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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Open-label, Active-controlled 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

Conditions
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Anemia Associated With Chronic Kidney Disease (CKD)

Intervention / Treatment
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* Drug: Vadadustat
* Drug: Mircera®


Participation Criteria
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Eligibility Criteria
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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® 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vadadustat low dose<br>Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 600 milligrams (mg). | Drug: Vadadustat<br>* oral tablets<br>|
| Experimental: Vadadustat high dose<br>Participants previously receiving Mircera® received vadadustat for up to 52 weeks with an initial dose of 900 mg. | Drug: Vadadustat<br>* oral tablets<br>|
| Active Comparator: Mircera®<br>Participants will continue to receive Mircera® for up to 52 weeks. | Drug: Mircera®<br>* intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in hemoglobin (Hb) between Baseline (average pretreatment Hb) and the primary evaluation period (average Hb from Weeks 20 to 26, inclusive) |  | Baseline; Weeks 20-26 | 
| Number of participants with treatment-emergent non-serious adverse events and treatment-emergent serious adverse events |  | up to Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in Hb between Baseline (average pretreatment Hb) and the secondary evaluation period (average Hb from Weeks 46 to 52, inclusive) |  | Baseline; Weeks 46-52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Chronic Kidney Disease, CKD, Hemodialysis, Vadadustat, Erythropoiesis-stimulating agent (ESA)