciliter (g/dL)

Measure	Vadadustat n = 1777	Darbepoetin Alfa n = 1777
Value	0.19 (0.032)	0.36 (0.032)

Vadadustat vs Darbepoetin Alfa: Least squares mean difference: -0.17 (95% CI -0.23 to -0.10)

Population analysed: Randomized Population: All participants randomized. Analyses of this population were based on the randomized treatment.

Primary outcome: Median Time to First Major Adverse Cardiovascular Event (MACE)

Time frame: Up to 170 weeks. Median (Inter-Quartile Range). Unit: Weeks

Measure	Vadadustat n = 333	Darbepoetin Alfa n = 353
Value	48.86 (26.43 to 79.71)	48.00 (22.43 to 75.57)

Vadadustat vs Darbepoetin Alfa: Hazard Ratio (HR): 0.96 (95% CI 0.828 to 1.117), p = 0.4745, Log Rank
Vadadustat vs Darbepoetin Alfa: Hazard Ratio (HR): 0.96 (95% CI 0.833 to 1.113), p =0.4877, Log Rank

Population analysed: Safety Population (INNO2VATE): All participants from the INNO2VATE population who received 1 or more doses of study drug. Only those participants with MACE events were analyzed for this outcome measure.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 170 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vadadustat	973 of 1,768 (55%)	964 of 1,768 (54.5%)	276 of 1,768
Darbepoetin Alfa	1,032 of 1,769 (58.3%)	993 of 1,769 (56.1%)	290 of 1,769

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40359056Chertow GM, Eckardt KU, Sarnak MJ, Winkelmayer WC, Agarwal R, Minga T, Luo W, Burke SK. Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States. J Am Soc Nephrol. 2025 Oct 1;36(10):1984-1997. doi: 10.1681/ASN.0000000708. Epub 2025 May 13.
Derived from this study: PubMed 37096396Sarnak MJ, Agarwal R, Boudville N, Chowdhury PCP, Eckardt KU, Gonzalez CR, Kooienga LA, Koury MJ, Ntoso KA, Luo W, Parfrey PS, Vargo DL, Winkelmayer WC, Zhang Z, Chertow GM. Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrol Dial Transplant. 2023 Sep 29;38(10):2358-2367. doi: 10.1093/ndt/gfad074.
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.
Derived from this study: PubMed 33913638Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.
Individual participant dataSharing planned: No

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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.

Chief Medical Officer study director

Akebia Therapeutics

278 sites in 18 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vadadustat and Darbepoetin alfa in people with Anemia and Dialysis-Dependent Chronic Kidney Disease, run by Akebia Therapeutics at 278 sites in 18 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 5 inclusion and 7 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 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 278 sites in United States, Brazil, Bulgaria, South Korea, Russia and 13 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 28 Jun 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?

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) (time frame: Baseline; Weeks 24 to 36). 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 NCT02892149, which also lists 4 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 28 Jun 2022.