Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)

Anemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03054337
• Other study ID #: AKB-6548-CI-0021
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: August 28, 2017

Study information

• Verified date: March 2021
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: August 28, 2017
• Est. primary completion date: July 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Non-dialysis Dependent Chronic Kidney Disease
• Renal Insufficiency, Chronic

Intervention

Drug:
• Vadadustat

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Akebia Therapeutics

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Pre-treatment; Week 6
Secondary	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.	from Baseline up to Week 16
Secondary	Mean Hb Levels at the End of the Primary Efficacy Period	Data are reported as mean of the actual Week 6 values.	up to Week 6
Secondary	Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period	Data are reported as mean of the actual Week 16 values.	up to Week 16
Secondary	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		up to Week 16
Secondary	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.	Pre-treatment; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline; Week 6
Secondary	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.	Baseline; Week 16
Secondary	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.	Baseline to Week 16
Secondary	Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6	Iron sufficiency was defined as ferritin =50 ng/mL and TSAT =20%.	Baseline to Week 6
Secondary	Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16	Iron sufficiency was defined as ferritin =50 ng/mL and TSAT =20%.	Baseline to Week 16
Secondary	Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4	Blood samples were collected for analysis.	Week 4, pre-dose
Secondary	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.	up to Week 6
Secondary	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.	up to Week 16