A dose exploration, phase I/II study of administration of continuous erythropoietin receptor activator once every 3 weeks in anemic patients with multiple myeloma receiving chemotherapy.

Background And Objectives: Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life, which has the potential for administration at extended dosing intervals. The objectives of this dose-finding study were to evaluate the hemoglobin (Hb) dose-response, pharmacokinetics, and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma (MM) receiving chemotherapy.

Design And Methods: This was an exploratory two-stage, open-label, parallel-group, multicenter study. Patients received C.E.R.A. doses of 1.0, 2.0, 3.5, 4.2, 5.0, 6.5, or 8.0 mg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks, followed by a 12-week optional extension period. The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period, based on values of the slope of the linear regression analysis and the area under the curve. Rates of Hb response (defined as an increase in Hb of > or =2 g/dL without transfusion) and blood transfusion were also evaluated.

Results: Sixty-four patients entered the study. Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0-4.2 mg/kg, with a similar response observed at higher doses. At least 70% of patients receiving 2.0-8.0 mg/kg of C.E.R.A. had Hb responses during the 18-week study. The elimination half-life of C.E.R.A. was found to be long (6.3-9.7 days [151.2-232.8 hours]). All doses were generally well tolerated.

Interpretation And Conclusions: Based on its unique, long elimination half-life, C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy.