AnaemiaPhase 3NCT03400033
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Three-times Weekly Dosing in Dialysis (ASCEND-TD)
A Phase 3 study testing Daprodustat tablets, Epoetin alfa vials and Saline vials or bags in people with Anaemia, run by GlaxoSmithKline at 91 sites in 13 countries.
Trial summary
This Phase 3 study in hemodialysis-dependent subjects with anemia will evaluate the efficacy and safety of daprodustat administered three-times weekly compared to epoetin alfa, the current standard of care. This study includes a 4 week Screening Period, a 52 week Treatment Period and a 4 to 6 week follow-up period. 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 tablets, Epoetin alfa vials and Saline vials or bags
- 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
- 407 participants
- Where
- 91 sitesin 13 countries
- Study dates
- 5 Sep 2018to 19 Jun 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be 18 to 99 years of age inclusive, at the time of signing the informed consent.
- Use of any approved rhEPO or analog for at least 8 weeks prior to the screening visit and continuing during the screening period until randomization (Day 1).
- Hgb concentration (measured by HemoCue) within the following range: Week -4: Hgb 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). If Hgb is 11.6 to 11.9 grams/deciliter (7.2 to 7.4 millimoles/liter), up to two retests are allowed; the retest value must be between 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). Day 1: Hgb 8 to 11 grams/deciliter (5 to 6.8 millimoles/liter) and receiving at least the minimum rhEPO or analog dose 3. Hgb>11 to 11.5 grams/deciliter (6.8 to 7.1 millimoles/liter) and receiving greater than the minimum rhEPO or analog dose 3.
- On hemodialysis (including hemofiltration or hemodiafiltration) >90 days prior to screening and continuing during the screening period.
- On hemodialysis (in-center) >=3 times per week.
- Male and female subjects are eligible. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP), or A WOCBP who agrees to follow the contraceptive guidance from at least 28 days prior to first dose of study treatment and for at least 28 days after the last dose of study treatment.
- Capable of giving signed informed consent.
- In France, a subject will be eligible for inclusion in this study if he or she is either affiliated to or beneficiary of a social security category.
Who cannot join
- Planned living-related or living-unrelated kidney transplant within 52 weeks after randomization (Day 1).
- Ferritin: <=100 nanograms/milliliter (<=100 micrograms/liter), at screening.
- Transferrin saturation (TSAT): <=20 percent, at screening. If TSAT is 18 to 20 percent, then a retest using a new blood sample can be obtained within 7 days of the final laboratory report; the final retest value must be >20 percent to confirm eligibility.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia.
- Conditions, other than anemia of CKD, which can affect erythropoiesis.
- Myocardial infarction (MI) or acute coronary syndrome within 8 weeks prior to screening through to randomization (Day 1).
Show all 18Show fewer
- Stroke or transient ischemic attack within 8 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 as determined by the investigator that would contraindicate the use of rhEPO.
- Bazett's correction of QTc interval (QTcB): at Day 1: QTcB >500 milliseconds, or QTcB >530 milliseconds in subjects with bundle branch block. There is no QTc (corrected QT) exclusion for subjects with a predominantly ventricular paced rhythm.
- Liver Disease: presence of any one of the following liver-related laboratory values or conditions, at screening, is exclusionary: ALT >2x upper limit of normal (ULN); Bilirubin >1.5x ULN; or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Evidence of actively bleeding gastric, duodenal or esophageal ulcer disease OR clinically significant gastro intestinal bleeding <= 8 weeks prior to screening through to randomization (Day 1).
- History of malignancy within 2 years prior to screening through to randomization (Day 1), currently receiving treatment for cancer, or complex kidney cyst (e.g., Bosniak Category IIF, III or IV) >3 centimeters.
- Use of a strong inhibitor of Cytochrome P4502C8 [CYP2C8] (e.g. gemfibrozil) or a strong inducer of CYP2C8 (e.g. rifampin/rifampicin).
- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (daprodustat) or epoetin alfa.
- Use of another investigational agent within 30 days or within five half-lives of the investigational agent (whichever is longer) or currently participating in a study of an investigational device prior to screening through to randomization (Day 1).
- Any prior treatment with daprodustat for treatment duration of >30 days.
- 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 rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Trial locations and contacts
91 sites in 13 countries.
