A PHASE I/II MULTIPLE DOSE STUDY OF HuM291, A HUMANIZED ANTI-CD3 MONOCLONAL ANTIBODY, IN PATIENTS EXPERIENCING RENAL ALLOGRAFT REJECTION

Abstract

626 HuM291 is a humanized anti-CD3 monoclonal antibody which has been engineered to be less activating than the murine anti-CD3 antibody currently available. Data from a single dose phase I study in ESRD patients showed that treatment with a single dose of HuM291 resulted in profound, yet reversible T cell depletion. Symptoms of cytokine release were mild to moderate and limited to 24 hours post dosing. No human antibody production to HuM291 was detected. The present study was designed to determine the dose and dosing interval of HuM291 necessary to achieve up to 14 days of profound T cell depletion. Renal transplant patients who were experiencing a mild to moderate acute rejection episode were treated with 3 doses of HuM291 in addition to corticosteroids for the treatment of rejection. Dosing began at 0.0015 mg/kg q2d. Both the dose level and dose interval were increased based on the CD3 counts following treatment. To date, 7 patients have been entered in the study at 3 dose levels (0.0015 mg/kg, 0.0045 mg/kg, and 0.015 mg/kg) all at the q 2d dosing interval. T cell depletion was observed at all dose levels, but the degree and duration of depletion increased with increasing the dose. To date, no symptoms of cytokine release have been observed and no serious adverse events have been reported. A total of 30 patients will be entered into this study. In the two Phase 1 studies conducted thus far, HuM291 appears to be a very promising drug to bring forward into Phase II efficacy trials.