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Completed

NCT Number: NCT03054350

Dose-Finding Study 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).

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Key information

Conditions

Anemia Dialysis Dependent Chronic Kidney Disease Hematologic Diseases Hemic and Lymphatic Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aichi, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Vadadustat

Drug

Daily oral dose

Other names: AKB-6548

Placebo

Drug

Daily oral dose

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. Mean Hb Levels at the End of the Primary Efficacy Period

    Time frame: up to Week 6

    Data are reported as mean of the actual Week 6 values.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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.

  17. 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

    Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.

  18. 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.

  19. 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.

  20. 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

    Increases in dose were not allowed during the 6-week Primary Efficacy Period.

  21. 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.

  22. 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

    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.

  23. 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.

Sponsors and collaborators

Lead sponsor

Akebia Therapeutics

Industry

Registry information

Official study title

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)

Important dates

Study start
2016
Primary completion
2017
Study completion
2018
First posted
Feb 15, 2017
Registry last updated
Apr 8, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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