Last updated: 07/17/2024 17:02:12
Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Dialysis (ASCEND-D)
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A phase 3 randomized, open-label (sponsor-blind), active-controlled, parallel-group, multi-center, event driven study in dialysis subjects with anemia associated with chronic kidney disease to evaluate the safety and efficacy of daprodustat compared to recombinant human erythropoietin, following a switch from erythropoietin-stimulating agents
Trial description: The purpose of this multi-center event-driven study in participants with anemia associated with chronic kidney disease (CKD) to evaluate the safety and efficacy of daprodustat.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Time to the first occurrence of adjudicated major adverse cardiovascular event (MACE) (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke)
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Mean change in hemoglobin (Hgb) between Baseline and efficacy period (EP) (mean over Weeks 28-52)
Timeframe: Baseline and up to and including Week 52
Secondary outcomes:
Time to first occurrence of adjudicated MACE
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of adjudicated MACE or a thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism)
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of adjudicated MACE or a hospitalization for heart failure (HF)
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Average monthly intravenous (IV) iron dose milligram (mg) per subject to Week 52
Timeframe: Up to and including Week 52
Time to first occurrence of all-cause mortality, cardiovascular (CV) mortality, fatal or non-fatal MI, fatal or non-fatal stroke
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of MACE or hospitalization for HF (recurrent events analysis)
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of CV death or non fatal MI incidences
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of all-cause hospitalization
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of all cause hospital re-admission within 30 days
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of MACE or hospitalization for HF or thromboembolic events
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of Hospitalization for HF
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to first occurrence of Thromboembolic events
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Hgb change from Baseline to Week 52
Timeframe: Baseline, and up to and including Week 52
Percentage of responders, defined as mean Hgb within Hgb analysis range
Timeframe: Up to and including Week 52
Number of responders, defined as mean Hgb within Hgb analysis range
Timeframe: Up to and including Week 52
Percentage time for which Hgb is in analysis range during the EP (Week 28 to 52) and during the maintenance period (MP; Week 28 to end of trial)
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 and at end of treatment
Timeframe: Baseline and up to 3.3 years
Number of blood pressure (BP) exacerbation events per 100 patient years
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Number of participants with least one BP exacerbation event during study
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Percentage of participants with least one BP exacerbation event during study
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Time to stopping randomized treatment due to meeting rescue criteria
Timeframe: Randomization (Day 1) to end of study (event-driven, up to 3.3 years)
Mean change in SF-36 Health Related Quality of Life (HRQOL) scores between Baseline and Weeks 8, 12, 28, 52, of particular interest are the changes from Baseline in the vitality and physical functioning domains at Weeks 28 and 52
Timeframe: Baseline, and up to and including Week 52
Change from Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) score at Week 52
Timeframe: Baseline, and up to and including Week 52
Change from Baseline in EQ-5D-5L visual analog scale (VAS) at Week 52
Timeframe: Baseline, and up to and including Week 52
Change from Baseline in Patient Global Impression of Severity Scale (PGI-S) at Week 8, 12, 28 and 52
Timeframe: Baseline, and up to and including Week 52
Interventions:
Enrollment:
2964
Primary completion date:
2020-09-11
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Ajay K. Singh, Kevin Carroll, Vlado Perkovic, Scott Solomon, Vivekanand Jha, Kirsten, L. Johansen, Renato D. Lopes, Iain C. Macdougall, Gregorio T. Obrador, Sushrut S. Waikar, Christoph Wanner, David C. Wheeler, Andrzej Wiecek, Allison Blackorby, Borut Cizman, Alexander R. Cobitz, Rich Davies, Jo Dole, Lata Kler, Amy M. Meadowcroft, Xinyi Zhu, John J. V. McMurray for the ASCEND-D study group. DAPRODUSTAT FOR THE TREATMENT OF ANEMIA IN PATIENTS UNDERGOING DIALYSIS. N Engl J Med. 2021;
DOI: 10.1056/NEJMoa2113379
PMID: 34739194
Medical condition
Anaemia, Aspergillosis, Allergic Bronchopulmonary
Product
GSK584430, SB598954, daprodustat, darbepoetin alfa
Collaborators
Not applicable
Study date(s)
September 2016 to November 2020
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 99 years
Accepts healthy volunteers
No
- Age: 18 to 99 years of age (inclusive).
- Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6 weeks prior to screening and between screening and randomization.
- Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
- Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
Inclusion and exclusion criteria
Inclusion criteria:
- Age: 18 to 99 years of age (inclusive).
- Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6 weeks prior to screening and between screening and randomization.
- Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). On randomization (Day 1): Hgb 8 to 11 g/dL and receiving at least the minimum ESA dose. Hgb >11 g/dL to 11.5 g/dL and receiving greater than the minimum ESA dose.
- Dialysis: On dialysis >90 days prior to screening and continuing on the same mode of dialysis from screening (Week -8) through to randomization (Day 1).
- Frequency of Dialysis: Hemodialysis (HD) >=2 times/week and peritoneal dialysis (PD) >=5 times/week. Home hemodialysis >=2 times/week.
- Compliance with placebo [randomization (Day 1) only]: >=80% and <=120% compliance with placebo during run-in period.
- Informed consent (screening only): capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Exclusion criteria:
- Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
- Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
- Transferrin saturation (TSAT) (screening only): <=20%.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia.
- Other causes of anemia: Untreated Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.
- Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=4 weeks prior to screening through to randomization (Day 1).
- MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).
- Stroke or transient ischemic attack: <=4 weeks prior to screening through to randomization (Day 1).
- Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
- Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator that would contraindicate the use of recombinant human erythropoietin (rhEPO).
- Bazett’s corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QT Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.
- Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.
- Bilirubin: >1.5xULN at screening.
- Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1) or currently receiving treatment for cancer, or complex kidney cyst (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=4 weeks prior to screening.
- Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or epoetin alfa or darbepoetin alfa.
- Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
- Other study participation: Use of other investigational agent or device prior to screening through to randomization (Day 1).
- Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of >30 days.
- Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy.
- Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g., intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Trial location(s)
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Location
GSK Investigational Site
Aguascalientes, Aguascalientes, Mexico, 20230
Status
Study Complete
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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
Study complete
Actual primary completion date
2020-09-11
Actual study completion date
2020-09-11
Plain language summaries
Summary of results in plain language
Available language(s): English, Afrikaans, German (Austria), Bulgarian, Catalan, Czech, Danish, Dutch (Belgium), Dutch, Estonian, French (Belgium), French (Canadian), French, German, Greek, Gujarati, Hindi, Hungarian, Italian, Kannada, Korean, Malay (Malaysia), Malayalam, Marathi, Norwegian, Polish, Portuguese (Brazil), Portuguese (Native), Romanian, Russian, Samoan, Chinese (Simplified), Spanish (Argentina), Spanish (Mexico), Spanish, Spanish (United States), Swedish, Tamil (India), Tamil (Malaysia), Tamil (Singapore), Telugu, Chinese (Taiwan), Turkish, Ukrainian, Urdu, Xhosa, Tongan (New Zealand)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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