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)

Anemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04313153
• Other study ID #: 404-201-00012
• Secondary ID: AKB-6548-CI-0036
• Status: Completed
• Phase: Phase 3
• Start date: May 27, 2020
• Est. completion date: June 22, 2022

Study information

• Verified date: November 2022
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Description:

This study consists of three periods:

1. Screening Period

2. Conversion and Maintenance Treatment Period

3. Safety Follow-up Period

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 319
• Est. completion date: June 22, 2022
• Est. primary completion date: November 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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:

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

2. 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

Exclusion Criteria:

• Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP). If employing birth control, 2 of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, or birth control.

• Male participants who have not had a vasectomy and do not agree to the following: use of an acceptable form of contraception during the study and for 30 days after the last dose of the study drug; to not donate semen during the study and for at least 30 days after the last dose of vadadustat

• Women who are breast feeding and/or who have a positive pregnancy test result prior to receiving IMP

• Participants with contraindication to required trial assessment

• Participants who, is in opinion of the investigator or medical monitor, have a medical history or medical findings inconsistent with safety or trial compliance

• 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

1. Methoxy polyethylene glycol-epoetin beta > 50 micrograms (µg)/week;

2. Darbepoetin alfa > 100 µg/week;

3. Epoetin analogues > 23000 International Units (IU)/week

• Active bleeding or recent blood loss within 8 weeks prior to randomization

• Red blood cell transfusion within 8 weeks prior to randomization

• Anticipated to discontinue hemodialysis during the trial

• Judged by the investigator that the participant is likely to need rescue therapy (ESA administration or red blood cell [RBC] transfusion) immediately after enrollment in the trial

• History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver)

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin > 1.5 x upper limit of normal during Screening. Participants with a history of Gilbert's syndrome are not excluded.

• Current uncontrolled hypertension as determined by the investigator that would contraindicate the use of an ESA

• 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

• History of new or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ are not excluded.

• History of a new or recurrent episode of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening

• History of hemosiderosis or hemochromatosis

• History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded)

• Scheduled organ transplant from a living donor and subjects on the kidney transplant wait-list who are expected to receive a transplant within 6 months

• History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)

• Known hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients

• Use of an investigational medication within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to screening or during screening and any prior use of a hypoxia-inducible factor prolyl hydroxylase inhibitor. Participants may participate in another concurrent trial only if that trial is a non-interventional, observational investigation.

• Participants with bilateral native nephrectomy

• Treated with probenecid within the 28-day Screening Period prior to randomization or during the study treatment duration

• Any other reason, which in the opinion of the investigator, would make the participant not suitable for participation in the trial

Related Conditions & MeSH terms

• Anemia

Intervention

Drug:
• Vadadustat
oral tablets
• Darbepoetin alfa
intravenous or subcutaneous solution

Locations

Country	Name	City	State
Czechia	Research Site	Mariánské Lázne
Czechia	Research Site	Nový Jicín
Czechia	Research Site	Plzen
Czechia	Research Site	Praha 9
Czechia	Research Site	Príbram
Czechia	Research Site	Slaný
Hungary	Research Site	Baja
Hungary	Research Site	Debrecen
Hungary	Research Site	Kaposvar
Hungary	Research Site	Kecskemét
Hungary	Research Site	Pécs
Italy	Research Site	Pavia
Italy	Research Site	Vicenza
Poland	Research Site	Biala Podlaska
Poland	Research Site	Brodnica
Poland	Research Site	Lodz
Poland	Research Site	Pszczyna
Poland	Research Site	Sochaczew
Spain	Research Site #2	Barcelona
Spain	Research Site	Valencia
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Brookhaven	Mississippi
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chula Vista	California
United States	Research Site	Coral Gables	Florida
United States	Research Site	Denver	Colorado
United States	Research Site	Durham	North Carolina
United States	Research Site	El Paso	Texas
United States	Research Site	Granada Hills	California
United States	Research Site	Hampton	Virginia
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kinston	North Carolina
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Lynwood	California
United States	Research Site	McAllen	Texas
United States	Research Site	Middlebury	Connecticut
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Bern	North Carolina
United States	Research Site	Northridge	California
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Pontiac	Michigan
United States	Research Site	Roseville	Michigan
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Dimas	California
United States	Research Site	Tampa	Florida
United States	Research Site	Tupelo	Mississippi
United States	Research Site	Whittier	California
United States	Research Site	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Akebia Therapeutics	Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Hungary,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in hemoglobin (Hb) between Baseline (average pretreatment Hb) and the primary evaluation period (average Hb from Weeks 20 to 26, inclusive)		Baseline; Weeks 20 to 26
Secondary	Change in Hb value between Baseline and the secondary evaluation period (average Hb from Weeks 46 to 52)		Baseline; Weeks 46 to 52