Study to Evaluate Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Who Are Hyporesponsive to Erythropoiesis Stimulating Agents

Sponsor
Akebia Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT03140722
Collaborator
(none)
2
18
2
10.6
0.1
0

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, open-label study to evaluate vadadustat versus epoetin alfa for the treatment of anemia in subjects with Dialysis-dependent Chronic Kidney Disease (DD-CKD) who are hyporesponsive to erythropoiesis stimulating agents (ESAs.)

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Treatment of Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Who Are Hyporesponsive to Erythropoiesis Stimulating Agents
Actual Study Start Date :
May 2, 2017
Actual Primary Completion Date :
Mar 21, 2018
Actual Study Completion Date :
Mar 21, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: vadadustat

Vadadustat daily oral dose, adjustable based on Hb level

Drug: vadadustat
vadadustat
Other Names:
  • AKB-6548
  • Active Comparator: epoetin alfa

    Epoetin alfa, dose adjustable based on Hb level, as clinically indicated throughout the study

    Drug: epoetin alfa
    epoetin alfa

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period [Baseline; up to 20 weeks]

    Secondary Outcome Measures

    1. Number of Participants Demonstrating Incremental Increases in Hb From Baseline Over Time During the Treatment Period [Baseline; up to 20 weeks]

    2. Number of Participants With Hb Values Within the Target Range of 10.0-11.0 Grams Per Deciliter (g/dL) During the Treatment Period [Baseline; up to 20 weeks]

    3. Number of Participants Receiving Epoetin Alfa Rescue [up to 20 weeks]

    4. Number of Participants Receiving Red Blood Cell Transfusion [up to 20 weeks]

    5. Number of Participants With Specified Levels of Various Biomarkers, Including C-reactive Protein, Hepcidin, and Vascular Endothelial Growth Factor [up to 20 weeks]

    6. Mean Weekly Dose of Intravenous Elemental Iron Administered [up to 20 weeks]

    7. Number of Participants Maintaining Iron Sufficiency (Defined as Ferritin ≥100 Nanograms Per Milliliter and Transferrin Saturation ≥20%) [up to 20 weeks]

    8. Number of Participants Utilizing Resources [up to 20 weeks]

    9. Number of Participants With Treatment-emergent Adverse Events [up to 24 weeks]

      Treatment-emergent adverse events were collected in all participants enrolled in the study.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male and female subjects ≥18 years of age

    • Receiving chronic maintenance hemodialysis for end-stage kidney disease

    • Currently receiving epoetin alfa for anemia

    • Hb between 8.5 and 10.0 g/dL during screening

    Exclusion Criteria:
    • Anemia due to a cause other than 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Bakersfield California United States 93309
    2 Research Site Elk Grove California United States 95758
    3 Research Site Encino California United States 91316
    4 Research Site Escondido California United States 92025
    5 Research Site Lynwood California United States 90262
    6 Research Site San Diego California United States 92115
    7 Research Site San Luis Obispo California United States 93401
    8 Research Site Waterbury Connecticut United States 06708
    9 Research Site Miami Florida United States 33183
    10 Research Site Orlando Florida United States 32804
    11 Research Site Statesboro Georgia United States 30458
    12 Research Site Detroit Michigan United States 48224
    13 Research Site Bronx New York United States 10473
    14 Research Site Philadelphia Pennsylvania United States 19106
    15 Research Site El Paso Texas United States 79915
    16 Research Site Houston Texas United States 77070
    17 Research Site Newport News Virginia United States 23605
    18 Research Site Norfolk Virginia United States 23502

    Sponsors and Collaborators

    • Akebia Therapeutics

    Investigators

    • Study Director: Akebia Therapeutics, Sponsor GmbH

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03140722
    Other Study ID Numbers:
    • AKB-6548-CI-0018
    First Posted:
    May 4, 2017
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Akebia Therapeutics
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Period Title: Overall Study
    STARTED 0 2
    COMPLETED 0 2
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Vadadustat Epoetin Alfa Total
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study. Total of all reporting groups
    Overall Participants 0 2 2
    Age (Count of Participants)
    <=18 years
    0
    NaN
    0
    0%
    Between 18 and 65 years
    1
    Infinity
    1
    50%
    >=65 years
    1
    Infinity
    1
    50%
    Sex: Female, Male (Count of Participants)
    Female
    NA
    NaN
    NA
    NaN
    Male
    NA
    NaN
    NA
    NaN
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    NA
    NaN
    NA
    NaN
    Asian
    NA
    NaN
    NA
    NaN
    Native Hawaiian or Other Pacific Islander
    NA
    NaN
    NA
    NaN
    Black or African American
    NA
    NaN
    NA
    NaN
    White
    NA
    NaN
    NA
    NaN
    More than one race
    NA
    NaN
    NA
    NaN
    Unknown or Not Reported
    NA
    NaN
    NA
    NaN

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period
    Description
    Time Frame Baseline; up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    2. Secondary Outcome
    Title Number of Participants Demonstrating Incremental Increases in Hb From Baseline Over Time During the Treatment Period
    Description
    Time Frame Baseline; up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    3. Secondary Outcome
    Title Number of Participants With Hb Values Within the Target Range of 10.0-11.0 Grams Per Deciliter (g/dL) During the Treatment Period
    Description
    Time Frame Baseline; up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    4. Secondary Outcome
    Title Number of Participants Receiving Epoetin Alfa Rescue
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    5. Secondary Outcome
    Title Number of Participants Receiving Red Blood Cell Transfusion
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    6. Secondary Outcome
    Title Number of Participants With Specified Levels of Various Biomarkers, Including C-reactive Protein, Hepcidin, and Vascular Endothelial Growth Factor
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    7. Secondary Outcome
    Title Mean Weekly Dose of Intravenous Elemental Iron Administered
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    8. Secondary Outcome
    Title Number of Participants Maintaining Iron Sufficiency (Defined as Ferritin ≥100 Nanograms Per Milliliter and Transferrin Saturation ≥20%)
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    9. Secondary Outcome
    Title Number of Participants Utilizing Resources
    Description
    Time Frame up to 20 weeks

    Outcome Measure Data

    Analysis Population Description
    No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 0
    10. Secondary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events
    Description Treatment-emergent adverse events were collected in all participants enrolled in the study.
    Time Frame up to 24 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    Measure Participants 0 2
    Count of Participants [Participants]
    0
    NaN
    0
    0%

    Adverse Events

    Time Frame up to Week 24
    Adverse Event Reporting Description No participants were enrolled in the vadadustat arm of the study.
    Arm/Group Title Vadadustat Epoetin Alfa
    Arm/Group Description Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study.
    All Cause Mortality
    Vadadustat Epoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/2 (0%)
    Serious Adverse Events
    Vadadustat Epoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/2 (0%)
    Other (Not Including Serious) Adverse Events
    Vadadustat Epoetin Alfa
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/2 (0%)

    Limitations/Caveats

    The Study was closed by the Sponsor as it was determined that it was more appropriate to initiate a new study that would explore the broader population utilizing a modified dosing approach (rather than amending the current protocol design).

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Akebia Therapeutics
    Organization Akebia Therapeutics
    Phone (617) 844-6128
    Email trials@akebia.com
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03140722
    Other Study ID Numbers:
    • AKB-6548-CI-0018
    First Posted:
    May 4, 2017
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021