AnemiaPhase 3NCT04313153

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)

A Phase 3 study testing Vadadustat and Darbepoetin alfa in people with Anemia, run by Akebia Therapeutics at 59 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Anemia
What is being tested?: Vadadustat and Darbepoetin alfa
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 319 participants
Where: 59 sitesin 6 countries
Study dates: 27 May 2020to 22 Jun 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:
Hb values between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States;
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

Who cannot join

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
Methoxy polyethylene glycol-epoetin beta > 50 micrograms (µg)/week;
Darbepoetin alfa > 100 µg/week;
Epoetin analogues > 23000 International Units (IU)/week
Active bleeding or recent blood loss within 8 weeks prior to randomization

Show all 10Show fewer

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

Trial locations and contacts

59 sites in 6 countries.

Country

City, postcode or hospital

59 sites in 6 countries

United States39 sites

Research Site
Albuquerque, New Mexico, 87109
Research Site
Austin, Texas, 78751
Research Site
Austin, Texas, 78758
Research Site
Bethlehem, Pennsylvania, 18017
Research Site
Brookhaven, Mississippi, 39601
Research Site
Chattanooga, Tennessee, 37404
Research Site
Chula Vista, California, 91910
Research Site
Coral Gables, Florida, 33134
Research Site
Denver, Colorado, 80230
Research Site
Durham, North Carolina, 27704
Research Site
El Paso, Texas, 79902
Research Site
Granada Hills, California, 91344
Research Site
Hampton, Virginia, 23666
Research Site
Houston, Texas, 77004
Research Site
Houston, Texas, 77099
Research Site
Kansas City, Missouri, 64111
Research Site
Kinston, North Carolina, 28504
Research Site
Knoxville, Tennessee, 37920
Research Site
Knoxville, Tennessee, 37923
Research Site
Las Vegas, Nevada, 89128
Research Site
Los Angeles, California, 90022
Research Site
Lynwood, California, 90262
Research Site
McAllen, Texas, 78503
Research Site
Middlebury, Connecticut, 06762
Research Site
Minneapolis, Minnesota, 55404
Research Site
New Bern, North Carolina, 28562
Research Site
Northridge, California, 91324
Research Site
Orangeburg, South Carolina, 29118
Research Site
Pontiac, Michigan, 48341
Research Site
Roseville, Michigan, 48066
Research Site
San Antonio, Texas, 78204
Research Site
San Antonio, Texas, 78212
Research Site
San Antonio, Texas, 78229
Research Site
San Dimas, California, 91773
Research Site
St Louis, Missouri, 63136
Research Site
Tampa, Florida, 33614
Research Site
Tupelo, Mississippi, 38801
Research Site
Whittier, California, 90603
Research Site
Winter Park, Florida, 32789

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Czechia6 sites

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Pilsen
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Hungary5 sites

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Poland5 sites

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Italy2 sites

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Spain2 sites

Research Site #2
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About this study

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)

Read the detailed description

This study consists of three periods:

Screening Period
Conversion and Maintenance Treatment Period
Safety Follow-up Period

Individual participants will participate in total trial duration of approximately 64 weeks.

Conditions: Anemia
Being tested: Vadadustat, Darbepoetin alfa
Keywords: vadadustat, hemodialysis, erythropoiesis-stimulating agents, darbepoetin alfa, CKD, Anemia
Medical subject headings: Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VadadustatDrug
oral tablets
Darbepoetin alfaDrug
intravenous or subcutaneous solution

Study groups in NCT04313153
Study group	Role	What they receive
Vadadustat once daily (QD)	Experimental	Not described Receives: Drug: Vadadustat
Vadadustat three times weekly (TIW)	Experimental	Not described Receives: Drug: Vadadustat
Darbepoetin alfa	Active comparator	Not described Receives: Drug: Darbepoetin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
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 PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. 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.
Measured: Baseline; Weeks 20 to 26

Secondary outcomes (1)

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, regardless of intercurrent events. 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.
Measured: Baseline; Weeks 46 to 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 May 202022 Jun 2022

First posted18 Mar 2020
Study start27 May 2020
Primary completion26 Nov 2021
Study completion22 Jun 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for AnemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 319 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04313153
Sponsor's protocol ID: 404-201-00012
Other IDs: AKB-6548-CI-0036, 2019-004851-36, 2019
Status last verified: May 2025
First submitted: 16 Mar 2020
Last updated: 22 May 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Kooienga L, Burke S, Kathresal A, Luo W, Yang Z, Zhang Z, Zwiech R, Hernandez GT. Safety and Efficacy of Vadadustat Once Daily and Three Times Weekly in Patients With Dialysis-Dependent CKD With Anemia. Kidney360. 2024 Nov 1;5(11):1652-1661. doi: 10.34067/KID.0000000567. Epub 2024 Sep 4.
PubMed 39231617
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.
PubMed 36005278

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
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Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
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Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingPhase 3
A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions
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Active, not recruitingPhase 1
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All Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT04313153
Acronym / sponsor ID: 404-201-00012
Conditions: Anemia
Keywords: vadadustat, hemodialysis, erythropoiesis-stimulating agents, darbepoetin alfa, CKD, Anemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 319 participants (actual)
Lead sponsor: Akebia TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.
Study start: 27 May 2020 (actual)
Primary completion: 26 Nov 2021 (actual)
Study completion: 22 Jun 2022 (actual)
First posted: 18 Mar 2020 (actual)
Results: Posted 22 May 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This study consists of three periods:

Screening Period
Conversion and Maintenance Treatment Period
Safety Follow-up Period

Individual participants will participate in total trial duration of approximately 64 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Vadadustat once daily (QD)	Experimental	Drug: Vadadustat
Vadadustat three times weekly (TIW)	Experimental	Drug: Vadadustat
Darbepoetin alfa	Active comparator	Drug: Darbepoetin alfa

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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:
Serum ferritin ≥ 100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥ 20% during Screening

Key exclusion criteria (10 listed)

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
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Vadadustatoral tablets	Drug	Vadadustat once daily (QD), Vadadustat three times weekly (TIW)
Darbepoetin alfaintravenous or subcutaneous solution	Drug	Darbepoetin alfa

Primary outcome

Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)
Time frame: Baseline; Weeks 20 to 26
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 PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. 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.

1 secondary outcome

Change From Baseline in Hb to the Average Over the Secondary Evaluation Period (SEP) (Weeks 46 to 52)
Time frame: Baseline; Weeks 46 to 52

Results and safety

Results posted to the registry on 22 May 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vadadustat QD	105	54
Vadadustat TIW	106	50
Darbepoetin Alfa	108	67

Primary outcome: Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26)

Time frame: Baseline; Weeks 20 to 26. Least squares mean (Standard Error). Unit: Grams per deciliter (g/dL)

Measure	Vadadustat QD n = 105	Vadadustat TIW n = 106	Darbepoetin Alfa n = 108
Value	0.07 (0.12)	-0.19 (0.12)	0.34 (0.12)

Population analysed: Randomized Population

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first dose of study drug (Day 1) up to Week 56 (from first dose of study drug to last dose + 4 weeks of follow-up). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vadadustat QD	47 of 105 (44.8%)	46 of 105 (43.8%)	12 of 105
Vadadustat TIW	47 of 104 (45.2%)	49 of 104 (47.1%)	9 of 104
Darbepoetin Alfa	47 of 108 (43.5%)	46 of 108 (42.6%)	7 of 108

Limitations and caveats (from the sponsor): Per the protocol, data was collected by the arm to which participants were randomized and not by dose received in vadadustat QD or vadadustat TIW arms.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39231617Kooienga L, Burke S, Kathresal A, Luo W, Yang Z, Zhang Z, Zwiech R, Hernandez GT. Safety and Efficacy of Vadadustat Once Daily and Three Times Weekly in Patients With Dialysis-Dependent CKD With Anemia. Kidney360. 2024 Nov 1;5(11):1652-1661. doi: 10.34067/KID.0000000567. Epub 2024 Sep 4.
Derived from this study: PubMed 36005278Natale 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.
Individual participant dataSharing planned: No

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Active, not recruitingPhase 1/2
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RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
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Myelodysplastic Syndromes
RecruitingPhase 3
A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions
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Active, not recruitingPhase 1
A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Chief Medical Officer study director

Akebia Therapeutics

59 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vadadustat and Darbepoetin alfa in people with Anemia, run by Akebia Therapeutics at 59 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Czechia, Hungary, Poland, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Hb to the Average Over the Primary Evaluation Period (PEP) (Weeks 20 to 26) (time frame: Baseline; Weeks 20 to 26). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04313153, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025; AzTrials last refreshed its copy on 8 Nov 2026.