Clinical trial NCT03054350: Dose-Finding Study of Vadadustat in Japanese Subjects With Anemia Secondary to Dialysis-Dependent Chronic Kidney Disease (DD-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 Dialysis-Dependent Chronic Kidney Disease (DD-CKD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Dialysis Dependent Chronic Kidney Disease
Keywords: Anemia
kidney
dialysis dependent chronic kidney disease
CKD
DD
renal
vadadustat
AKB-6548
hypoxia-inducible factor
Akebia (AKB)
hypoxia-inducible factor (HIF)
HIF
prolyl-hydroxylase inhibitor (PHI)
PHI
Japan
Japanese
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-02-15
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 Dialysis-dependent Chronic Kidney Disease (DD-CKD).


Eligibility criteria: 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

Primary outcomes:
measure: Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
timeFrame: Pre-treatment; Week 6
Secondary outcomes:
measure: Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16
timeFrame: from Baseline up to Week 16
measure: Mean Hb Levels at the End of the Primary Efficacy Period
timeFrame: up to Week 6
measure: Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
timeFrame: up to Week 16
measure: 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
timeFrame: up to Week 16
measure: Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
timeFrame: Pre-treatment; Week 16
measure: Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Number of Participants Who Required Rescue With RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Number of Participants Who Required Rescue With Erythropoiesis-Stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
timeFrame: Baseline; Week 6
measure: Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: Baseline; Week 16
measure: Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
timeFrame: up to Week 16
measure: Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
timeFrame: Week 4, pre-dose
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
timeFrame: up to Week 6
measure: Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
timeFrame: up to Week 16
Other outcomes:
Locations:
city: Aichi
country: Japan
city: Ehime
country: Japan
city: Fukui
country: Japan
city: Hiroshima
country: Japan
city: Hokkaido
country: Japan
city: Hyogo
country: Japan
city: Ibaraki
country: Japan
city: Kagoshima
country: Japan
city: Kochi
country: Japan
city: Miyagi
country: Japan
city: Nagano
country: Japan
city: Nagasaki
country: Japan
city: Niigata
country: Japan
city: Oita
country: Japan
city: Okinawa
country: Japan
city: Osaka
country: Japan
city: Saitama
country: Japan
city: Shizuoka
country: Japan
Study officials:
affiliation: Sponsor GmbH
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References:
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.