Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia
- Registration Number
- NCT01244763
- Lead Sponsor
- FibroGen
- Brief Summary
The primary purpose of this study is to evaluate efficacy and safety of roxadustat in the correction of anemia in participants with non-dialysis chronic kidney disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 145
Inclusion Criteria
- Age 18 to 75 years
- Chronic kidney disease, not receiving dialysis
- Body weight 45 to 140 kg
Exclusion Criteria
- 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
- Myocardial infarction or acute coronary syndrome within 12 weeks prior to randomization
- History of malignancy
- 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, multiple myeloma, or pure red cell aplasia
- History of hemosiderosis, hemochromatosis or polycystic kidney disease
- Active hemolysis or diagnosis of hemolytic syndrome
- Uncontrolled or symptomatic secondary hyperparathyroidism
- Seizure disorder or receiving anti-epilepsy medication
- Known bone marrow fibrosis
- Any prior or scheduled organ transplant
- Prior treatment with roxadustat or any hypoxia-inducible factor prolyl hydroxylase inhibitor
- History of alcohol or drug abuse
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Roxadustat Tiered, Weight Based Dosing TIW Roxadustat Participants will receive roxadustat capsules, administered orally 3 times weekly (TIW) for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kilograms (kg)\], medium-weight \[\>60 to 90 kg\], and heavy-weight \[\>90 to 140 kg\] participants will receive 60, 100, and 140 milligrams \[mg\] roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Cohort D: Roxadustat at 100 mg TIW Roxadustat Participants will receive roxadustat capsules at 100 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL. Cohort B: Roxadustat Tiered, Weight Based Dosing TIW then BIW Roxadustat Participants will receive roxadustat capsules orally for 16 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kg\], medium-weight \[\>60 to 90 kg\], and heavy-weight \[\>90 to 140 kg\] participants will receive 60, 100, and 140 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to 2 times a week (BIW) at the time of the initial Hb response. Cohort C: Roxadustat at 50 mg TIW Roxadustat Participants will receive roxadustat capsules at 50 mg, administered orally TIW for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.2 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 10.5-12 g/dL. Cohort E: Roxadustat Tiered, Weight Based Dosing BIW then QW Roxadustat Participants will receive roxadustat capsules for 24 weeks. Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low-weight \[45 to 60 kg\], medium-weight \[\>60 to 90 kg\], and heavy-weight \[\>90 to 140 kg\] participants will receive 70, 100, and 150 mg roxadustat, respectively). Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from BIW to 1 time a week (QW) at the time of the initial Hb response. Cohort F: Roxadustat at 70 mg BIW then QW Roxadustat Participants will receive roxadustat capsules at 70 mg for 24 weeks. Dose adjustments will be implemented (up to a maximum roxadustat dose of 2.5 mg/kg per dose) every 4 weeks starting Week 5 to maintain Hb levels at 11-13 g/dL. Participants will have a dose frequency reduction from TIW to BIW at the time of the initial Hb response. Then after \>8 weeks of stable Hb, dose frequency will be reduced from BIW to QW.
- Primary Outcome Measures
Name Time Method Number (%) of Participants With an Hb Response by Week 17 Up to Week 17 An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.
- Secondary Outcome Measures
Name Time Method Number (%) of Participants With an Hb Response by Weeks 5, 9, 13, 17, 21, and 25 Up to Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL.
Number (%) of Participants Requiring Therapeutic Phlebotomy Baseline up to Week 28 (end of study) Number (%) of Participants Who Achieve Maximum Hb Between 11-12, 11-13, and 10.5-13 g/dL by Weeks 5, 9, 13, 17, 21, and 25 Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) Participants can have a Hb value for the same category (11-12, 11-13, or 10.5-13 g/dL) reported for multiple weeks.
