A Study of Roxadustat to Treat Anemia in Children and Teenagers With Chronic Kidney Disease

Inclusion criteria

• Participant has a diagnosis of anemia in CKD Kidney Disease Outcomes Quality Initiative stages 3 or 4 or 5. This can include participants not on dialysis or dialysis dependent (DD) participants (including hemodialysis, peritoneal dialysis and hemodiafiltration participants).
• Participants not on dialysis must have an estimated glomerular filtration rate (Schwartz formula) of < 60 mL/min per 1.73 m^2.
• ESA-treated participants should have a screening Hb level, assessed via HemoCue, between 10.0 and 12.0 g/dL; ESA-naïve participants can have a Hb level ≤ 11 g/dL.
• Participant has a ferritin level > 100 ng/mL or a transferrin saturation (TSAT) value > 20%.
• Participant has an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) and total bilirubin (TBL) ≤ 1.5 x ULN at enrollment visit.
• Participant is treated with an ESA or is ESA-naïve, where ESA status is defined as:

• ESA-treated: Participant is taking a stable dose of an ESA for at least 4 weeks prior to screening.
• ESA-naïve: Participant has no prior ESA exposure OR participant's total prior ESA exposure ≤ 3 weeks within the preceding 4 weeks from screening OR participant was previously treated with and discontinued an ESA ≥ 8 weeks prior to screening.
• Female participant is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 4 weeks after final study intervention administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study and for 4 weeks post-last roxadustat dose.
• Female participant must not donate ova starting at first administration of roxadustat and throughout the study period and for 4 weeks post-last roxadustat dose.
• Male participants with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 4 weeks post-last roxadustat dose.
• Male participants must not donate sperm during the treatment period and for 4 weeks post-last roxadustat dose.
• Male participants with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 4 weeks post-last roxadustat dose.
• Participant and/or participant's parent or legal guardian agrees for the participant not to participate in another interventional study while participating in the present study.

Exclusion criteria

• Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
• Participant has any medical condition, including active, systemic or clinically significant infection which may pose a safety risk to a participant in this study, which may confound the safety or activity assessment or may interfere with study participation making the participant unsuitable for study.
• Participant has a known or suspected hypersensitivity to roxadustat, related hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI), or any components of the formulation used.
• Participant has uncontrolled hypertension (defined as ≥ 95th percentile + 12 mm Hg or ≥ 140/90 mm Hg [whichever is lower] for participants < 13 years of age and ≥ 140/90 mm Hg for participants ≥ 13 years of age measured 3 times at the same visit) in the 2 weeks prior to screening.
• Participant has a known hematologic disease other than anemia secondary to renal disease,(e.g., history of sickle cell disease, sickle cell anemia, hemoglobin sickle cell disease, or hemoglobin sickle cell beta thalassemia).
• Participant has untreated hypothyroidism.
• Participant has severe hyperparathyroidism defined as serum parathyroid hormone (PTH) levels above 1000 pg/mL intact PTH within 4 weeks of screening.
• Participant has a functioning kidney allograft.
• Participant has a folate or B12 or carnitine deficiency. Acceptable if treated to normal values within 4 weeks of screening.
• Participant has a known active malignancy or malignancy within 18 months before the screening visit. Radiation or chemotherapy must be completed at least 12 months before the screening visit.
• Participant has a scheduled living donor organ transplantation date within 12 weeks of screening. If participant becomes eligible for a kidney transplant during study conduct, the participant should be discontinued.
• Participant has a whole blood or packed red blood cells (pRBC) transfusion during the 8 weeks prior to screening.
• Participant has any current condition leading to active significant blood loss in the past 4 weeks.
• Participant has a diagnosis of hemolytic uremic syndrome within 12 weeks prior to screening.

• Participant who has a previous diagnosis of atypical hemolytic syndrome must be relapse-free (stable hemoglobin (Hb), normal platelet count, normal serum lactate dehydrogenase, and normal haptoglobin level) for more than 12 weeks prior to screening.
• Participant has a history of chronic liver disease, including comorbidity with autosomal recessive polycystic kidney disease, cystinosis, and primary hyperoxaluria.
• Participant had an episode of peritonitis within 30 days of screening.
• Participant has active inflammation such as glomerulonephritis flare (i.e., lupus nephritis, immunoglobulin A (IgA) nephritis, rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis, antineutrophil cytoplasmic antibodies vasculitis) requiring pulse corticosteroid treatment or induction treatment with an immunosuppressive agent (i.e., cyclophosphamide, rituximab, or another monoclonal antibody) within 6 weeks of screening visit. Receipt of monoclonal antibody or biologic for maintenance treatment of underlying condition is acceptable.
• Participant has a known history of human immunodeficiency virus infection.
• Participant has rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or is allergic to peanut or soya.