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

Akebia Therapeutics

Status and phase: Completed; Phase 3

Conditions: Anemia Associated With Chronic Kidney Disease (CKD)

Treatments: Drug: Vadadustat; Drug: Mircera®

Study type: Interventional

Funder types: Industry

Identifiers

NCT04707768

AKB-6548-CI-0039

Details and patient eligibility

About

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.

Full 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.

Enrollment: 456 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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456 participants in 3 patient groups

Vadadustat low dose

Experimental group

Description:

Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 600 milligrams (mg).

Treatment:

Drug: Vadadustat

Vadadustat high dose

Experimental group

Description:

Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 900 mg.

Treatment:

Drug: Vadadustat

Mircera®

Active Comparator group

Description:

Participants will continue to receive Mircera® for up to 52 weeks.

Treatment:

Drug: Mircera®