16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis

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.

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.

Study Overview

• Status: Completed
• Conditions: Anemia; End Stage Renal Disease
• Intervention / Treatment: Drug: AKB-6548; Drug: AKB-6548; Drug: AKB-6548

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • El Granada, California, United States
    • Long Beach, California, United States
    • San Dimas, California, United States
    • Santa Clarita, California, United States
    • Whittier, California, United States
  • Colorado
    • Arvada, Colorado, United States
    • Westminster, Colorado, United States
  • Florida
    • Naples, Florida, United States
    • North Miami Beach, Florida, United States
  • Georgia
    • Augusta, Georgia, United States
  • New York
    • Astoria, New York, United States
  • Texas
    • Arlington, Texas, United States
    • Grand Prairie, Texas, United States
    • Greenville, Texas, United States
    • Houston, Texas, United States
  • Virginia
    • Mechanicsville, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AKB-6548, starting dose 1	Drug: AKB-6548; Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.
Experimental: AKB-6548, starting dose 2	Drug: AKB-6548; Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.
Experimental: AKB-6548, starting dose 3	Drug: AKB-6548; Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.; Drug: AKB-6548; Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average	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.	Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8
Change From Pre-dose Average in Hgb Level to The End-of-study Average	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.	Pre-dose, Week 15, and Week 16
Change From Mid-study Average in Hgb Level to The End-of-study Average	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.	Week 7, Week 8, Week 15, and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hgb	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hematocrit	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Red Blood Cell (RBC) Count	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Absolute Reticulocyte Count	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Percent Reticulocyte Count	Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Reticulocyte Hgb Content	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing.	Baseline, Week 2, Week 4, Week 8, and Week 16
Change From Baseline in Ferritin	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Hepcidin	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication.	Baseline, Week 8, and Week 16
Change From Baseline in Total Iron-Binding Capacity (TIBC)	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Transferrin Saturation (TSAT)	Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Change From Baseline in Iron	Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication.	Baseline, Week 4, Week 8, Week 12, and Week 16
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy	ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.	Up to Week 16
Number of Participants Who Received Blood Transfusion Rescue Therapy	Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.	Up to Week 16
Mean Plasma Concentrations of Vadadustat	Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.	Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite	Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.	Pre-dialysis and post-dialysis on Week 2 and Week 16
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite	Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.	Pre-dialysis and post-dialysis on Week 2 and Week 16
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.	Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes.	Up to Week 20
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes.	Up to Week 20
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings	A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator.	Up to Week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Intravenous Iron Replacement Therapy	Intravenous iron was administered throughout the study to maintain ferritin levels in the range of ≥100 ng/mL to ≤1200 ng/mL.	Baseline, Week 8, and Week 16

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Publications and helpful links

Helpful Links

• Vadadustat, a Novel, Oral Treatment for Anemia of CKD, Maintains Stable Hemoglobin Levels in Dialysis Patients Converting from Erythropoiesis-Stimulating Agents

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2014
• Primary Completion (Actual): July 22, 2015
• Study Completion (Actual): July 22, 2015

Study Registration Dates

• First Submitted: September 25, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 9, 2014

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: hemoglobin; pharmacokinetics; anemia; chronic kidney disease; dialysis; CKD; erythropoietin; renal impairment; kidney; chronic renal insufficiency; end stage renal disease; HIF; oral anemia treatment; hypoxia-inducible factor; HIF-PHI; hypoxia-inducible factor propyl-hydroxylase inhibitor
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Anemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glycine Agents; Glycine
• Other Study ID Numbers: AKB-6548-CI-0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No