Back to resultsDose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
Primary Purpose
Anemia, Non-dialysis Dependent Chronic Kidney Disease
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Vadadustat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Anemia focused on measuring Anemia, kidney, non-dialysis dependent chronic kidney disease, CKD, NDD-CKD, renal, vadadustat, AKB-6548, hypoxia-inducible factor, hypoxia-inducible factor (HIF), HIF, prolyl-hydroxylase inhibitor (PHI), PHI, Japan, Japanese, Akebia (AKB)
Eligibility Criteria
Inclusion Criteria:
- Male and female Japanese participants ≥20 years of age
- Diagnosis of chronic kidney disease (CKD) based on an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m^2)
- Hemoglobin (Hb) ≤10.5 grams per deciliter (g/dL)
- Not currently being treated with dialysis and not expected to start dialysis within 3 months of 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
- Intravenous iron within 4 weeks prior to or during screening
- Any use of erythropoiesis-stimulating agents within 6 weeks prior to or during screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Vadadustat, Dose 1
Vadadustat, Dose 2
Vadadustat, Dose 3
Placebo
Arm Description
Daily oral dose
Daily oral dose
Daily oral dose
Daily oral dose
Outcomes
Primary Outcome Measures
Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
The pre-treatment value for Hb was defined as the average of 2 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 Outcome Measures
Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL 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.
Mean Hb Levels at the End of the Primary Efficacy Period
Data are reported as mean of the actual Week 6 values.
Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
Data are reported as mean of the actual Week 16 values.
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
Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
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.
Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
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.
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
Increases in dose were not allowed during the 6-week Primary Efficacy Period.
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
Blood samples were collected for analysis.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
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.
Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03054337
Brief Title
Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
Official 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 Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
October 2016 (Actual)
Primary Completion Date
July 4, 2017 (Actual)
Study Completion Date
August 28, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akebia Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
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 Non-dialysis Dependent Chronic Kidney Disease (NDD-CKD).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Non-dialysis Dependent Chronic Kidney Disease
Keywords
Anemia, kidney, non-dialysis dependent chronic kidney disease, CKD, NDD-CKD, renal, vadadustat, AKB-6548, hypoxia-inducible factor, hypoxia-inducible factor (HIF), HIF, prolyl-hydroxylase inhibitor (PHI), PHI, Japan, Japanese, Akebia (AKB)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vadadustat, Dose 1
Arm Type
Experimental
Arm Description
Daily oral dose
Arm Title
Vadadustat, Dose 2
Arm Type
Experimental
Arm Description
Daily oral dose
Arm Title
Vadadustat, Dose 3
Arm Type
Experimental
Arm Description
Daily oral dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Daily oral dose
Intervention Type
Drug
Intervention Name(s)
Vadadustat
Other Intervention Name(s)
AKB-6548
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
Description
The pre-treatment value for Hb was defined as the average of 2 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.
Time Frame
Pre-treatment; Week 6
Secondary Outcome Measure Information:
Title
Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16
Description
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.
Time Frame
from Baseline up to Week 16
Title
Mean Hb Levels at the End of the Primary Efficacy Period
Description
Data are reported as mean of the actual Week 6 values.
Time Frame
up to Week 6
Title
Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
Description
Data are reported as mean of the actual Week 16 values.
Time Frame
up to Week 16
Title
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
Title
Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
Description
The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
Time Frame
Pre-treatment; Week 16
Title
Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 6
Title
Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 16
Title
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 6
Title
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 16
Title
Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 6
Title
Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 16
Title
Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 6
Title
Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 16
Title
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 6
Title
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Week 16
Title
Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
Description
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.
Time Frame
Baseline; Week 6
Title
Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
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.
Time Frame
Baseline; Week 16
Title
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
Description
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time Frame
Baseline; Week 6
Title
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time Frame
Baseline; Week 16
Title
Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
Description
Increases in dose were not allowed during the 6-week Primary Efficacy Period.
Time Frame
Baseline to Week 16
Title
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6
Description
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time Frame
Baseline to Week 6
Title
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16
Description
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time Frame
Baseline to Week 16
Title
Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
Description
Blood samples were collected for analysis.
Time Frame
Week 4, pre-dose
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
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. 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.
Time Frame
up to Week 6
Title
Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
Description
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.
Time Frame
up to Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female Japanese participants ≥20 years of age
Diagnosis of chronic kidney disease (CKD) based on an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m^2)
Hemoglobin (Hb) ≤10.5 grams per deciliter (g/dL)
Not currently being treated with dialysis and not expected to start dialysis within 3 months of 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
Intravenous iron within 4 weeks prior to or during screening
Any use of erythropoiesis-stimulating agents within 6 weeks prior to or during screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Akebia Therapeutics
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
City
Aichi
Country
Japan
City
Chiba
Country
Japan
City
Ehime
Country
Japan
City
Gunma
Country
Japan
City
Hiroshima
Country
Japan
City
Hokkaido
Country
Japan
City
Hyogo
Country
Japan
City
Ibaraki
Country
Japan
City
Kanagawa
Country
Japan
City
Nagano
Country
Japan
City
Nara
Country
Japan
City
Niigata
Country
Japan
City
Oita
Country
Japan
City
Okayama
Country
Japan
City
Okinawa
Country
Japan
City
Osaka
Country
Japan
City
Shiga
Country
Japan
City
Tokushima
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
36005278
Citation
Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
Results Reference
derived
Learn more about this trial
Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)
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