Back to results16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
Primary Purpose
Anemia, End Stage Renal Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AKB-6548
AKB-6548
AKB-6548
Sponsored by
About this trial
This is an interventional treatment trial for Anemia focused on measuring anemia, end stage renal disease, chronic kidney disease, CKD, dialysis, chronic renal insufficiency, renal impairment, erythropoietin, kidney, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor propyl-hydroxylase inhibitor, HIF-PHI, pharmacokinetics
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
AKB-6548, starting dose 1
AKB-6548, starting dose 2
AKB-6548, starting dose 3
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02260193
Brief Title
16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 10, 2014 (Actual)
Primary Completion Date
July 22, 2015 (Actual)
Study Completion Date
July 22, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akebia Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, End Stage Renal Disease
Keywords
anemia, end stage renal disease, chronic kidney disease, CKD, dialysis, chronic renal insufficiency, renal impairment, erythropoietin, kidney, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor propyl-hydroxylase inhibitor, HIF-PHI, pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AKB-6548, starting dose 1
Arm Type
Experimental
Arm Title
AKB-6548, starting dose 2
Arm Type
Experimental
Arm Title
AKB-6548, starting dose 3
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AKB-6548
Intervention Description
Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Intervention Type
Drug
Intervention Name(s)
AKB-6548
Intervention Description
Starting dose 2. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Intervention Type
Drug
Intervention Name(s)
AKB-6548
Intervention Description
Starting dose 3. Oral dose administered three times weekly for 16 weeks. Dose adjustment based on hemoglobin levels as defined in the protocol.
Primary Outcome Measure Information:
Title
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
Description
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
Title
Change From Pre-dose Average in Hgb Level to The End-of-study Average
Description
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
Title
Change From Mid-study Average in Hgb Level to The End-of-study Average
Description
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 Outcome Measure Information:
Title
Change From Baseline in Hgb
Description
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
Title
Change From Baseline in Hematocrit
Description
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
Title
Change From Baseline in Red Blood Cell (RBC) Count
Description
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
Title
Change From Baseline in Absolute Reticulocyte Count
Description
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
Title
Change From Baseline in Percent Reticulocyte Count
Description
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
Title
Change From Baseline in Reticulocyte Hgb Content
Description
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
Title
Change From Baseline in Ferritin
Description
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
Title
Change From Baseline in Hepcidin
Description
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
Title
Change From Baseline in Total Iron-Binding Capacity (TIBC)
Description
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
Title
Change From Baseline in Transferrin Saturation (TSAT)
Description
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
Title
Change From Baseline in Iron
Description
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
Title
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy
Description
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
Title
Number of Participants Who Received Blood Transfusion Rescue Therapy
Description
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
Title
Mean Plasma Concentrations of Vadadustat
Description
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
Title
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite
Description
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
Title
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite
Description
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
Title
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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
Title
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Description
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
Title
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Description
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
Title
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
Description
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
Other Pre-specified Outcome Measures:
Title
Mean Intravenous Iron Replacement Therapy
Description
Intravenous iron was administered throughout the study to maintain ferritin levels in the range of ≥100 ng/mL to ≤1200 ng/mL.
Time Frame
Baseline, Week 8, and Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
Akebia Therapeutics Inc.
Official's Role
Study Director
Facility Information:
City
El Granada
State/Province
California
Country
United States
City
Long Beach
State/Province
California
Country
United States
City
San Dimas
State/Province
California
Country
United States
City
Santa Clarita
State/Province
California
Country
United States
City
Whittier
State/Province
California
Country
United States
City
Arvada
State/Province
Colorado
Country
United States
City
Westminster
State/Province
Colorado
Country
United States
City
Naples
State/Province
Florida
Country
United States
City
North Miami Beach
State/Province
Florida
Country
United States
City
Augusta
State/Province
Georgia
Country
United States
City
Astoria
State/Province
New York
Country
United States
City
Arlington
State/Province
Texas
Country
United States
City
Grand Prairie
State/Province
Texas
Country
United States
City
Greenville
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Mechanicsville
State/Province
Virginia
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://ir.akebia.com/static-files/0c2473ab-894a-44de-9ee9-22734dca47bf
Description
Vadadustat, a Novel, Oral Treatment for Anemia of CKD, Maintains Stable Hemoglobin Levels in Dialysis Patients Converting from Erythropoiesis-Stimulating Agents
Learn more about this trial
16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
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