Clinical trial NCT04313153: 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)
Official title: Phase 3b, Randomized, Open-label, Active-controlled 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Keywords: vadadustat
hemodialysis
erythropoiesis-stimulating agents
darbepoetin alfa
CKD
Anemia
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2020-03-18
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
timeFrame: Baseline; Weeks 20 to 26
Secondary outcomes:
measure: Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)
timeFrame: Baseline; Weeks 46 to 52
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Granada Hills
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Lynwood
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: San Dimas
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Middlebury
country: United States
facility: Research Site
state: Connecticut
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Pontiac
country: United States
facility: Research Site
state: Michigan
city: Roseville
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Brookhaven
country: United States
facility: Research Site
state: Mississippi
city: Tupelo
country: United States
facility: Research Site
state: Mississippi
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Kinston
country: United States
facility: Research Site
state: North Carolina
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: Bethlehem
country: United States
facility: Research Site
state: Pennsylvania
city: Orangeburg
country: United States
facility: Research Site
state: South Carolina
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: McAllen
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Hampton
country: United States
facility: Research Site
state: Virginia
city: Mariánské Lázně
country: Czechia
facility: Research Site
city: Nový Jičín
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha 9
country: Czechia
facility: Research Site
city: Příbram
country: Czechia
facility: Research Site
city: Slaný
country: Czechia
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Kaposvar
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Vicenza
country: Italy
facility: Research Site
city: Biała Podlaska
country: Poland
facility: Research Site
city: Brodnica
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Pszczyna
country: Poland
facility: Research Site
city: Sochaczew
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site #2
city: Valencia
country: Spain
facility: Research Site
Study officials:
affiliation: Akebia Therapeutics Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
citation: Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.