91 sites in 13 countries
United States23 sites
GSK Investigational Site
Albuquerque, New Mexico, 87109
GSK Investigational Site
Alexandria, Virginia, 22304
GSK Investigational Site
College Point, New York, 11356
GSK Investigational Site
Fresno, California, 93720
GSK Investigational Site
Hampton, Virginia, 23666
GSK Investigational Site
Hollywood, Florida, 33024
GSK Investigational Site
Houston, Texas, 77004
GSK Investigational Site
Houston, Texas, 77099
GSK Investigational Site
Kansas City, Missouri, 64111
GSK Investigational Site
Los Angeles, California, 90025
GSK Investigational Site
Lufkin, Texas, 75904
GSK Investigational Site
Macon, Georgia, 31201
GSK Investigational Site
Meridian, Idaho, 83642
GSK Investigational Site
Mesa, Arizona, 85210
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Middlebury, Connecticut, 06762
GSK Investigational Site
Norfolk, Virginia, 23510
GSK Investigational Site
Oklahoma City, Oklahoma, 73116
GSK Investigational Site
Paramount, California, 90723
GSK Investigational Site
Pittsfield, Massachusetts, 01201
GSK Investigational Site
St Louis, Missouri, 63110
GSK Investigational Site
Tampa, Florida, 33614
GSK Investigational Site
Winston-Salem, North Carolina, 27103
Russia19 sites
GSK Investigational Site
Kazan', 420012
GSK Investigational Site
Kolomna, 140407
GSK Investigational Site
Krasnodar, 350029
GSK Investigational Site
Krasnogorsk, 143400
GSK Investigational Site
Mytischi, 141009
GSK Investigational Site
Novorossiysk, 353915
GSK Investigational Site
Novosibirsk, 630087
GSK Investigational Site
Omsk, 644111
GSK Investigational Site
Orenburg, 460040
GSK Investigational Site
Penza, 440034
GSK Investigational Site
Podolsk, 142110
GSK Investigational Site
Saint Petersburg, 193318
GSK Investigational Site
Saint Petersburg, 194104
GSK Investigational Site
Saint Petersburg, 194354
GSK Investigational Site
Saint Petersburg, 196247
GSK Investigational Site
Saint Petersburg, 197110
GSK Investigational Site
Saint Petersburg, 197374
GSK Investigational Site
Ufa, 450071
GSK Investigational Site
Yaroslavl, 150062
Spain8 sites
GSK Investigational Site
Almería, 04009
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
Girona, 17007
GSK Investigational Site
Granollers, Barcelona, 08041
GSK Investigational Site
Madrid, 28100
GSK Investigational Site
Manises (Valencia), 46940
GSK Investigational Site
Sanlúcar de Barrameda (Cádiz), 11540
Brazil7 sites
GSK Investigational Site
Belo Horizonte, Minas Gerais, 30150-221
GSK Investigational Site
Curitiba, Paraná, 80440-020
GSK Investigational Site
Passo Fundo, Rio Grande do Sul, 99010-080
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, 04039-000
South Korea7 sites
GSK Investigational Site
Anyang-Si, Gyeonggi-do, 14068
GSK Investigational Site
Busan, 49201
GSK Investigational Site
Goyang-si, Gyeonggi-do, 10326
GSK Investigational Site
Incheon, 405-760
GSK Investigational Site
Seoul, 07061
GSK Investigational Site
Seoul, 07441
GSK Investigational Site
Seoul, 134-727
France5 sites
GSK Investigational Site
Bayonne, 64109
GSK Investigational Site
Epagny Metz-Tessy, 74370
GSK Investigational Site
Le Mans, 72037
GSK Investigational Site
Nice, 06001
GSK Investigational Site
Strasbourg, 67000
Poland5 sites
GSK Investigational Site
Katowice, 40-027
GSK Investigational Site
Lodz, 92-213
GSK Investigational Site
Sandomierz, 27-600
GSK Investigational Site
Tarnowskie Góry, 42-612
GSK Investigational Site
Żyrardów, 96-300
Argentina4 sites
GSK Investigational Site
Mar del Plata, Buenos Aires, 7600
GSK Investigational Site
Pergamino, Buenos Aires, B2700CPM
GSK Investigational Site
Rosario, Santa Fe Province, 2000
GSK Investigational Site
Sarandí, Buenos Aires, B1872EEB
Italy4 sites
GSK Investigational Site
Bologna, Emilia-Romagna, 40138
GSK Investigational Site
Modena, Emilia-Romagna, 41124
GSK Investigational Site
Pavia, Lombardy, 27100
GSK Investigational Site
Verona, Veneto, 37126
United Kingdom4 sites
GSK Investigational Site
Bradford, BD5 0NA
GSK Investigational Site
London, SE5 9RS
GSK Investigational Site
Sheffield, S5 7AU
GSK Investigational Site
Swansea, SA6 6NL
Australia2 sites
GSK Investigational Site
Heidelberg, Victoria, 3084
GSK Investigational Site
Parkville, Victoria, 3050
Romania2 sites
GSK Investigational Site
