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

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia Associated With Chronic Kidney Disease (CKD)
• Intervention / Treatment: Drug: Vadadustat; Drug: Mircera®

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.

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85035
      • Research Site
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • Research Site
  • California
    • El Centro, California, United States, 92243
      • Research Site
    • Escondido, California, United States, 92025
      • Research Site
    • Fresno, California, United States, 93720
      • Research Site
    • Granada Hills, California, United States, 91344
      • Research Site
    • Porterville, California, United States, 93257
      • Research Site
    • San Diego, California, United States, 92111
      • Research Site
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Research Site
    • Denver, Colorado, United States, 80210
      • Research Site
  • Delaware
    • Hockessin, Delaware, United States, 19707
      • Research Site
  • Florida
    • Bradenton, Florida, United States, 34209
      • Research Site
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Coral Springs, Florida, United States, 33071
      • Research Site#1
    • Coral Springs, Florida, United States, 33071
      • Research Site#2
    • Jacksonville, Florida, United States, 32216
      • Research Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Research Site
    • Buford, Georgia, United States, 30518
      • Research Site
    • Dalton, Georgia, United States, 30720
      • Research Site
    • Macon, Georgia, United States, 31201
      • Research Site
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70884
      • Research Site
    • Shreveport, Louisiana, United States, 71101
      • Research Site
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Research Site
    • Springfield, Massachusetts, United States, 01107
      • Research Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Research Site
    • Rochester Hills, Michigan, United States, 48309
      • Research Site
    • Saint Clair Shores, Michigan, United States, 48081
      • Research Site
  • Mississippi
    • Brookhaven, Mississippi, United States, 39601
      • Research Site
    • Columbus, Mississippi, United States, 39705
      • Research Site
    • Tupelo, Mississippi, United States, 38801
      • Research Site
  • Nebraska
    • North Platte, Nebraska, United States, 69101
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89115
      • Research Site
    • Reno, Nevada, United States, 89511
      • Research Site
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Research Site
    • Gallup, New Mexico, United States, 87301
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Durham, North Carolina, United States, 27704
      • Research Site
    • Kinston, North Carolina, United States, 28504
      • Research Site
    • Raleigh, North Carolina, United States, 27609
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Pennsylvania
    • Kittanning, Pennsylvania, United States, 16201
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Research Site
  • Texas
    • Arlington, Texas, United States, 76015
      • Research Site
    • Austin, Texas, United States, 78758
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Dallas, Texas, United States, 75230
      • Research Site
    • Houston, Texas, United States, 77074
      • Research Site
    • Houston, Texas, United States, 77099
      • Research Site
    • Mansfield, Texas, United States, 76063
      • Research Site
    • Mission, Texas, United States, 78572
      • Research Site
    • San Antonio, Texas, United States, 78251
      • Research Site
    • San Antonio, Texas, United States, 78211
      • Research Site
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Research Site
    • Salem, Virginia, United States, 24153
      • Research Site
    • Woodbridge, Virginia, United States, 22192
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)	The Baseline Hb was defined as the average of last 2 central laboratory Hb measurements of samples taken at or prior to the first dose. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value.	Baseline; Weeks 20 to 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)	The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value.	Baseline; Weeks 46 to 52

Collaborators and Investigators

• Sponsor: Akebia Therapeutics
• Investigators: Study Director: Chief Medical Officer, Akebia Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Actual): January 6, 2023
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Anemia; Chronic Kidney Disease; CKD; Hemodialysis; Vadadustat; Erythropoiesis-stimulating agent (ESA)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: AKB-6548-CI-0039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No