Study of Roxadustat Conversion in Participants Receiving Stable ESA or as Initial Anemia Treatment in Hemodialysis Participants

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and effectiveness of roxadustat dosing regimens among hemodialysis participants converted from erythropoiesis stimulating agent (ESA) therapy or who are ESA-naïve.

Official Title
-----------------
Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From an Erythropoiesis Stimulating Agent (ESA), or as Initial Anemia Treatment in Hemodialysis (HD) Patients

Conditions
-----------------
Anemia Associated With End Stage Renal Disease

Intervention / Treatment
-----------------
* Drug: Roxadustat


Participation Criteria
=================
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 tunnelled catheter Screening Hb criteria: Participants converting from an ESA: between 9.0 to 12.0 grams (g)/deciliter (dL); Participants initiating anemia treatment: < 10.0 g/dL Ferritin ≥ 50 nanograms (ng)/mililiter (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, 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 Participant has a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma (Principal Investigator's discretion) 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roxadustat<br>Participants will receive roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant require roxadustat <60 milligrams (mg)/week to maintain hemoglobin (Hb) levels, the dose frequency will be reduced in a stepwise manner, for example, to twice weekly (BIW), and then once weekly (QW). For participants converted from an ESA, the initial roxadustat dose will be based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for methoxy polyethylene glycol-epoetin beta [Mircera®]). For participants with <6 weeks of prior ESA 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. | Drug: Roxadustat<br>* Roxadustat will be administered per dose and schedule specified in the arm description.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. 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. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution. | Week 16 through Week 24 | 
| 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. | Baseline, Weeks 16-24 |