Constanța, 900591
GSK Investigational Site
Reşiţa, 320166
About this study
Official title: A Phase 3 Randomized, Double-blind, Active-controlled, Parallel-group, Multi-center Study in Hemodialysis Participants With Anemia of Chronic Kidney Disease to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Recombinant Human Erythropoietin or Its Analogs
This Phase 3 study in hemodialysis-dependent subjects with anemia will evaluate the efficacy and safety of daprodustat administered three-times weekly compared to epoetin alfa, the current standard of care. This study includes a 4 week Screening Period, a 52 week Treatment Period and a 4 to 6 week follow-up period. Each subject will remain in the study for up to 62 weeks. Approximately 402 subjects will be randomized to receive either daprodustat three times weekly or epoetin alfa three-times weekly or once weekly, depending on dose level.
- Conditions
- Anaemia
- Being tested
- Daprodustat tablets, Matching placebo tablets, Epoetin alfa vials, Saline vials or bags
- Keywords
- CKD, EPO, rhEPO, Hemodialysis dependent, Daprodustat
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daprodustat tabletsDrug
Round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route.
Matching placebo tabletsDrug
Matching placebo to daprodustat tablets supplied as round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route.
Epoetin alfa vialsDrug
Single-dose, preservative-free vials in unit dose strengths of 2000, 3000, 4000 and 10,000 Units/milliliter administered by the IV route.
Saline vials or bagsDrug
0.9% sodium chloride saline vials or bags administered by the IV route.
| Study group | Role | What they receive |
|---|---|---|
| Daprodustat | Experimental | Subjects randomized to this arm will receive daprodustat tablets titrated doses from 2 to 48 milligrams orally three-times weekly along with saline by IV route for the 52 weeks treatment period. Receives: Drug: Daprodustat tablets; Drug: Saline vials or bags |
| Epoetin alfa | Active comparator | Subjects randomized to this arm will receive matching placebo tablets to daprodustat orally three-times weekly and Epoetin alfa by IV route for the 52 weeks treatment period. Receives: Drug: Matching placebo tablets; Drug: Epoetin alfa vials |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Hemoglobin Levels Over the Evaluation Period (Week 28 to Week 52)
Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.
Measured: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary outcomes (12)
Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant
Average monthly IV iron dose (mg) per participant during Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from Day 1 to Week 52 while the participant was on study treatment and dividing by (the number of days the participant was on study treatment divided by 30.4375 days). Analysis was performed using the ANCOVA model with terms for treatment, Baseline monthly IV iron dose, and region.
Measured: Day 1 to Week 52
Change From Baseline in Hemoglobin Levels at Week 52
Blood samples were collected from participants for hemoglobin measurements. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the post-randomization visit value minus Baseline value. Analysis was performed using a mixed model repeated measures (MMRM) model fitted to hemoglobin data collected after Baseline up to Week 52, excluding values collected during the stabilization period (Day 1 to Week 28). The model included factors for treatment, time, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interaction terms.
Measured: Baseline (Pre-dose on Day 1) and Week 52
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Participants received treatment during the study to achieve or maintain hemoglobin level in the target range. Percentage of time for which hemoglobin level was maintained within the analysis range (10 to 11.5 grams/deciliter) has been presented.
Measured: Week 28 to Week 52
Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled hemoglobin values that were taken during this time period. Hemoglobin responders were defined as the number of participants with a mean hemoglobin during the evaluation period that falls within the hemoglobin analysis range of 10-11.5 grams/deciliter.
