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

Akebia Therapeutics94 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Anemia End Stage Renal Disease

Interventions

AKB-6548DRUG

Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

AKB-6548DRUG

Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

AKB-6548DRUG

Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 Years

Medical Language ↔ Plain English

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

Locations (16)

Unnamed facility

El Granada, California, United States

Unnamed facility

Long Beach, California, United States

Unnamed facility

San Dimas, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Week 7, Week 8, Week 15, and Week 16

Secondary Outcomes

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.

Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16

Change From Baseline in Hematocrit

Data from ClinicalTrials.gov

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Unnamed facility

Santa Clarita, California, United States

Unnamed facility

Whittier, California, United States

Unnamed facility

Arvada, Colorado, United States

Unnamed facility

Westminster, Colorado, United States

Unnamed facility

Naples, Florida, United States

Unnamed facility

North Miami Beach, Florida, United States

Unnamed facility

Augusta, Georgia, United States

...and 6 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to Week 20