- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03054350
Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
March 15, 2021 updated by: Akebia Therapeutics
Phase 2, Randomized, Double-Blind, Placebo Controlled, Dose-Finding Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Vadadustat in Japanese Subjects With Anemia Secondary to Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
This is a Phase 2, randomized, double-blind, placebo-controlled, dose-finding study to assess the efficacy, safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of orally administered vadadustat in Japanese participants with anemia secondary to Dialysis-dependent Chronic Kidney Disease (DD-CKD).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
60
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Aichi, Japan
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Ehime, Japan
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Fukui, Japan
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Hiroshima, Japan
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Hokkaido, Japan
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Hyogo, Japan
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Ibaraki, Japan
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Kagoshima, Japan
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Kochi, Japan
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Miyagi, Japan
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Nagano, Japan
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Nagasaki, Japan
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Niigata, Japan
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Oita, Japan
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Okinawa, Japan
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Osaka, Japan
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Saitama, Japan
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Shizuoka, Japan
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male and female Japanese participants ≥20 years of age
- Receiving chronic maintenance hemodialysis for end-stage kidney disease
- Hemoglobin (Hb) <10.0 grams per deciliter (g/dL)
Exclusion Criteria:
- Anemia due to a cause other than chronic kidney disease (CKD) or presence of active bleeding or recent blood loss
- Sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia
- Red blood cell transfusion within 4 weeks prior to or during screening
- Anticipated to recover adequate kidney function to no longer require hemodialysis during study participation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vadadustat, Dose 1
Daily oral dose
|
Daily oral dose
Other Names:
|
Experimental: Vadadustat, Dose 2
Daily oral dose
|
Daily oral dose
Other Names:
|
Experimental: Vadadustat, Dose 3
Daily oral dose
|
Daily oral dose
Other Names:
|
Placebo Comparator: Placebo
Daily oral dose
|
Daily oral dose
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
Time Frame: Pre-treatment; Week 6
|
The pre-treatment average value for Hb was defined as the average of 3 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value.
Change from Pre-treatment was calculated as the Week 6 value minus the Pre-treatment value.
|
Pre-treatment; Week 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16
Time Frame: from Baseline up to Week 16
|
Time for this analysis was measured from Day 1 (Baseline) through the point in time during either the Primary Efficacy Period or the Dose Adjustment and Maintenance Period when a participant's Hb level achieved the target range of 10.0 to 12.0 g/dL.
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from Baseline up to Week 16
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Mean Hb Levels at the End of the Primary Efficacy Period
Time Frame: up to Week 6
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Data are reported as mean of the actual Week 6 values.
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up to Week 6
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Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
Time Frame: up to Week 16
|
Data are reported as mean of the actual Week 16 values.
|
up to Week 16
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Number of Participants Who Achieved the Target Hb Level of 10.0 to 12.0 g/dL at the End of the Dose Adjustment and Maintenance Period
Time Frame: up to Week 16
|
up to Week 16
|
|
Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
Time Frame: Pre-treatment; Week 16
|
A pre-treatment average value for Hb was defined as the average of 3 values obtained prior to dosing, i.e., the 2 qualifying screening values and the Baseline value.
Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
|
Pre-treatment; Week 16
|
Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 6
|
Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 16
|
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 6
|
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 16
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Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 6
|
Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 16
|
Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 6
|
Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Baseline; Week 16
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Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 6
|
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
|
Baseline; Week 16
|
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
|
Baseline; Week 6
|
Number of Participants Who Required Rescue With RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
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Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
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Baseline; Week 16
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Number of Participants Who Required Rescue With Erythropoiesis-Stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
Time Frame: Baseline; Week 6
|
ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion.
Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
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Baseline; Week 6
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Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: Baseline; Week 16
|
ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is <9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion.
Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
|
Baseline; Week 16
|
Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
Time Frame: up to Week 16
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Increases in dose were not allowed during the 6-week Primary Efficacy Period.
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up to Week 16
|
Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
Time Frame: Week 4, pre-dose
|
Blood samples were collected for analysis.
|
Week 4, pre-dose
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
Time Frame: up to Week 6
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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.
An AE 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.
An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
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up to Week 6
|
Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
Time Frame: up to Week 16
|
An AE was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period.
An AE 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.
An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
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up to Week 16
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2016
Primary Completion (Actual)
October 24, 2017
Study Completion (Actual)
January 24, 2018
Study Registration Dates
First Submitted
February 13, 2017
First Submitted That Met QC Criteria
February 13, 2017
First Posted (Actual)
February 15, 2017
Study Record Updates
Last Update Posted (Actual)
April 8, 2021
Last Update Submitted That Met QC Criteria
March 15, 2021
Last Verified
March 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AKB-6548-CI-0022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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