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Completed

NCT Number: NCT01147666

Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis

The primary objective of this study is to evaluate the efficacy and safety of roxadustat in participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, previously treated with intravenous (IV) epoetin alfa.

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Tempe, Arizona, United States

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About this study

Dose ranging study with consecutive cohorts in two participant populations: participants normally responding to current anemia treatment (epoetin alfa) ("normoresponders": participants with baseline epoetin alfa dose at study entry 75 to 450 international units [IU]/kilograms [kg]/week) and participants not responding well to current treatment ("hyporesponders": participants with maintenance epoetin alfa dose above 450 IU/kg/week). Normoresponders are randomized to study drug roxadustat or epoetin alfa at a ratio of 3:1; hyporesponders are randomized to study drug roxadustat or epoetin alfa or placebo at a ratio of 2:1:1. The study objectives are to demonstrate that roxadustat is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1
  • Two most recent Hb values obtained during screening period must be within the ranges set below:

i) Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL

  • Epoetin alfa, dose requirements:

i) Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (that is, no more than a 30% fluctuation in the weekly dose) during the 4 weeks prior to study Day -3

  • Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 85 IU/kg/dose, TIW; weekly dose between 75 and 255 IU/kg/week
  • Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 115 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week
  • Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week
  • Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between 75 and 345 IU/kg/week
  • Cohorts A-10 to A-12: Optional cohorts to be decided (TBD), dosing frequency and dose range to be determined by sponsor ii) Group B. Hyporesponder Criteria:

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  • Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week
  • Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range >115 IU/kg/dose, TIW; total weekly dose >345 IU/kg/week no requirement for stability of epoetin alfa doses
  • Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits
  • Absence of active or chronic gastrointestinal bleeding
  • High sensitivity C-reactive protein (hsCRP) <60 mg/liter for normoresponders Cohorts A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders
  • Body weight: 40 to 140 kg (dry weight)
  • Body mass index (BMI): 18 to 45 kg/meter square (m^2)
  • Dialysis vascular access via native arteriovenous fistula or synthetic graft, or permanent (tunneled) catheter (not via temporary catheter); permanent and temporary catheters, however, are still prohibited in Cohort A-5

Key Exclusion Criteria:

  • Anticipated change in HD prescription
  • Any clinically significant infection or evidence of an underlying infection
  • Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab)
  • History of chronic liver disease
  • New York Heart Association Class III or IV congestive heart failure
  • Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
  • History of myelodysplastic syndrome
  • History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
  • Active hemolysis or diagnosis of hemolytic syndrome
  • Known bone marrow fibrosis
  • Uncontrolled or symptomatic secondary hyperparathyroidism
  • Any prior organ transplantation
  • Drug-treated gastroparesis or short-bowel syndrome
  • History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the participant
  • Prior treatment with roxadustat
  • Diagnosis or suspicion of renal cell carcinoma
  • Red blood cell (RBC) transfusion within 12 weeks prior to Day 1, or anticipated need for RBC transfusion during the dosing period
  • IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron during the dosing/treatment period

Treatment and study plan

Roxadustat

Drug

Roxadustat will be administered per dose and schedule specified in the arms.

Other names: FG-4592

Epoetin alfa

Drug

Epoetin Alfa will be administered per dose and schedule specified in the arms.

Placebo

Other

Placebo matching to roxadustat will be administered per schedule specified in the arm.

Primary outcomes

  1. Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only

    Time frame: Week 7

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.

  2. Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks

    Time frame: Week 7

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

  3. Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks

    Time frame: Weeks 17, 18, 19, and 20

    The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

Secondary outcomes

  1. Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)

    Time frame: Weeks 17, 18, 19, and 20

    The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

  2. Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)

    Time frame: Weeks 17, 18, 19, and 20

    The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values.

  3. Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks

    Time frame: Baseline, Week 7

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

  4. Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks

    Time frame: Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

  5. Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only

    Time frame: Baseline up to Week 6

    Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

  6. Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks

    Time frame: Baseline up to Week 19

    Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

  7. Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks

    Time frame: Week 7

  8. Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks

    Time frame: Week 7

  9. Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level

    Time frame: Week 7

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

  10. Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level

    Time frame: Weeks 8, 10, 12, 14, 17, 19, and 20

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

  11. Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks

    Time frame: Baseline up to Week 6

    Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

  12. Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks

    Time frame: Baseline up to Week 19

    Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

  13. Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks

    Time frame: Baseline up to Week 6

  14. Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks

    Time frame: Baseline up to Week 19

  15. Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6

    Time frame: Baseline up to Week 6

    The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

  16. Trough Plasma Concentration of Roxadustat and Epoetin Alfa

    Time frame: Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6

Sponsors and collaborators

Lead sponsor

Kyntra Bio

Industry

Collaborators

  • Astellas Pharma Inc
  • AstraZeneca

Registry information

Official study title

A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) and Single-Blind Placebo-Controlled, Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Jun 22, 2010
Registry last updated
Jan 11, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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