A Study of Roxadustat for the Treatment of Anemia in Participants With Chronic Kidney Disease and Not Receiving Dialysis

FibroGen

Status and phase: Completed; Phase 3

Conditions: CKD Anemia

Treatments: Drug: Placebo; Drug: Roxadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01750190

FGCL-4592-060

Details and patient eligibility

About

The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants with chronic kidney disease and not on dialysis.

Full description

There is a screening period of up to 6 weeks, a variable treatment period for individual participants. In order to complete the treatment period simultaneously for all study participants, the minimum treatment duration may be less than 52 weeks, with a maximum treatment duration of up to 3 years after the last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants who prematurely discontinued from treatment will be expected to complete the Early Termination (ET) and End of Study (EOS) visits. Such participants will be considered non-completers, but they will be expected to participate in long-term follow-up (LTFU) for cardiovascular events (CV) of interest, vital status, and hospitalizations until overall study closure unless the participant withdrew consent for this LTFU data collection. Participants were randomized in a 2:1 ratio to receive either roxadustat or placebo in a double-blind manner.

Enrollment: 922 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic kidney disease Stages 3, 4, or 5 and not receiving dialysis
• Anemia qualified by measurements of hemoglobin values during screening
• Additional blood work must be in a safe range for study entry
• Body weight 45 to 160 kilograms (kg)
• Willingness to use contraception if of child-bearing potential

Exclusion criteria

• Treatment with an erythropoiesis-stimulating agent (ESA) within 12 weeks prior to study participation
• More than 1 dose of intravenous iron within 12 weeks prior to study participation
• Blood transfusion within 8 weeks prior to study participation
• Active infection
• Chronic liver disease
• Severe congestive heart failure, recent heart attack, stroke, seizure, or blood clot
• Uncontrolled blood pressure within 2 weeks prior to study participation
• Renal cell carcinoma
• History of malignancy, including multiple myeloma or other myelodysplastic syndrome
• Chronic inflammatory disease that could impact red blood cell production
• Any prior organ transplant or a scheduled organ transplantation
• Anticipated elective surgery that is expected to lead to significant blood loss or anticipated elective heart procedure
• Gastrointestinal bleeding
• Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
• Recent use of an investigational drug or treatment, or participation in an investigational study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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922 participants in 2 patient groups, including a placebo group

Roxadustat

Experimental group

Description:

Participants will receive roxadustat tablets orally 3 times a week (TIW). The initial dose will be according to the tiered weight-based approach, with starting roxadustat doses of 70 milligrams (mg) TIW to participants weighing \<70 kilograms (kg) and roxadustat doses of 100 mg TIW to participants weighing ≥70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of ≥11.0 grams/deciliter (g/dL) and Hb increase from baseline (BL) of ≥1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 234.9 weeks.

Treatment:

Drug: Roxadustat

Placebo

Placebo Comparator group

Description:

Participants will receive roxadustat-matching placebo tablets orally TIW. The initial dose will be according to the tiered weight-based approach, with starting roxadustat-matching placebo doses of 70 mg TIW to participants weighing \<70 kg and roxadustat-matching placebo doses of 100 mg TIW to participants weighing ≥70 kg. Dose-titration (up to a maximum dose of 300 mg) will be performed based upon regular measurement of Hb levels until the participant achieves central Hb value of ≥11.0 g/dL and Hb increase from BL of ≥1.0 g/dL at 2 consecutive study visits, separated by at least 5 days. Once target Hb level is reached, the participant will enter the maintenance period during which roxadustat dosage will be adjusted every 4 weeks to maintain participant's Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The maximum treatment duration will be up to 208.1 weeks.

Treatment:

Drug: Placebo