Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis

FibroGen

Status and phase: Completed; Phase 3

Conditions: CKD Anemia in Stable Dialysis Patients

Treatments: Drug: Roxadustat; Drug: Epoetin Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT02273726

FGCL-4592-064

Details and patient eligibility

About

The primary objective of this study is to evaluate the efficacy and safety of roxadustat compared with active control (epoetin alfa) for the maintenance treatment of anemia in participants with ESRD on dialysis.

Full description

This study will consist of three study periods as follows:

1. Screening Period of up to 6 weeks (8 weeks if on Mircera)
2. Treatment Period: a minimum of 52 weeks, a maximum of up to 3 years from the date last participant is randomized. Minimum study duration for participants enrolled under Protocol Amendment 1 or 2 may be less than 52 weeks
3. A Follow-up period of 4 weeks.

Participants will be randomized in a 1:1 ratio to receive either roxadustat or epoetin alfa (active control) in an open-label manner.

Enrollment: 741 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Receiving dialysis for ESRD for ≥3 months. Incident dialysis participants (under Amendment 1 and 2) receiving dialysis for ESRD for ≥ 2 weeks but ≤ 4 months at the time of randomization
• Participants must be on ESA for ≥ 8 weeks prior to screening; incident dialysis participants must be on ESA for ≥ 4 weeks prior to screening.
• Mean of the 3 most recent central lab Hb values during the Screening Period must be ≥ 9.0 g/dL and ≤ 12.0 g/dL (for incident dialysis participants, mean of the 2 most recent Hb values must be ≥ 8.5 g/dL and ≤ 12.0 g/dL); with an absolute difference of ≤ 1.3 g/dL between the highest and the lowest value. Samples are obtained at least 4 days apart (2 days under Amendment 2) and the last Hb value must be within 10 days prior to the randomization visit
• Participants with ferritin level ≥ 100 nanograms (ng)/milliliter (mL) (<100 ng/mL under Amendment 2) or transferrin saturation (TSAT) ≥ 20% (<20% under Amendment 2) at screening may qualify upon receiving iron supplement (per local standard of care)
• Participants with a serum folate and Vitamin B12 ≥ lower limit of normal (LLN) (< LLN under Amendment 2) at screening may qualify upon receiving supplement (per local standard of care)
• Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3x the upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5x ULN at screening
• Participant's body weight is 45 kilograms (kg) to 160 kg.

Exclusion criteria

• Participant has received an red blood cell (RBC) transfusion within 8 weeks (4 weeks under Amendment 2) prior to randomization
• Participant has known history of myelodysplastic syndrome or multiple myeloma
• Participant has known inherited disease such as thalassemia or sickle cell anemia or other known causes for anemia other than chronic kidney disease.
• Participant has known hemosiderosis, hemochromatosis, coagulation disorder,or hypercoagulable condition
• Participant has known chronic inflammatory disease that could cause anemia
• Participant has anticipated surgery that is expected to cause blood loss
• Participant has known gastrointestinal bleeding
• Participant has history of chronic liver disease (for example, chronic infectious hepatitis,chronic auto-immune liver disease,cirrhosis, or fibrosis of the liver)
• Participant with New York Heart Association (NYHA) Class III or IV congestive heart failure
• Participant has had a heart attack, stroke, seizure, or a thrombotic/thromboembolic event (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to participating in the study
• Participant has uncontrolled high blood pressure within 2 weeks prior to participating in the study
• Participant has a history of malignancy, except for the following: 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.)
• Participant is positive for human immunodeficiency virus (HIV), Hepatitis B surface antigen, or anti-hepatitis C virus antibody
• Participant with prior organ transplant who experience rejection within 6 months or on high doses of immunosuppressive therapy
• Participant has any of the following known untreated conditions; proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

741 participants in 2 patient groups

Roxadustat

Experimental group

Description:

Participants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on the participant's average prescribed erythropoietin stimulating agent (ESA) dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments will be permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose is 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever is lower).

Treatment:

Drug: Roxadustat

Epoetin Alfa

Active Comparator group

Description:

Participants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose will be based on the participant's average weekly prescribed ESA dose in 4 weeks prior to randomization if on epoetin or darbepoetin, and average monthly (4-week) prescribed ESA dose in 8 weeks prior to randomization if on Mircera®. In case of a change in route of administration from SC to IV (TIW), the initial dose of IV epoetin alfa will be determined by the investigator per local standard of care (SOC). Dose adjustments will follow the recommendations as per the approved country-specific product label (United States Package Insert \[USPI\] or Summary of Product Characteristics \[SmPC\]) or local SOC.

Treatment:

Drug: Epoetin Alfa