Study of Vadadustat in Hemodialysis Participants With Anemia Switching From Epoetin Alfa

NCT03799627 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AKB-6548-CI-0025
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 41

Brief Summary

This is a Phase 2 open-label efficacy, safety, and pharmacokinetic/pharmacodynamic (PK/PD) study to evaluate oral Vadadustat for the treatment of anemia in hemodialysis participants converting from Epoetin Alfa therapy.

Conditions

Anemia; Dialysis-dependent Chronic Kidney Disease

Keywords

Vadadustat; AKB-6548; Anemia; Chronic kidney disease (CKD); erythropoietin

Outcome Measures

Primary Outcomes (5)

• Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP)

  Change from Baseline in Hb value was calculated as the PEP Hb value minus the Baseline Hb value. The PEP value was the average Hb value from Week 10 to Week 12. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1.

  Baseline; Week 10 to Week 12

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. TEAEs, defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, are reported.

  Up to Week 24

• Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

  Parameters assessed for laboratory values included hematology (excluding the primary and secondary efficacy endpoint results related to Hb), clinical chemistry, lipid profiles, and glucose. The investigator was responsible for reviewing laboratory results for clinically significant changes.

  Up to Week 24

• Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values

  Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing vital sign values for clinically significant changes.

  Up to Week 24

• Number of Participants Classified as Hb Outliers

  The target range for Hb was from 10.0 to 11.0 grams per deciliter (g/dL). Hb outliers included participants with a Hb increase of more than 12.0 g/dL or \<8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline, and a Hb increase to more than 1.0 g/dL within any 2-week interval during the Study Period.

  Weeks 13 - 20

Secondary Outcomes (23)

• Number of Participants With Hb Values Within the Target Range at the PEP

  Week 10 to Week 12

• Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12

  Week 10 to Week 12; Week 18 to Week 20

• Mean Change in Hb Between Baseline and the SEP

  Baseline; Week 18 to Week 20

• Number of Participants With Hb Values Within the Target Range at the SEP

  Week 18 to Week 20

• Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing

  Week 18 to Week 20

Study Arms (3)

Vadadustat

EXPERIMENTAL

The initial dose of Vadadustat (300, 450, or 600 milligrams \[mg\]) will be based upon the dose of Epoetin Alfa dose participants had received prior to Vadadustat treatment

Drug: Vadadustat

Vadadustat TIW

EXPERIMENTAL

Participants randomized to Vadadustat (Main and erythropoiesis-stimulating agent \[ESA\] hyporesponder parallel studies) who complete a once-daily dosing regimen treatment period and meet eligibility criteria for transition to three times weekly (TIW) dosing will switch to TIW dosing

Drug: Vadadustat TIW

Epoetin Alfa

ACTIVE COMPARATOR

Epoetin Alfa

Drug: Epoetin Alfa

Interventions

Vadadustat DRUG

Vadadustat Tablets 150 mg

Also known as: AKB-6548

Vadadustat

Epoetin Alfa DRUG

Epoetin Alfa

Also known as: Procrit, Epogen

Epoetin Alfa

Vadadustat TIW DRUG

Oral Vadadustat

Vadadustat TIW

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age, providing informed consent
• Receiving chronic, outpatient in-center hemodialysis (TIW) for end-stage renal disease for at least 12 weeks prior to Screening
• Maintained on intravenous Epoetin Alfa therapy for 8 weeks prior to and including Screening through Screening Visit 2 (SV2)
• Eligibility in the Main study and erythropoiesis-stimulating agent (ESA) hyporesponder parallel study is based on the following mean weekly Epoetin Alfa doses:
• Main study: Mean weekly Epoetin Alfa dose \<300 Units per kilogram per week (U/kg/week) for 8 weeks prior to SV2;
• ESA hyporesponder parallel study: Mean weekly Epoetin Alfa dose ≥300 U/kg/week for 8 weeks prior to SV2
• Two Hb values measured by the central laboratory at least 4 days apart between Screening Visit 1 (SV1) and SV2 as indicated:.
• Main study: 2 Hb values between 8.5 and 11.0 g/dL, inclusive;
• ESA hyporesponder parallel study: 2 Hb values between 8.0 and 10.0 grams per deciliter (g/dL), inclusive
• 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
• 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
• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

