Last updated: 07/17/2024 17:20:53
Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel Prolyl hydroxylase inhibitor (PHI) Daprodustat-Three-times weekly dosing in Dialysis (ASCEND-TD)
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Mean change in Hemoglobin (Hgb) between Baseline and over Evaluation period [EP] (Weeks 28 to 52)
Timeframe: Baseline and up to Week 52
Secondary outcomes:
Mean monthly intravenous (IV) iron dose per subject up to Week 52
Timeframe: Up to Week 52
Number of subjects with adverse events (AEs), serious adverse events (SAEs), adverse event of special interest (AESI) and MACE
Timeframe: Up to Week 52
Percentage of time Hgb will be in the analysis range (10 to 11.5 grams/deciliter) over EP (Weeks 28 to 52)
Timeframe: Weeks 28 to 52
Time to stopping study treatment due to meeting rescue criteria
Timeframe: Up to Week 52
Number of responders in the Hgb analysis range over EP (Weeks 28 to 52)
Timeframe: Weeks 28 to 52
Change from Baseline in SBP, DBP and mean arterial pressure (MAP) at Week 52 and at the end of study treatment
Timeframe: Baseline and Week 52
Number of BP exacerbation events per 100 subject years
Timeframe: Up to Week 52
Number of subjects with at least one BP exacerbation event during the study
Timeframe: Up to Week 52
Pre-dose trough concentration (Ctau) of daprodustat
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M2
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M4
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M3
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M5
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M6
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Pre-dose Ctau of metabolites M13
Timeframe: Pre-dose at any one post-Baseline visit between Week 8 and Week 52
Maximum observed concentration (Cmax) of daprodustat
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours
Cmax of metabolites M2
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Cmax of metabolites M3
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Cmax of metabolites M4
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Cmax of metabolites M5
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Cmax of metabolites M6
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Cmax of metabolites M13
Timeframe: Pre-dose and 0.5, 1, 2, 3 hours post-dose
Change from Baseline in Patient Global Impression of Severity (PGI-S) score
Timeframe: Baseline and up to Week 52
Absolute values over time for composite of hematology parameters as a measure of safety
Timeframe: Up to Week 52
Changes from baseline over time in composite of hematology parameters as a measure of safety
Timeframe: Up to Week 52
Absolute values over time for composite of chemistry parameters as a measure of safety
Timeframe: Up to Week 52
Changes from baseline over time in composite of chemistry parameters as a measure of safety
Timeframe: Up to Week 52
Absolute values of systolic and diastolic blood pressure as a measure of safety
Timeframe: Up to Week 52
Change from Baseline in systolic and diastolic blood pressure as a measure of safety
Timeframe: Up to Week 52
Absolute values for heart rate as a measure of safety
Timeframe: Up to Week 52
Change from Baseline in Heart rate as a measure of safety
Timeframe: Up to Week 52
Interventions:
Drug: Daprodustat tablets
Drug: Matching placebo tablets
Drug: Epoetin alfa vials
Drug: Saline vials or bags
Enrollment:
407
Observational study model:
Not applicable
Primary completion date:
2020-19-06
Time perspective:
Not applicable
Clinical publications:
Daniel W. Coyne, Ajay K. Singh, Renato D. Lopes, Christine K. Bailey, Tara L. DiMino, Chun Huang, Jeffrey Connaire, Anjay Rastogi, Sung-Gyun Kim, Marcelo Orias, Sapna Shah, Vickas Patel, Alexander R. Cobitz, Christoph Wanner. Three-Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients. Clin J Am Soc Nephrol. 2022;
DOI: https://doi.org/10.2215/CJN.00550122
PMID: NULL
Medical condition
Anaemia
Product
GSK584430, daprodustat
Collaborators
Not applicable
Study date(s)
September 2018 to June 2020
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 99 years
Accepts healthy volunteers
No
- 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).
- Planned living-related or living-unrelated kidney transplant within 52 weeks after randomization (Day 1).
- Ferritin: <=100 nanograms/milliliter (<=100 micrograms/liter), at screening.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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).
- 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 location(s)
Location
GSK Investigational Site
Albuquerque, New Mexico, United States, 87109
Status
Study Complete
Location
GSK Investigational Site
Alexandria, Virginia, United States, 22304
Status
Study Complete
Location
GSK Investigational Site
Anyang-Si, Gyeonggi-do, South Korea, 14068
Status
Study Complete
Location
GSK Investigational Site
Belo Horizonte, Minas Gerais, Brazil, 30150-221
Status
Study Complete
Location
GSK Investigational Site
College Point, New York, United States, 11356
Status
Study Complete
Location
GSK Investigational Site
Fresno, California, United States, 93720
Status
Study Complete
Location
GSK Investigational Site
Goyang-si, Gyeonggi-do, South Korea, 10326
Status
Study Complete
Location
GSK Investigational Site
Hampton, Virginia, United States, 23666
Status
Study Complete
Location
GSK Investigational Site
Hollywood, Florida, United States, 33024
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Missouri, United States, 64111
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90025
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
Middlebury, Connecticut, United States, 06762
Status
Study Complete
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23510
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73116
Status
Study Complete
Location
GSK Investigational Site
Paramount, California, United States, 90723
Status
Study Complete
Location
GSK Investigational Site
Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
Status
Study Complete
Location
GSK Investigational Site
Pergamino, Buenos Aires, Argentina, B2700CPM
Status
Study Complete
Location
GSK Investigational Site
Pittsfield, Massachusetts, United States, 01201
Status
Study Complete
Location
GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
Status
Study Complete
Location
GSK Investigational Site
Sanlúcar de Barrameda (Cádiz), Spain, 11540
Status
Study Complete
Location
GSK Investigational Site
Sao Jose do Rio Preto, São Paulo, Brazil, 15090-000
Status
Study Complete
Location
GSK Investigational Site
Sarandi, Buenos Aires, Argentina, B1872EEB
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 04039-000
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2020-19-06
Actual study completion date
2020-19-06
Plain language summaries
Summary of results in plain language
Available language(s): English
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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