Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction of Anemia in Subjects With Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) (PRO2TECT-CORRECTION)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Akebia Therapeutics
- Enrollment
- 1,751
- Locations
- 4
- Primary Endpoint
- Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
Study Overview
Brief Summary
A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction of anemia and maintenance of hemoglobin (Hb) in participants with Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)
Detailed Description
This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of vadadustat versus Darbepoetin alfa for the correction of anemia and maintenance of Hb in participants with NDD-CKD
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
Sponsor was blinded during the study
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •≥18 years of age
- •Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) at Screening and not expected to start dialysis within 6 months of Screening
- •Mean Screening hemoglobin <10.0 grams per deciliter (g/dL)
- •Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
Exclusion Criteria
- •Anemia due to a cause other than CKD or participants with active bleeding or recent blood loss
- •Red blood cell transfusion within 8 weeks prior to randomization.
- •Any erythropoietic stimulating agent within 8 weeks prior to randomization
- •Uncontrolled hypertension
- •Severe heart failure at Screening (New York Heart Association Class IV)
- •Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening
- •Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients
Arms & Interventions
Vadadustat
Intervention: Vadadustat (Drug)
Darbepoetin alfa
Intervention: Darbepoetin alfa (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
Time Frame: Baseline; Weeks 24 to 36
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline Hb concentration (\<9.5 versus ≥9.5 grams per deciliter \[g/dL\]), geographic region (United States \[US\] versus European Union \[EU\] versus Rest of World \[ROW\]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 \[no CHF\] or I versus II or III) as covariates.
Median Time to First Major Adverse Cardiovascular Event (MACE)
Time Frame: Up to Week 208
MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
Secondary Outcomes
- Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)(Baseline; Weeks 40 to 52)
- Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis(Up to Week 208)
- Median Time to First Cardiovascular MACE(Up to Week 208)
- Median Time to First Cardiovascular Death(Up to Week 208)
- Median Time to First All-cause Mortality(Up to Week 208)