Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis (Pyrenees)

Astellas

Status and phase: Completed; Phase 3

Conditions: Anemia; End Stage Renal Disease (ESRD)

Treatments: Drug: Iron; Drug: Roxadustat; Drug: Epoetin alfa; Drug: Darbepoetin alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT02278341

1517-CL-0613

2013-001497-16 (EudraCT Number)

Details and patient eligibility

About

This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.

Full description

This study consisted of three study periods as follows:

• Screening Period: up to 6 weeks
• Treatment Period: a minimum of 52 weeks up to a maximum of 104 weeks
• Follow-up Period: 4 weeks

Enrollment: 838 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Main Inclusion:

• Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization.
• Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization).
• Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period.
• 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

Exclusion criteria

Main Exclusion:

• Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization.
• Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD).
• Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
• Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization.
• Participant has a history of malignancy, except for 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.
• Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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838 participants in 2 patient groups

Roxadustat

Experimental group

Description:

Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.

Treatment:

Drug: Iron

Drug: Roxadustat

ESA (Erythropoiesis Stimulating Agent) treatment

Active Comparator group

Description:

Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from the epoetin alfa to darbepoetin alfa or vice versa.

Treatment:

Drug: Darbepoetin alfa

Drug: Epoetin alfa

Drug: Iron