Study of Roxadustat in Non-Dialysis Chronic Kidney Disease Participants With Anemia

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Randomized, Open-Label, Dose Titration, Efficacy and Safety Study of FG-4592 (Roxadustat) in Non-Dialysis Chronic Kidney Disease Patients With Anemia

Conditions
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Chronic Kidney Disease, Anemia

Intervention / Treatment
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* Drug: Roxadustat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Roxadustat Tiered, Weight Based Dosing TIW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|
| Experimental: Cohort B: Roxadustat Tiered, Weight Based Dosing TIW then BIW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|
| Experimental: Cohort C: Roxadustat at 50 mg TIW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|
| Experimental: Cohort D: Roxadustat at 100 mg TIW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|
| Experimental: Cohort E: Roxadustat Tiered, Weight Based Dosing BIW then QW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|
| Experimental: Cohort F: Roxadustat at 70 mg BIW then QW<br>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. | Drug: Roxadustat<br>* Oral capsule<br>* Other names: FG-4592;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of Participants With an Hb Response by Week 17 | An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL. | Up to Week 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of Participants With an Hb Response by Weeks 5, 9, 13, 17, 21, and 25 | An Hb response was defined as a Hb level of ≥11 g/dL and an increase from BL ≥1 g/dL. | Up to Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) | 
| Change From Baseline in Hb at Weeks 5, 9, 13, 17, 21, and 25 | Baseline is defined as the mean of the last 3 available values predose. | Baseline, Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) | 
| 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 | 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. | 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) | 
| 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) | 
| 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 | Participants can have a Hb value for the same category (11-12, 11-13, or 10.5-13 g/dL) reported for multiple weeks. | Weeks 5, 9, 13, and 17 (all cohorts) and Weeks 21 and 25 (24-week treatment cohorts only) | 
| 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 Time to Hb Response: Hb Increase ≥1 g/dL From Baseline and Hb ≥11 g/dL | 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. | Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C-F) | 
| Median Initial Hb Responsive Time: Time to Initial Hb Increase ≥1.0 g/dL From Baseline | 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. | Up to Week 17 (Cohorts A and B) and up to Week 25 (Cohorts C, D, E, and F) | 
| 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) | 
| 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 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]) | 
| Mean of Weekly Hb Values <10.5, >13, and >14 g/dL During Weeks 13-17 and 18-25 | 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. | Weeks 13-17 (all cohorts) and 18-25 (24-week treatment cohorts only) | 
| Number (%) of Participants Requiring Rescue Therapy | 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 | Baseline up to Week 28 (end of study) | 
| Number (%) of Participants Requiring Therapeutic Phlebotomy |  | Baseline up to Week 28 (end of study) | 
| Number (%) of Participants Withdrawn From the Study Due to Inadequate Efficacy |  | Baseline up to Week 28 (end of study) | 
| Number (%) of Participants With Dose Changes During Weeks 1-4, 5-12, 13-16, and 17-24 | Dose changes include dose reductions, dose increases, and dose holds. | Weeks 1-4, 5-12, and 13-16 (all cohorts) and Weeks 17-24 (24-week treatment cohorts only) | 
| 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) | 
| 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 was defined as the mean of the last 3 available values predose. | Baseline, Weeks 16 (Cohorts A and B End of Treatment) and Week 24 (Cohorts C-F End of Treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, Kidney, Chronic Kidney Disease, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Erythropoietin, Blood count, Predialysis, Pre-dialysis, Hb, Non-dialysis