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

Primary Purpose

Anemia Associated With End Stage Renal Disease (ESRD)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Roxadustat
Sponsored by
FibroGen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia Associated With End Stage Renal Disease (ESRD)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Roxadustat

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 27, 2020
Last Updated
August 19, 2022
Sponsor
FibroGen
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04410198
Brief Title
Study of Roxadustat Conversion in Participants Receiving Stable Erythropoiesis-Stimulating Agent (ESA) or as Initial Anemia Treatment in Chronic Dialysis Participants
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
May 26, 2020 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
October 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FibroGen
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia Associated With End Stage Renal Disease (ESRD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
203 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Roxadustat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Roxadustat
Intervention Description
Roxadustat will be administered per dose and schedule specified in the arm description.
Primary Outcome Measure Information:
Title
Percentage of Participants With Mean Hb Value ≥10 g/dL
Description
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.
Time Frame
Week 16 through Week 24
Title
Mean Hb Change From Baseline to Average Hb From Weeks 16-24
Description
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.
Time Frame
Baseline, Weeks 16-24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Eisner
Organizational Affiliation
FibroGen
Official's Role
Study Chair
Facility Information:
Facility Name
Investigational Site
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
Facility Name
Investigational Site
City
Caldwell
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Investigational Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Investigational Site
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49009
Country
United States
Facility Name
Investigational Site
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Investigational Site
City
Saint Ann
State/Province
Missouri
ZIP/Postal Code
63074
Country
United States
Facility Name
Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Investigational Site
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77479
Country
United States
Facility Name
Investigational Site
City
Saint George
State/Province
Utah
ZIP/Postal Code
84790
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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