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)

• Status: Completed
• Trial end date: 2020-10-07
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Epoetin Alfa; Prolyl-Hydroxylase Inhibitors

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.