Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects

Phase 3

Completed

• Conditions: Anemia Associated With Chronic Kidney Disease (CKD)
• Interventions: Drug: Vadadustat; Drug: Mircera®

• Registration Number: NCT04707768
• Lead Sponsor: Akebia Therapeutics

Brief Summary

This study will be conducted to demonstrate the efficacy and safety of vadadustat administered three times weekly (TIW) compared to a long-acting erythropoiesis-stimulating agent (ESA) (Mircera®) for the maintenance treatment of anemia in hemodialysis participants.

Detailed Description

Following randomization, there will be 2 periods during the study:

* Conversion and Maintenance Period (Weeks 0 to 52): There will be a primary efficacy evaluation period (Weeks 20 to 26) and a secondary efficacy evaluation period (Weeks 46 to 52).

* Safety Follow-up Period (Early Termination \[ET\] and Follow-Up): post-treatment safety follow-up visit (ET/End of Treatment \[EOT\] +4 weeks) either in person or via telephone.

Study Timeline

• Study First Submitted: 2021-01-12
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-13
• Study Start: 2021-06-18
• Primary Completion: 2023-01-06
• Study Completion: 2023-01-30
• Disposition First Submitted: 2023-12-14
• Disposition First Posted: 2023-12-18
• Status Verified: 2024-12
• Results First Submitted: 2024-12-23
• Results First Submitted QC: 2024-12-23
• Last Update Submitted: 2024-12-23
• Results First Posted: 2025-01-15
• Last Update Posted: 2025-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 456

Inclusion Criteria

• ≥18 years of age
• Receiving chronic, outpatient in-center hemodialysis three times weekly (TIW) for end-stage kidney disease for at least 12 weeks prior to Screening Visit 1 (SV1)
• Currently maintained on Mircera® (≤250 μg/month) with at least 2 doses received within 8 weeks prior to Screening Visit 2 (SV2)
• Mean Screening hemoglobin (Hb) between 8.5 and 11.0 grams per deciliter (g/dL) (inclusive), as determined by the average of 2 Hb values measured by the central laboratory at least 4 days apart between SV1 and SV2
• Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
• Folate and vitamin B12 measurements ≥ lower limit of normal during Screening

Exclusion Criteria

• Anemia due to a cause other than chronic kidney disease (CKD).
• Clinically meaningful bleeding event within 8 weeks prior to Baseline
• Red blood cell (RBC) transfusion within 8 weeks prior to Baseline
• Having received any doses of darbepoetin alfa (Aranesp®) within 4 weeks prior to Baseline
• Having received any doses of epoetin alfa (Epogen®) within 1 week prior to Baseline.
• Current uncontrolled hypertension.
• 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 (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening.
• Known hypersensitivity to vadadustat, Mircera®, or any of their excipients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vadadustat high dose	Vadadustat	Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 900 mg.
Mircera®	Mircera®	Participants will continue to receive Mircera® for up to 52 weeks.
Vadadustat low dose	Vadadustat	Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 600 milligrams (mg).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)	Baseline; Weeks 20 to 26	The Baseline Hb was defined as the average of last 2 central laboratory Hb measurements of samples taken at or prior to the first dose. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)	Baseline; Weeks 46 to 52	The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value.

Trial Locations

Locations (3)

Research Site; 🇺🇸 Woodbridge, Virginia, United States

Research Site#1; 🇺🇸 Coral Springs, Florida, United States

Research Site#2; 🇺🇸 Coral Springs, Florida, United States