Phase 2 Open-Label Study to Assess the Efficacy, Safety, and Tolerability of AKB-6548 in Subjects With Anemia Secondary to End Stage Renal Disease (ESRD), Undergoing Chronic Hemodialysis.
Overview
- Phase
- Phase 2
- Intervention
- AKB-6548
- Conditions
- Anemia
- Sponsor
- Akebia Therapeutics
- Enrollment
- 94
- Primary Endpoint
- Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with end stage renal disease undergoing chronic hemodialysis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 to 79 years inclusive
- •Chronic Kidney Disease (CKD) Stage 5 on chronic hemodialysis for at least 3 months
- •Anemia secondary to CKD treated with erythropoiesis stimulating agent and intravenous iron
Exclusion Criteria
- •Body mass index \>44.0 kilograms per meter squared (kg/m\^2)
- •Transfusion within 8 weeks prior to Screening
- •Alanine transaminase or total bilirubin \>1.25x ULN
- •Uncontrolled hypertension
- •Class III or IV congestive heart failure
- •Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack within 6 months prior to Screening
Arms & Interventions
AKB-6548, starting dose 1
Intervention: AKB-6548
AKB-6548, starting dose 2
Intervention: AKB-6548
AKB-6548, starting dose 3
Intervention: AKB-6548
Outcomes
Primary Outcomes
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
Time Frame: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8
Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.
Change From Pre-dose Average in Hgb Level to The End-of-study Average
Time Frame: Pre-dose, Week 15, and Week 16
Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Change From Mid-study Average in Hgb Level to The End-of-study Average
Time Frame: Week 7, Week 8, Week 15, and Week 16
Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Secondary Outcomes
- Change From Baseline in Absolute Reticulocyte Count(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Transferrin Saturation (TSAT)(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite(Pre-dialysis and post-dialysis on Week 2 and Week 16)
- Change From Baseline in Hematocrit(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Red Blood Cell (RBC) Count(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Percent Reticulocyte Count(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Ferritin(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Hepcidin(Baseline, Week 8, and Week 16)
- Change From Baseline in Total Iron-Binding Capacity (TIBC)(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Iron(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Reticulocyte Hgb Content(Baseline, Week 2, Week 4, Week 8, and Week 16)
- Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy(Up to Week 16)
- Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings(Up to Week 20)
- Change From Baseline in Hgb(Baseline, Week 4, Week 8, Week 12, and Week 16)
- Number of Participants Who Received Blood Transfusion Rescue Therapy(Up to Week 16)
- Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite(Pre-dialysis and post-dialysis on Week 2 and Week 16)
- Number of Participants With Clinically Significant Changes From Baseline in Vital Signs(Up to Week 20)
- Mean Plasma Concentrations of Vadadustat(Pre-dialysis and post-dialysis on Week 2 and Week 16)
- Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to Week 20)
- Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values(Up to Week 20)