Intervention: Roxadustat
Trial phase: Phase 2
ATC code: B03XA05
SMILES: Cc1nc(C(=O)NCC(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 10
Group description: Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.
Eligibility criteria:
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:
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