Last updated: 07/17/2024 17:09:09
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-in Incident Dialysis (ASCEND-ID)
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A 52-week open-label (sponsor-blind), randomized, active-controlled, parallel-group, multi-center study to evaluate the efficacy and safety of daprodustat compared to recombinant human erythropoietin in subjects with anemia associated with chronic kidney disease who are initiating dialysis
Trial description: The purpose of this multi-center study is to evaluate the efficacy and safety of daprodustat in subjects with anemia associated with CKD.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline in hemoglobin (Hgb) during evaluation period (EP)
Timeframe: Randomization (Day 1) to Week 52
Secondary outcomes:
Average monthly IV iron dose milligrams (mg) per subject from Baseline to Week 52
Timeframe: Randomization (Day 1) to Week 52
Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
Timeframe: Randomization (Day 1) to Week 52
Number of BP exacerbation events per 100 patient years
Timeframe: Up to Week 58
Number (%) of subjects with at least one BP exacerbation event during study
Timeframe: Up to Week 58
Change from Baseline in Hgb up to Week 52
Timeframe: Baseline and up to Week 52
Number (%) of Hgb responders
Timeframe: Week 28 to Week 52
Percentage time for which Hgb is in analysis range during the EP
Timeframe: Week 28 to Week 52
Time to rescue
Timeframe: Up to Week 52
Change in short form (SF)-36 health-related quality of life (HRQOL) scores
Timeframe: Baseline and up to Week 52
Change from Baseline in Health Utility EuroQol five dimensions five level (EQ-5D-5L) questionnaire score at Week 52
Timeframe: Baseline and Week 52
Change from Baseline in EQ visual analogue scale (VAS) at Week 52
Timeframe: Baseline and Week 52
Change from Baseline in the CKD- Anemia Symptoms Questionnaire (AQ)
Timeframe: Baseline and Week 52
Change from Baseline in patient global impression of severity (PGI-S)
Timeframe: Baseline and up to Week 52
Summary of pharmacokinetic parameters of plasma daprodustat and three major metabolites in dialysis subjects
Timeframe: Predose, 0.5, 1, 2, and 3 hours post dose at Week 4, 8 or 12
Interventions:
Enrollment:
313
Primary completion date:
2020-24-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Ajay K. Singh, Borut Cizman, Kevin Carroll, John J. V. McMurray, Vlado Perkovic, Vivekanand Jha, Kirsten, L. Johansen, Renato D. Lopes, Iain C. Macdougall, Gregorio T. Obrador, Sushrut S. Waikar, Christoph Wanner, David C. Wheeler, Andrzej Wiecek, Nicole Stankus, Frank Strutz, Allison Blackorby, Alexander R. Cobitz, Amy M. Meadowcroft, Gitanjali Paul, Prerna Ranganathan, Sangeeta Sedani, Scott Solomon. Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients. JAMA Intern Med. 2022;
DOI:10.1001/jamainternmed.2022.0605
PMID: NULL
Medical condition
Anaemia
Product
daprodustat, darbepoetin alfa
Collaborators
Not applicable
Study date(s)
May 2017 to September 2020
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 99 years
Accepts healthy volunteers
No
- 18 to 99 years of age inclusive.
- Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of <=90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD >=2 times per week or PD >=4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
- Planned living-related or living-unrelated kidney transplant during the study.
- Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L]) at screening or after IV iron supplementation.
Inclusion and exclusion criteria
Inclusion criteria:
- 18 to 99 years of age inclusive.
- Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of <=90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD >=2 times per week or PD >=4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
- Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL (5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L) at randomization.
- 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:
- Planned living-related or living-unrelated kidney transplant during the study.
- Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L]) at screening or after IV iron supplementation.
- Transferrin saturation (TSAT): <=20% at screening or after IV iron supplementation.
- Vitamin B12 (cobalamin): Below the lower limit of the reference range at screening or after vitamin B12 supplementation.
- Folate: <2.0 ng/mL (<4.5 nanomoles per liter [nmol/L]) at screening.
- Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).
- 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 <=10 weeks prior to screening through to randomization (Day 1).
- Use of any Erythropoiesis-stimulating agent (ESA) treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation. Note : Limited use is defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of 20000 unit total) or long acting ESA (darbepoetin alfa [maximum of 100 mcg total] or methoxy polyethylene glycol-epoetin beta [maximum of 125 mcg total]) received before or after starting dialysis.
- Myocardial infarction or acute coronary syndrome: <=10 weeks prior to screening through to randomization (Day 1).
- Stroke or transient ischemic attack: <=10 weeks prior to screening through to randomization (Day 1).
- Chronic Class IV heart failure, 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.
- QT correction using Bazett's (QTcB) (Day 1): QTcB >500 milliseconds (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects with a predominantly ventricular paced rhythm.
- Liver disease (any one of the following): 1. Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only). 2. Bilirubin >1.5 times ULN (screening only) (NOTE: Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 3. 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. NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic hepatitis B or C, or Gilbert’s syndrome) are acceptable if subject otherwise meets entry criteria.
- 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 (i.e. Bosniak Category II F, III or IV) >3 centimeter (cm). The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=10 weeks prior to screening.
- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product or to darbepoetin alfa.
- Use of strong Cytochrome P4502C8 (CYP2C8) inhibitors (example gemfibrozil) or strong CYP2C8 inducers (example rifampin/rifampicin).
- Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half-lives (whichever is longer).
- Any prior treatment with daprodustat for treatment duration of >30 days.
- Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotropin (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 in the List of Highly Effective Methods for Avoiding Pregnancy.
- 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 (example 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
Anaheim, California, United States, 92801
Status
Study Complete
Location
GSK Investigational Site
Anyang-Si, Gyeonggi-do, South Korea, 14068
Status
Study Complete
Location
GSK Investigational Site
Augusta, Georgia, United States, 30912
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21287
Status
Study Complete
Showing 1 - 6 of 110 Results
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
2020-24-09
Actual study completion date
2020-24-09
Plain language summaries
Summary of results in plain language
Available language(s): English, Spanish (Argentina), French (Canadian), German, Hindi, Kannada, Marathi, Malayalam, Tamil (India), Telugu, Gujarati, Urdu, Italian, Korean, Chinese (Malaysia), Malay (Malaysia), Tamil (Malaysia), Spanish (Mexico), Polish, Russian, Spanish, Catalan
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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