Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting From Erythropoiesis-Stimulating Agents (ESAs)

Akebia Therapeutics

Status and phase: Completed; Phase 3

Conditions: Anemia

Treatments: Drug: Darbepoetin alfa; Drug: Vadadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT04313153

AKB-6548-CI-0036 (Other Identifier)

2019-004851-36 (EudraCT Number)

404-201-00012

Details and patient eligibility

About

This trial will be conducted to demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in hemodialysis participants after conversion from current erythropoiesis-stimulating agent (ESA) therapy.

Full description

This study consists of three periods:

1. Screening Period
2. Conversion and Maintenance Treatment Period
3. Safety Follow-up Period

Individual participants will participate in total trial duration of approximately 64 weeks.

Enrollment: 319 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Receiving chronic, outpatient three times weekly (TIW) in-center hemodialysis for end-stage renal disease for at least 12 weeks prior to Screening

• Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥ 1.2 using the most recent historical measurement within 8 weeks prior to or during Screening

• Use of any approved erythropoiesis-stimulating agents (ESAs) for at least the 8 weeks prior to Screening Visit 2

• Two hemoglobin (Hb) values, at least 4 days apart, measured by the central laboratory during Screening within the following prespecified ranges:

  1. Hb values between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States;
  2. Hb values between 9.0 and 12.0 g/dL (inclusive) in Europe

• 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 (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)

• Participants meeting cut-off of the following equivalent mean weekly doses calculated over 8 weeks prior to Screening Visit 2

  1. Methoxy polyethylene glycol-epoetin beta > 50 micrograms (µg)/week;
  2. Darbepoetin alfa > 100 µg/week;
  3. Epoetin analogues > 23000 International Units (IU)/week

• Active bleeding or recent blood loss within 8 weeks prior to randomization

• Red blood cell transfusion within 8 weeks prior to randomization

• 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, darbepoetin alfa, or any of their excipients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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319 participants in 3 patient groups

Vadadustat once daily (QD)

Experimental group

Treatment:

Drug: Vadadustat

Vadadustat three times weekly (TIW)

Experimental group

Treatment:

Drug: Vadadustat

Darbepoetin alfa

Active Comparator group

Treatment:

Drug: Darbepoetin alfa