Study of Roxadustat Conversion in Participants Receiving Stable Erythropoiesis-Stimulating Agent (ESA) or as Initial Anemia Treatment in Chronic Dialysis Participants

A Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From a Continuous Erythropoietin Receptor Activator (CERA), or as Initial Anemia Treatment in Hemodialysis (HD) Patients - DENALI Study

The purpose of this study is to assess the safety and effectiveness of Roxadustat dosing regimens among chronic dialysis participants converted from ESA therapy or who are ESA-naïve.

Study Overview

• Status: Completed
• Conditions: Anemia Associated With End Stage Renal Disease (ESRD)
• Intervention / Treatment: Drug: Roxadustat

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Englewood, Colorado, United States, 80110
      • Investigational Site
  • Idaho
    • Caldwell, Idaho, United States, 83642
      • Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Investigational Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Investigational Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Investigational Site
  • Missouri
    • Saint Ann, Missouri, United States, 63074
      • Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Investigational Site
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Investigational Site
  • Utah
    • Saint George, Utah, United States, 84790
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Receiving chronic dialysis for end stage renal disease (ESRD)
• Vascular access must be a functioning native arteriovenous fistula or graft with adequate flow in the opinion of the investigator, or permanent tunneled catheter
• Screening hemoglobin criteria (based on central lab value; measured within 10 days prior to initiating Roxadustat treatment: Participants converting from CERA: screening heamoglobin was between 9.0 to 12.0 g/dL; Participants initiating anemia treatment: <10.0 g/dL
• Ferritin ≥ 50 nanograms (ng)/milliliter (mL), Transferrin saturation (TSAT) ≥ 10% at screening
• Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN at screening and prior to initiating roxadustat treatment.
• Body weight between 45.0 to 160.0 kg

Key Exclusion Criteria:

• Red blood cell (RBC) transfusion within 4 weeks prior to enrollment
• Known history of myelodysplastic syndrome or multiple myeloma
• Known hereditary hematologic disease or other known causes for anemia other than chronic kidney disease (CKD)
• Known chronic inflammatory disease that is determined by the investigator to be the primary cause of anemia
• Active or chronic gastrointestinal bleeding
• Treated with iron-chelating agents within 4 weeks prior to enrollment
• History of New York Heart Association (NYHA) Class III or IV congestive heart failure
• History of myocardial infarction (MI), acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (excluding vascular dialysis access stenosis/thrombosis) within 12 weeks prior to enrollment
• Uncontrolled hypertension, in the opinion of the Investigator
• Diagnosis or suspicion of renal cell carcinoma as shown on renal imaging performed within 24 weeks prior to enrollment
• History of malignancy, except for cancers determined to be cured or in remission for ≥2 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Roxadustat; Participants will receive roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant requires roxadustat <60 milligrams (mg)/week to maintain Hb levels, the dose frequency will be reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose will be based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with <6 weeks of prior CERA use, the initial roxadustat dose will be based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations will be made every 4 weeks and doses will be titrated based on Hb level and rate of Hb change. The prescribed dose will not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever is lower.

Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Hb Change From Baseline to Average Hb From Weeks 16-24	Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.	Baseline, Weeks 16-24
Percentage of Participants With Mean Hb Value ≥10 g/dL	Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.	Week 16 through Week 24

Collaborators and Investigators

• Sponsor: FibroGen
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 26, 2020
• Primary Completion (ACTUAL): June 30, 2021
• Study Completion (ACTUAL): October 11, 2021

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (ACTUAL): June 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Anemia
• Other Study ID Numbers: FGCL-4592-097

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