Last updated: 07/17/2024 17:26:18
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis subjects evaluating Hemoglobin (Hgb) and Quality of life (ASCEND-NHQ)
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A 28-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, study in recombinant human erythropoietin (rhEPO) naïve non-dialysis participants with anemia associated with chronic kidney disease to evaluate the efficacy, safety and effects on quality of life of daprodustat compared to placebo
Trial description: The purpose of this multi-center study in non-dialysis participants with anemia associated with CKD is to evaluate safety, efficacy and quality of life of daprodustat compared to placebo.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline in Hgb up to evaluation period (EP)
Timeframe: Baseline and up to Week 28
Secondary outcomes:
Percentage of participants with Hgb increase of >=1.0 grams per deciliter (g/dL) from Baseline
Timeframe: Baseline and up to Week 28
Mean change from Baseline in short form-36 (SF-36) questionnaire vitality domain score
Timeframe: Baseline and Week 28
Percentage of Hgb responders
Timeframe: Baseline and up to Week 28
Percentage time Hgb in range
Timeframe: Up to Week 28
Mean change from Baseline for additional Hgb parameters
Timeframe: Baseline and up to Week 28
Time to rescue
Timeframe: Up to Week 28
Mean change from Baseline in CKD - Anemia Questionnaire (CKD-AQ) score
Timeframe: Up to Week 28
Change from Baseline in Patient Global Impression of Severity (PGI-S) score
Timeframe: Baseline and up to Week 28
Mean change from Baseline in SF-36 questionnaire vitality domain score
Timeframe: Baseline and up to Week 28
Mean change from Baseline in SF-36 questionnaire physical function domain score
Timeframe: Baseline and up to Week 28
Percentage of participants currently employed on the work productivity and activity impairment, anemia symptoms, clinical practice version (WPAI-ANS-CPV) scale
Timeframe: Up to Week 28
Change from Baseline in percent mean hours work time missed on the WPAI-ANS
Timeframe: Baseline and up to Week 28
CPV change from Baseline in percent impaired on the WPAI-ANS-CPV questionnaire
Timeframe: Baseline and up to Week 28
Change from Baseline in overall percent work impairment on the WPAI-ANS-CPV questionnaire
Timeframe: Baseline and up to Week 28
Change from Baseline in percent activity impairment on the WPAI-ANS-CPV questionnaire
Timeframe: Baseline and at Week 28
Change from Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) score
Timeframe: Baseline and up to Week 28
Change from Baseline EuroQol Visual Analogue Scale (EQ-VAS) score
Timeframe: Baseline and up to Week 28
Change from Baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) at Week 28
Timeframe: Baseline and at Week 28
Percentage of participants with at least one BP exacerbation
Timeframe: Up to Week 28
Interventions:
Enrollment:
614
Primary completion date:
2020-07-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kirsten Johansen, Alexander R. Cobitz, Ajay K. Singh, Iain C. Macdougall, Renato D. Lopes, Gregorio T. Obrador, Csaba P. Kovesdy, Rubeen Israni, Purav Bhatt, Aliistair Lindsay, ivekanand Jha, Tony Okoro, Mike Sprys, Shivinder Jolly, Rodrigo Refoios Camejo, Tom Keeley, Borut Cizman, David C. Wheeler. Effects of Daprodustat on Haemoglobin and Quality of Life in Non-Dialysis CKD Patients: Results of the ASCEND-NHQ Randomised, Double-blind, Placebo-controlled Trial. Kidney Int. 2023;
DOI: 10.1016/j.kint.2023.02.019
PMID: NULL
Medical condition
Anaemia
Product
daprodustat
Collaborators
Not applicable
Study date(s)
March 2018 to October 2020
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- >=18 years of age at the time of signing the informed consent.
- Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
- Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
Inclusion and exclusion criteria
Inclusion criteria:
- >=18 years of age at the time of signing the informed consent.
- Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
- Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
- If needed, participant may be on stable maintenance oral iron supplementation. There should be <50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
- Male and female participants are eligible. A female participant 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 WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
- Capable of giving signed informed consent.
Exclusion criteria:
- Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
- Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
- Transferrin saturation (TSAT) <15 percent (Screening only).
- Ferritin <50 nanograms per milliliter (ng/mL) (Screening only).
- History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
- History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
- History of bone marrow aplasia or pure red cell aplasia (PRCA).
- Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
- Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding <= 8 weeks prior to screening through to randomization (Day 1).
- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
- Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
- Ferric citrate use within 4 weeks prior to randomization (Day 1).
- Use of other investigational agent or device prior to screening through to randomization (Day 1).
- Any prior treatment with daprodustat for a treatment duration of >30 days.
- MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
- Stroke or transient ischemic attack within the 8 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.
- QT interval corrected by Bazett's formula (QTcB) >500 milliseconds (msec) or QTcB >530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
- Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening (Week -4).
- Bilirubin >1.5xULN at screening (Week -4).
- 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.
- 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 (for example, Bosniak Category II F, III or IV) > 3 centimeters (cm).
- Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
- Current uncontrolled hypertension as determined by the investigator.
Trial location(s)
Location
GSK Investigational Site
Adairsville, Georgia, United States, 30103
Status
Study Complete
Location
GSK Investigational Site
Asheville, North Carolina, United States, 28801
Status
Study Complete
Location
GSK Investigational Site
Beaver, Pennsylvania, United States, 15009
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
2020-07-10
Actual study completion date
2020-07-10
Plain language summaries
Summary of results in plain language
Available language(s): English, French (Canadian), French, Italian, Korean, Polish, Portuguese (Brazil), Romanian, Russian, Spanish (Argentina), Spanish (Mexico), Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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