To Evaluate the Efficacy of Three Times Weekly (TIW) Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis

A Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy of Three Times Weekly Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis

This is a multi-center, randomized (1:1), open-label, active-controlled, pragmatic study of the efficacy of vadadustat administered three times a week compared to standard of care erythropoiesis-stimulating agent for the treatment of anemia in in-center hemodialysis participants with end-stage kidney disease (ESKD). A subset of sites will participate in a red blood cell (RBC) sub-study where changes in the phenotype of RBCs in response to vadadustat treatment relative to methoxy polyethylene glycol-epoetin beta treatment in DD-CKD participants with anemia will be assessed. A separate informed consent form (ICF) will be signed by these participants who opt to be in the RBC sub-study. Of the 350 participants in the main study, approximately 28 participants will also be enrolled into the RBC sub-study. The total duration of the study is approximately 35 Weeks including screening and follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Anemia of Chronic Kidney Disease
• Intervention / Treatment: Drug: Vadadustat; Drug: Erythropoiesis-Stimulating Agent (ESA)

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36117-7306
      • DaVita Research Site
  • Connecticut
    • Hartford, Connecticut, United States, 06112-1260
      • DaVita Research Site
    • Middlebury, Connecticut, United States, 06705-3893
      • DaVita Research Site
  • Georgia
    • Columbus, Georgia, United States, 31904-3604
      • DaVita Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435-1807
      • DaVita Research Site #1
    • Minneapolis, Minnesota, United States, 55435-1807
      • DaVita Research Site
  • Nevada
    • Henderson, Nevada, United States, 89052-5548
      • DaVita Research Site
    • Las Vegas, Nevada, United States, 89128-0804
      • DaVita Research Site
  • Texas
    • El Paso, Texas, United States, 79835-2200
      • DaVita Research Site #1
    • El Paso, Texas, United States, 79835-2200
      • DaVita Research Site
    • Houston, Texas, United States, 77054-3836
      • DaVita Research Site #1
    • Houston, Texas, United States, 77054-3836
      • DaVita Research Site
    • San Antonio, Texas, United States, 78258-4800
      • DaVita Research Site #1
    • San Antonio, Texas, United States, 78258-4800
      • DaVita Research Site #2
    • San Antonio, Texas, United States, 78258-4800
      • DaVita Research Site
    • The Woodlands, Texas, United States, 77384-3024
      • DaVita Research Site
  • Virginia
    • Norfolk, Virginia, United States, 23502-3235
      • DaVita Research Site #1
    • Norfolk, Virginia, United States, 23502-3235
      • DaVita Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult participants ≥18 years of age.
• Receiving outpatient in-center hemodialysis for ESKD at least three times a week.
• Currently prescribed or meets criteria for ESA based on approved facility policy.
• Hb > 8 grams per deciliter (g/dl).
• Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20%.
• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.
• For selected sites, individuals who opt to participate in the RBC sub-study must meet the following inclusion criteria:
• Currently prescribed or will be prescribed methoxy polyethylene glycol-epoetin beta.
• Hb <11.5 g/dL

Exclusion Criteria:

• Contraindication to receive vadadustat per United States prescribing information (USPI) as determined by the treating health care provider.
• Concomitant use of any hypoxia-inducible factor prolyl hydroxylase inhibitor(HIF-PHI).
• Known cirrhosis or active, acute liver disease.
• Unable to comply with study requirements or compliance with attending dialysis treatments as prescribed, or in the opinion of the treating physician or Investigator, not clinically stable to participate in the study.
• Pregnant at the time of consent (per participant self-report).
• Any other reason, which in the opinion of the Investigator, would make the participants unsuitable for participation in the study.
• For selected sites, individuals who opt to participate in the RBC sub-study must also not meet the following exclusion criteria:
• History of, or currently diagnosed with, any hematological disease, such as sickle cell disease, thalassemia, hemochromatosis, Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, myelodysplastic syndromes, or any other blood disorder that could interfere with the study outcomes.
• Participants will receive a blood transfusion within 3 months prior to the initiation of the study.
• History of or currently diagnosed with chronic lung disease

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vadadustat; Study drug will be administered three times a week.	Drug: Vadadustat; 300mg, oral tablets; Other Names: AKB-6548; Vafseo
Active Comparator: Erythropoiesis-Stimulating Agent (ESA); Dose adjustments will be determined by hemoglobin (Hb) change and current dose of ESA, per ESA dosing protocol	Drug: Erythropoiesis-Stimulating Agent (ESA); Administered by intra-venous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in hemoglobin (Hb)	Baseline and the mean of Week 20 to 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants reporting treatment-emergent serious adverse events (TESAEs)	Up to 29 Weeks
Proportion of participants with mean Hb levels within target range	Week 16 to Week 24
Proportion of participants receiving RBC transfusions	Up to 29 Weeks

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Open-label; Chronic Kidney Disease; Hemodialysis; Vadadustat; Erythropoiesis-Stimulating Agent
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hematologic Agents; Hematinics; vadadustat
• Other Study ID Numbers: AKB-6548-CI-0052; VOCAL (Other Identifier: Akebia Therapeutics)

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