Number (%) of Participants With Maximum Hb <11, >12, >13, and >14 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28 Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only) Median Initial Hb Responsive Dose: Dose at Which Initial Hb Increases to ≥1.0 g/dL From Baseline Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C-F) Mean Hb Values From Participants Who Reached Hb >11.0 g/dL in the Hb 11-12, 11-13, and 10.5-13 g/dL Categories Cohorts A and B: Weekly through Week 16 (end of treatment [EoT]) and Week 20 (Follow up [4 weeks posttreatment]); Cohorts C-F: Weekly through Week 24 (EoT) and Week 28 (Follow up [4 weeks posttreatment]) Change From Baseline in Hb Stratified by Baseline Ferritin >100 Nanograms/Milliliter (ng/mL) and Transferrin Saturation >20% at Week 16 and Week 24 Baseline, Weeks 16 (Cohorts A and B End of Treatment) and Week 24 (Cohorts C-F End of Treatment) Baseline was defined as the mean of the last 3 available values predose.
Change From Baseline in Hb at Weeks 5, 9, 13, 17, 21, and 25 Baseline, Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) Baseline is defined as the mean of the last 3 available values predose.
Number (%) of Participants Withdrawn From the Study Due to Inadequate Efficacy Baseline up to Week 28 (end of study) Number (%) of Participants With Mean Hb Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 9-16, 13-16, 17-20, 17-24, 21-24, and 25-28 Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only) Participants can have a Hb value reported for more than 1 of the categories (11-12, 11-13, and 10.5-13 g/dL) during the week intervals since these categories are not mutually exclusive.
Number (%) of Participants With 2 Consecutive Hb Values Between 11-12, 11-13, and 10.5-13 g/dL During Weeks 5-8, 9-12, 13-16, 9-16, 17-20, 17-24, 21-24, and 25-28 Weeks 5-8, 9-12, 9-16, 13-16, and 17-20 (all cohorts) and Weeks 17-24, 21-24, and 25-28 (24-week treatment cohorts only) Median Time to Hb Response: Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C-F) Median time to response was estimated using Kaplan Meier method, Cohort A and B censored at Week 17, Cohort C, D, E, and F censored at Week 25. The median number of days presented was calculated from Baseline to the day the Hb response was achieved.
Change in Hb After Reaching a Hb Response of ≥11.0 g/dL and an Increase in Hb by ≥1.0 g/dL by Week Cohorts A and B: Weekly through Week 16 (end of treatment), Week 18 (2 weeks posttreatment), and Week 20 (4 weeks posttreatment); Cohorts C-F: Weekly through Week 24 (end of treatment), Week 26 (2 weeks posttreatment), and Week 28 (4 weeks posttreatment) Mean of Weekly Hb Values <10.5, >13, and >14 g/dL During Weeks 13-17 and 18-25 Weeks 13-17 (all cohorts) and 18-25 (24-week treatment cohorts only) The mean percentage of the scheduled weekly Hb values that were \<10.5, \>13, and \>14 g/dL during Weeks 13-17 and 18-25 is presented.
Median Initial Hb Responsive Time: Time to Initial Hb Increase ≥1.0 g/dL From Baseline Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C, D, E, and F) Median time to response was estimated using Kaplan Meier method; Cohort A and B censored at Week 17 and Cohort C, D, E, and F censored at Week 25. The median number of days presented was calculated from Baseline to the day the Hb response was achieved.
Number (%) of Participants Requiring Rescue Therapy Baseline up to Week 28 (end of study) Rescue treatment included recombinant erythropoiesis-stimulating agent (ESA), red blood cell transfusion (in the absence of a known bleeding episode or surgical blood loss), or intravenous (IV) Iron
Number (%) of Participants With Dose Changes During Weeks 1-4, 5-12, 13-16, and 17-24 Weeks 1-4, 5-12, and 13-16 (all cohorts) and Weeks 17-24 (24-week treatment cohorts only) Dose changes include dose reductions, dose increases, and dose holds.
Weekly Total Dose and Cumulative Total Dose (mg/kg) When First Achieving Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL) Cohorts A and B: Weekly through Week 16 (end of treatment); Cohorts C-F: Weekly through Week 24 (end of treatment) Mean Weekly Dose After Achieving First Hb Response (Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL) Cohorts A and B: Weekly through Week 16 (end of treatment); Cohorts C-F: Weekly through Week 24 (end of treatment)