Clinical trial NCT02865850: Efficacy and Safety Study to Evaluate Vadadustat for the Correction or Maintenance Treatment of Anemia in Participants With Incident Dialysis-dependent Chronic Kidney Disease (DD-CKD)
Official title: Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - CORRECTION/CONVERSION)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Dialysis-Dependent Chronic Kidney Disease
Keywords: Vadadustat
AKB-6548
anemia
chronic kidney disease
CKD
chronic renal insufficiency
renal impairment
erythropoietin
kidney
renal
oral anemia treatment
hemoglobin
hypoxia-inducible factor
HIF
efficacy
safety
phase 3
cardiovascular
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-08-15
Enrollment: 369
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: A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction or maintenance treatment of anemia in participants with incident dialysis-dependent chronic kidney disease (DD-CKD).

Detailed description: This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the correction or maintenance treatment in participants with anemia secondary to chronic kidney disease who have recently initiated dialysis treatment for end-stage renal disease.

Eligibility criteria: Inclusion Criteria:

* ≥18 years of age
* Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
* Mean Screening hemoglobin between 8.0 and \<11.0 grams per deciliter (g/dL) (inclusive)
* Serum ferritin ≥100 nanograms per deciliter (ng/mL) and TSAT ≥20% during Screening

Exclusion Criteria:

* Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
* Red blood cells transfusion within 8 weeks prior to randomization
* Anticipated to recover adequate kidney function to no longer require dialysis
* Uncontrolled hypertension
* Severe heart failure at Screening (New York Heart Association Class IV)
* Acute coronary syndrome (hospitalization for unstable angina, 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 congestive heart failure; or stroke within 12 weeks prior to or during Screening.
* Participants meeting the criteria of erythropoiesis-stimulating agent resistance within 8 weeks prior to or during Screening defined as follows

  1. epoetin: \> 7700 units/dose three times per week or \>23,000 units per week
  2. Darbepoetin alfa: \>100 micrograms per week (mcg/week)
  3. methoxy polyethylene glycol-epoetin beta: \>100 micrograms (mcg) every other week or \>200 mcg/month
* Hypersensitivity to Vadadustat, Darbepoetin alfa or any of their excipients

Primary outcomes:
measure: Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
timeFrame: Baseline; Weeks 24 to 36
measure: Median Time to First Major Adverse Cardiovascular Event (MACE)
timeFrame: Up to 176 weeks
Secondary outcomes:
measure: Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)
timeFrame: Baseline; Weeks 40 to 52
measure: Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis
timeFrame: Up to 176 weeks
measure: Median Time to First Cardiovascular MACE
timeFrame: Up to 176 weeks
measure: Median Time to First Cardiovascular Death
timeFrame: Up to 176 weeks
measure: Median Time to First All-cause Mortality
timeFrame: Up to 176 weeks
Other outcomes:
measure: Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
timeFrame: Weeks 24 to 36
measure: Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
timeFrame: Weeks 24 to 36
measure: Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
timeFrame: Weeks 40 to 52
measure: Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
timeFrame: Weeks 40 to 52
measure: Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit
timeFrame: Baseline; up to Week 52
measure: Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit
timeFrame: Baseline; up to Week 52
measure: Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure
timeFrame: Baseline; Weeks 24 to 36
measure: Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron
timeFrame: Up to Week 52
measure: Exploratory - Proportion of Participants Receiving IV Iron Therapy
timeFrame: Up to Week 52
measure: Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s)
timeFrame: Up to Week 52
Locations:
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Canyon Country
country: United States
facility: Research Site
state: California
city: Downey
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Research Site
state: California
city: Granada Hills
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
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state: California
city: Long Beach
country: United States
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state: California
city: Los Angeles
country: United States
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state: California
city: Montebello
country: United States
facility: Research Site
state: California
city: Monterey Park
country: United States
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state: California
city: Newhall
country: United States
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state: California
city: Northridge
country: United States
facility: Research Site #1
state: California
city: Northridge
country: United States
facility: Research Site #2
state: California
city: Riverside
country: United States
facility: Research Site
state: California
city: Riverside
country: United States
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state: California
city: Sacramento
country: United States
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state: California
city: San Diego
country: United States
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state: California
city: San Dimas
country: United States
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state: California
city: Whittier
country: United States
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state: California
city: Arvada
country: United States
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state: Colorado
city: Westminster
country: United States
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state: Colorado
city: Stamford
country: United States
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state: Connecticut
city: Coral Gables
country: United States
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state: Florida
city: Coral Springs
country: United States
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state: Florida
city: Lauderdale Lakes
country: United States
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state: Florida
city: Miami Beach
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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city: Winter Park
country: United States
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state: Florida
city: Augusta
country: United States
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state: Georgia
city: Columbus
country: United States
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state: Georgia
city: Lawrenceville
country: United States
facility: Research Site #2
state: Georgia
city: Statesboro
country: United States
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state: Georgia
city: Meridian
country: United States
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state: Idaho
city: Takoma Park
country: United States
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state: Maryland
city: Roseville
country: United States
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state: Michigan
city: Kansas City
country: United States
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state: Missouri
city: Albuquerque
country: United States
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state: New Mexico
city: Astoria
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state: New York
city: Winston-Salem
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state: North Carolina
city: Philadelphia
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state: Pennsylvania
city: Chattanooga
country: United States
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state: Tennessee
city: Chattanooga
country: United States
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state: Tennessee
city: Knoxville
country: United States
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state: Tennessee
city: Nashville
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state: Tennessee
city: Arlington
country: United States
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state: Texas
city: El Paso
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: Hampton
country: United States
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state: Virginia
city: Bahia Blanca
country: Argentina
facility: Research Site
state: Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
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state: Buenos Aires
city: Junin
country: Argentina
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state: Buenos Aires
city: Pergamino
country: Argentina
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state: Buenos Aires
city: Temperley
country: Argentina
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state: Buenos Aires
city: Cordoba
country: Argentina
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city: Corrientes
country: Argentina
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city: Salta
country: Argentina
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city: San Luis
country: Argentina
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city: Fortaleza
country: Brazil
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state: Ceará
city: Belo Horizonte
country: Brazil
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state: Minas Gerais
city: Juiz de Fora
country: Brazil
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state: Minas Gerais
city: Curitiba
country: Brazil
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state: Paraná
city: Maringá
country: Brazil
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state: Paraná
city: Canoas
country: Brazil
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state: Rio Grande Do Sul
city: Passo Fundo
country: Brazil
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state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
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state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
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state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Research Site
state: Santa Catarina
city: Santo André
country: Brazil
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state: Sao Paulo
city: São Bernardo do Campo
country: Brazil
facility: Research Site
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Research Site
state: Sao Paulo
city: Villingen-Schwenningen
country: Germany
facility: Research Site
state: Baden Wuerttemberg
city: Rostock
country: Germany
facility: Research Site
state: Mecklenburg Vorpommern
city: Duesseldorf
country: Germany
facility: Research Site
state: Nordrhein Westfalen
city: San Giovanni Rotondo
country: Italy
facility: Research Site
state: Foggia
city: Genova
country: Italy
facility: Research Site
city: Lecco
country: Italy
facility: Research Site
city: Napoli
country: Italy
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city: Pavia
country: Italy
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city: Roma
country: Italy
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city: Siena
country: Italy
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city: Chuncheon
country: Korea, Republic of
facility: Research Site
state: Gangwon-do
city: Seongnam-si,
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Zapopan
country: Mexico
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state: Jalisco
city: Morelia
country: Mexico
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state: Michoacán
city: Culiacan
country: Mexico
facility: Research Site
state: Sinaloa
city: Golub Dobrzyn
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Leiria
country: Portugal
facility: Research Site
city: Loures
country: Portugal
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site #2
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Brovary
country: Ukraine
facility: Research Site
city: Cherkassy
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Mykolaiv
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Zhytomyr
country: Ukraine
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.
citation: Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.