Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Participants With Chronic Kidney Disease

Study Overview
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Brief Summary
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This is a randomized, open-label, multi-center study in dialysis chronic kidney disease (CKD) participants to evaluate the efficacy and relative safety of different dosing regimens of roxadustat over a 36-week treatment period. There are 3 study periods: Screening Period (up to 4 weeks) Treatment Period (36 weeks) Part 1: Correction/Conversion Period (Weeks 1-20) Part 2: Hemoglobin (Hb) Maintenance Period (Weeks 21-36) Follow-up Period (4 weeks)

Detailed Description
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Approximately 102 erythropoiesis stimulating agents (ESA)-naïve participants and 204 ESA-treated participants will be enrolled and randomized respectively in a 1:1 ratio to receive roxadustat at one of 2 starting doses as below: Low weight-based dosing: 70 milligrams (mg) 3 times a week (TIW) for body weight <60 kilograms (kg) or 100 mg TIW for body weight ≥60 kg Standard weight-based dosing: 100 mg TIW for body weight <60 kg or 120 mg TIW for body weight ≥60 kg After 20 weeks of treatment, all eligible participants whose last 2 Hb levels ≥105 grams (g)/liter (L) and change in Hb over the most recent 4 weeks is > - 10 g/L will switch to receive roxadustat for another 16 weeks to evaluate the efficacy and safety of new dosing regimens. At the end of Week 36, all participants will discontinue roxadustat and enter a 4-week Follow-up Period.

Official Title
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A Prospective, Randomized, Open-Label, Multi-Center Study to Evaluate the Efficacy and Safety of Multiple Roxadustat Dosing Regimens for the Treatment of Anemia in Dialysis Subjects With Chronic Kidney Disease

Conditions
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CKD Anemia in Dialysis Participants

Intervention / Treatment
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* Drug: Roxadustat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. CKD with end-stage renal disease (ESRD) on either hemodialysis (HD) or peritoneal dialysis (PD) Exclusion Criteria: Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab). Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event (for example, deep venous thrombosis or pulmonary embolism) within 26 weeks prior to Day 1. History of malignancy, myelodysplastic syndrome, and multiple myeloma. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (for example, systemic lupus erythematosis [SLE], rheumatoid arthritis, celiac disease). Clinically significant gastrointestinal bleeding. Women of childbearing potential and men with sexual partners of child bearing potential who are not using adequate contraception.

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: Part 1: ESA-Naïve Participants - Low Weight Based Dosing<br>ESA-naïve participants will receive roxadustat 70 mg TIW for body weight 45 to <60 kg or 100 mg TIW for body weight ≥60 kg. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 1: ESA-Naïve Participants - Standard Weight Based Dosing<br>ESA naïve participants will receive roxadustat 100 mg TIW for body weight 45 to <60 kg or 120 mg TIW for body weight ≥60 kg. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 1: ESA-Treated Participants - Low Weight Based Dosing<br>ESA-treated participants will receive roxadustat 70 mg TIW for body weight 45 to <60 kg or 100 mg TIW for body weight ≥60 kg. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 1: ESA-Treated Participants - Standard Weight Based Dosing<br>ESA treated participants will receive roxadustat 100 mg TIW for body weight 45 to <60 kg or 120 mg TIW for body weight ≥60 kg. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 2: Roxadustat QW<br>Participants will receive roxadustat once a week (QW). Roxadustat dose will be 2-dose step increase from originally planned week 21 TIW per dose amount. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 2: Roxadustat BIW<br>Participants will receive roxadustat twice a week (BIW). Roxadustat dose will be 1-dose step increase from originally planned week 21 TIW per dose amount. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Experimental: Part 2: Roxadustat TIW<br>Participants will receive roxadustat TIW. Roxadustat dose will continue per dose adjustment guideline. | Drug: Roxadustat<br>* Roxadustat will be dosed orally per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 (ESA Naïve): Percentage of Participants who Achieved Hb ≥110 g/L in the First 20 Weeks |  | Weeks 1 to 20 | 
| Part 1 (ESA Treated): Percentage of Participants who Achieved Mean Hb ≥100 g/L Averaged Over Weeks 17 to 21 Visits |  | Weeks 17 to 21 | 
| Part 2: Mean Hb Value Averaged Over Weeks 33 to 37 Visits |  | Weeks 33 to 37 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Mean Change in Hb Level From Baseline to Average Over Weeks 17 to 21 Visits |  | Baseline, Weeks 17 to 21 | 
| Part 1 (ESA-Naïve): Percentage of Participants With Mean Hb (Averaged Weeks 17 to 21 Visits) ≥100 g/L |  | Weeks 17 to 21 | 
| Part 2: Percentage of Participants With Mean Hb (Averaged Weeks 33 to 37 Visits) ≥100 g/L |  | Weeks 33 to 37 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemoglobin, Anemia, Chronic Kidney Disease Dialysis, End stage renal disease