Measured: Week 28 to Week 52
Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria
Percentage of participants permanently stopping study treatment due to meeting rescue criteria has been presented.
Measured: Up to Week 52
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52
Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the on-treatment visit value minus Baseline value. Analysis was performed using MMRM model with treatment group, time, region, Baseline value, Baseline value*time, treatment group*time as variables.
Measured: Baseline (Week -4 ) and Week 52
Change From Baseline in SBP, DBP and MAP at End of Treatment
Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the last on-treatment visit value minus Baseline value. Analysis was performed using ANCOVA model with terms for treatment group, region and Baseline value. Adjusted mean and standard error have been presented.
Measured: Baseline (Week -4) and end of treatment (last on-treatment value until Week 52)
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
BP exacerbation event is defined (based on post-dialysis BP) as SBP >=25 mmHg increased from Baseline or SBP >=180 mmHg; or 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.
Measured: Up to 52 weeks
Number of Participants With at Least One BP Exacerbation Event During the Study
BP exacerbation (based on post-dialysis BP) is defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180mmHg; or DBP >=15 mmHg increase from Baseline or DBP >=110 mmHg. Number of participants with at least 1 BP exacerbation event have been reported.
Measured: Up to 52 weeks
Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S)
The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity of their anemia of Chronic kidney disease (CKD). It is measured on a 5-point disease severity scale ranging from 0 (absent) to 4 (very severe), higher score indicates more disease severity. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline in on-treatment PGI-S scores was defined as the on-treatment visit value minus Baseline value. Analysis was performed using MMRM model fitted from Baseline up to Week 52 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
Measured: Baseline (Pre-dose on Day 1) and Weeks 8, 12, 28, 52
Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13).
Measured: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13).
Measured: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 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 posted17 Jan 2018
- Study start5 Sep 2018
- Primary completion19 Jun 2020
- Study completion19 Jun 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 (2)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
- Model description
- Subjects will be randomized to receive either daprodustat or epoetin alfa in a parallel manner. .
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 407 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
- NCT03400033
- Sponsor's protocol ID
- 204837
- Other IDs
- 2017-004372-56, 2017
- Status last verified
- Jun 2021
- First submitted
- 8 Jan 2018
- Last updated
- 12 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
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 36005278Coyne DW, Singh AK, Lopes RD, Bailey CK, DiMino TL, Huang C, Connaire J, Rastogi A, Kim SG, Orias M, Shah S, Patel V, Cobitz AR, Wanner C. Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients: ASCEND-TD: A Phase 3 Randomized, Double-Blind, Noninferiority Trial. Clin J Am Soc Nephrol. 2022 Sep;17(9):1325-1336. doi: 10.2215/CJN.00550122. Epub 2022 Aug 2.
PubMed 35918106
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Double-blind, Active-controlled, Parallel-group, Multi-center Study in Hemodialysis Participants With Anemia of Chronic Kidney Disease to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Recombinant Human Erythropoietin or Its Analogs
- ClinicalTrials.gov ID
- NCT03400033
- Acronym / sponsor ID
- 204837
- Conditions
- Anaemia
- Keywords
- CKD, EPO, rhEPO, Hemodialysis dependent, Daprodustat
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 407 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2018 (actual)
- Primary completion
- 19 Jun 2020 (actual)
- Study completion
- 19 Jun 2020 (actual)
- First posted
- 17 Jan 2018 (actual)
- Results
- Posted 12 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 3 study in hemodialysis-dependent subjects with anemia will evaluate the efficacy and safety of daprodustat administered three-times weekly compared to epoetin alfa, the current standard of care. This study includes a 4 week Screening Period, a 52 week Treatment Period and a 4 to 6 week follow-up period. Each subject will remain in the study for up to 62 weeks. Approximately 402 subjects will be randomized to receive either daprodustat three times weekly or epoetin alfa three-times weekly or once weekly, depending on dose level.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized to receive either daprodustat or epoetin alfa in a parallel manner. .
| Arm | Type | Receives |
|---|---|---|
| Daprodustat | Experimental | Drug: Daprodustat tablets, Drug: Saline vials or bagsSubjects randomized to this arm will receive daprodustat tablets titrated doses from 2 to 48 milligrams orally three-times weekly along with saline by IV route for the 52 weeks treatment period. |
| Epoetin alfa | Active comparator | Drug: Matching placebo tablets, Drug: Epoetin alfa vialsSubjects randomized to this arm will receive matching placebo tablets to daprodustat orally three-times weekly and Epoetin alfa by IV route for the 52 weeks treatment period. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject must be 18 to 99 years of age inclusive, at the time of signing the informed consent.
