Study of Roxadustat (FG-4592) to Correct Anemia in Newly Initiated Dialysis Participants Not on Erythropoiesis-Stimulating Agent Treatment

A Phase 2, Randomized, Open-Label, Dose Titration, Safety and Efficacy Study of FG-4592 for the Correction of Anemia in Newly Initiated Dialysis Patients Not on Erythropoiesis-Stimulating Agent Treatment

The purpose of this study is to evaluate efficacy and safety of roxadustat in the correction of anemia in participants with end-stage renal disease who recently started dialysis.

Participants on hemodialysis (HD) will be randomized to 3 treatment arms (A, B, and C) of in a 1:1:1 ratio to receive no iron supplementation, oral iron supplementation, and IV iron supplementation, respectively, in addition to roxadustat. At the same time, participants on peritoneal dialysis (PD) will be enrolled into Arm D. Arm E will enroll either HD or PD participants, and is an optional, confirmatory/supplemental treatment arm with flexible dosing and flexible iron supplementation based on the evaluation of data from the previous 4 treatment arms.

Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight [40 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 140, 200, and 300 mg for low, medium, and high weight participants, respectively) during Weeks 5 and 9, depending on the hemoglobin (Hb) level and rate of Hb rise in the previous 4 weeks.

Inclusion Criteria:

• Receiving HD or PD for native kidney end-stage renal disease (ESRD) for 2 weeks to 4 months, prior to randomization
• Mean of the 2 most recent Hb values during the screening period, obtained at least 7 days apart, must be <10.0 grams (g)/deciliter (dL), with a difference of ≤1.0 g/dL between the 2 values
• Body weight 40 to 140 kilograms (kg)

Exclusion Criteria:

• Previously received erythropoiesis-stimulating agents
• Received IV iron within 4 weeks of randomization
• Received red blood cell transfusion within 8 weeks prior to randomization or anticipated need for transfusion during the treatment period
• 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
• Clinically significant infection
• New York Heart Association Class III or IV congestive heart failure
• History of malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps
• 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 other blood disorders
• Active hemolysis or diagnosis of hemolytic syndrome
• Known bone marrow fibrosis
• Uncontrolled or symptomatic secondary hyperparathyroidism
• History of alcohol or drug abuse within a year prior to randomization, or anticipated inability to avoid consumption of more than 3 alcoholic beverages per day
• History of allergy or sensitivity to oral or IV iron therapy
• Seizure disorder or receiving anti-epilepsy medication for seizure disorder within 12 weeks prior to randomization
• Pregnant or breast-feeding females