You may not qualify if:

• 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)
• Active bleeding or recent blood loss within 8 weeks prior to randomization
• Red blood cell (RBC) transfusion within 8 weeks prior to randomization
• Anticipated to discontinue hemodialysis during the study
• Judged by the Investigator that the participant is likely to need rescue therapy (ESA administration or RBC transfusion) immediately after enrollment in the study
• 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 (ULN) 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 Epoetin Alfa
• 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 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 participants 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)

Sponsors & Collaborators

• Akebia Therapeutics: lead

Study Sites (41)

Research Site

Fresno, California, 93720, United States

Location

Research Site

Granada Hills, California, 91344, United States

Location

Research Site

Los Angeles, California, 90022, United States

Location

Research Site

Northridge, California, 91324, United States

Location

Research Site

Riverside, California, 92501, United States

Location

Research Site #1

San Dimas, California, 91773, United States

Location

Research Site #2

San Dimas, California, 91773, United States

Location

Research Site

San Gabriel, California, 91776, United States

Location

Research Site

Tarzana, California, 91356, United States

Location

Research Site

Vacaville, California, 95688, United States

Location

Research Site

Victorville, California, 92394, United States

Location

Research Site

Denver, Colorado, 80230, United States

Location

Research Site

Bridgeport, Connecticut, 06606, United States

Location

Research Site

Hartford, Connecticut, 06762, United States

Location

Research Site

Coral Gables, Florida, 33134, United States

Location

Research Site

Hollywood, Florida, 33024, United States

Location

Research Site

Miami, Florida, 33126, United States

Location

Research Site

Miami, Florida, 33134, United States

Location

Research Site

Miami, Florida, 33150, United States

Location

Research Site

Tampa, Florida, 33607, United States

Location

Research Site

Tampa, Florida, 33614, United States

Location

Research Site

Winter Park, Florida, 32789, United States

Location

Research Site

Augusta, Georgia, 30909, United States

Location

Research Site

Statesboro, Georgia, 30458, United States

Location

Research Site

Roseville, Michigan, 48066, United States

Location

Research Site #1

Minneapolis, Minnesota, 55404, United States

Location

Research Site #2

Minneapolis, Minnesota, 55404, United States

Location

Research Site

Kansas City, Missouri, 64111, United States

Location

Research Site

Las Vegas, Nevada, 89107, United States

Location

Research Site

The Bronx, New York, 10461, United States

Location

Research Site

Asheville, North Carolina, 28801, United States

Location

Research Site

Wilmington, North Carolina, 28401, United States

Location

Research Site

Canton, Ohio, 44718, United States

Location

Research Site

Oklahoma City, Oklahoma, 73116, United States

Location

Research Site

El Paso, Texas, 79915, United States

Location

Research Site

Houston, Texas, 77004, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

San Antonio, Texas, 78258, United States

Location

Research Site

Chesapeake, Virginia, 23320, United States

Location

Research Site

Norfolk, Virginia, 23510, United States

Location

Research Site

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 36005278 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

vadadustat; Epoetin Alfa

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Conclusions were drawn from results of the Main Study (n=165). As the sample size in the Erythropoiesis-stimulating Agent (ESA) Hyporesponder Parallel Study (n=10) was small in both the Vadadustat and Epoetin Alfa treatment groups, these results did not allow to meaningful interpretation of the data.

Results Point of Contact

• Title: Akebia Therapeutics, Inc
• Organization: Akebia Therapeutics, Inc

trials@akebia.com

617-844-6128

Study Officials

• Chief Medical Officer

  Akebia Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Open-Label, Active-Controlled

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: January 10, 2019
• Study Start: January 31, 2019
• Primary Completion: June 5, 2020
• Study Completion: July 15, 2020
• Last Updated: September 29, 2022
• Results First Posted: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (41)