- Use of any approved rhEPO or analog for at least 8 weeks prior to the screening visit and continuing during the screening period until randomization (Day 1).
- Hgb concentration (measured by HemoCue) within the following range: Week -4: Hgb 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). If Hgb is 11.6 to 11.9 grams/deciliter (7.2 to 7.4 millimoles/liter), up to two retests are allowed; the retest value must be between 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). Day 1: Hgb 8 to 11 grams/deciliter (5 to 6.8 millimoles/liter) and receiving at least the minimum rhEPO or analog dose 3. Hgb>11 to 11.5 grams/deciliter (6.8 to 7.1 millimoles/liter) and receiving greater than the minimum rhEPO or analog dose 3.
- On hemodialysis (including hemofiltration or hemodiafiltration) >90 days prior to screening and continuing during the screening period.
- On hemodialysis (in-center) >=3 times per week.
Key exclusion criteria (18 listed)
- Planned living-related or living-unrelated kidney transplant within 52 weeks after randomization (Day 1).
- Ferritin: <=100 nanograms/milliliter (<=100 micrograms/liter), at screening.
- Transferrin saturation (TSAT): <=20 percent, at screening. If TSAT is 18 to 20 percent, then a retest using a new blood sample can be obtained within 7 days of the final laboratory report; the final retest value must be >20 percent to confirm eligibility.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia.
- Conditions, other than anemia of CKD, which can affect erythropoiesis.
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 |
|---|---|---|
| Daprodustat tabletsRound, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route. | Drug | Daprodustat |
| Matching placebo tabletsMatching placebo to daprodustat tablets supplied as round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route. | Drug | Epoetin alfa |
| Epoetin alfa vialsSingle-dose, preservative-free vials in unit dose strengths of 2000, 3000, 4000 and 10,000 Units/milliliter administered by the IV route. | Drug | Epoetin alfa |
| Saline vials or bags0.9% sodium chloride saline vials or bags administered by the IV route. | Drug | Daprodustat |
Primary outcome
Mean Change From Baseline in Hemoglobin 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 hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.
12 secondary outcomes
Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant
Time frame: Day 1 to Week 52
Change From Baseline in Hemoglobin Levels at Week 52
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Time frame: Week 28 to Week 52
Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Time frame: Week 28 to Week 52
Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria
Time frame: Up to Week 52
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52
Time frame: Baseline (Week -4 ) and Week 52
Change From Baseline in SBP, DBP and MAP at End of Treatment
Time frame: Baseline (Week -4) and end of treatment (last on-treatment value until Week 52)
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
Time frame: Up to 52 weeks
Number of Participants With at Least One BP Exacerbation Event During the Study
Time frame: Up to 52 weeks
Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S)
Time frame: Baseline (Pre-dose on Day 1) and Weeks 8, 12, 28, 52
Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Time frame: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Time frame: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 35918106Coyne DW, Singh AK, Lopes RD, Bailey CK, DiMino TL, Huang C, Connaire J, Rastogi A, Kim SG, Orias M, Shah S, Patel V, Cobitz AR, Wanner C. Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients: ASCEND-TD: A Phase 3 Randomized, Double-Blind, Noninferiority Trial. Clin J Am Soc Nephrol. 2022 Sep;17(9):1325-1336. doi: 10.2215/CJN.00550122. Epub 2022 Aug 2.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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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
91 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daprodustat tablets, Epoetin alfa vials and Saline vials or bags in people with Anaemia, run by GlaxoSmithKline at 91 sites in 13 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 8 inclusion and 18 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 12 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 91 sites in United States, Russia, Spain, Brazil, South Korea and 8 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 12 Jul 2021). 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?
Mean Change From Baseline in Hemoglobin 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)). 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 NCT03400033, which also lists 2 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 12 Jul 2021.