Safety Profile and Clinical Outcomes in a Phase I, Placebo-Controlled Study of Siplizumab in Acute Graft-Versus-Host Disease

Background. Acute graft-versus-host disease (GVHD) is a major complication of both bone marrow and hematologic stem cell allografts. T cells and natural killer (NK) cells have been linked to the development of GVHD. Modulation of these cells via the CD2 receptor may be a potentially important approach to the management of this disease. Methods. The safety profile and tolerability of siplizumab (MEDI-507), a humanized anti-CD2 IgG-1 kappa monoclonal antibody, in the treatment of GVHD were evaluated in a phase I, double-blind, multiple-dose, placebo-controlled study. Thirty-four subjects with at least grade II acute GVHD were randomized to receive four doses of 0.012, 0.04, 0.12, or 0.4 mg/kg siplizumab or placebo intravenously every 3 days. Subjects received concurrent 2 mg/kg per day methylprednisolone for more than or equal to 10 days. Results. No meaningful difference occurred between siplizumab and placebo groups in the incidence or severity of adverse events or laboratory test results. No increase in incidence of infection secondary to siplizumab treatment was observed. During 100 days postinitial infusion, a modest increase in resolution of GVHD, grade 0 (67% vs. 54%, P=0.0629), was reported for the siplizumab-treated group. Conclusion. Siplizumab administered with corticosteroid therapy for grade II or higher acute GVHD treatment exhibited an acceptable safety profile that would support further clinical development.