Clinical trial NCT04707768: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia Associated With Chronic Kidney Disease (CKD)
Keywords: Anemia
Chronic Kidney Disease
CKD
Hemodialysis
Vadadustat
Erythropoiesis-stimulating agent (ESA)
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-01-13
Enrollment: 456
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 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin (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: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Pine Bluff
country: United States
facility: Research Site
state: Arkansas
city: El Centro
country: United States
facility: Research Site
state: California
city: Escondido
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: Granada Hills
country: United States
facility: Research Site
state: California
city: Porterville
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Arvada
country: United States
facility: Research Site
state: Colorado
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Hockessin
country: United States
facility: Research Site
state: Delaware
city: Bradenton
country: United States
facility: Research Site
state: Florida
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Coral Springs
country: United States
facility: Research Site#1
state: Florida
city: Coral Springs
country: United States
facility: Research Site#2
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Buford
country: United States
facility: Research Site
state: Georgia
city: Dalton
country: United States
facility: Research Site
state: Georgia
city: Macon
country: United States
facility: Research Site
state: Georgia
city: Nampa
country: United States
facility: Research Site
state: Idaho
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Plymouth
country: United States
facility: Research Site
state: Massachusetts
city: Springfield
country: United States
facility: Research Site
state: Massachusetts
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Rochester Hills
country: United States
facility: Research Site
state: Michigan
city: Saint Clair Shores
country: United States
facility: Research Site
state: Michigan
city: Brookhaven
country: United States
facility: Research Site
state: Mississippi
city: Columbus
country: United States
facility: Research Site
state: Mississippi
city: Tupelo
country: United States
facility: Research Site
state: Mississippi
city: North Platte
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Reno
country: United States
facility: Research Site
state: Nevada
city: Portsmouth
country: United States
facility: Research Site
state: New Hampshire
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Gallup
country: United States
facility: Research Site
state: New Mexico
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Kinston
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Kittanning
country: United States
facility: Research Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Arlington
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
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: Mansfield
country: United States
facility: Research Site
state: Texas
city: Mission
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: Alexandria
country: United States
facility: Research Site
state: Virginia
city: Salem
country: United States
facility: Research Site
state: Virginia
city: Woodbridge
country: United States
facility: Research Site
state: Virginia
Study officials:
affiliation: Akebia Therapeutics Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: