Phase I clinical trial of a monoclonal antibody against CD40-Ligand (IDEC-131) in patients with systemic lupus erythematosus

Objective. To investigate the safety and pharmacology of a humanized monocl onal antibody against CD40-ligand (IDEC-131) in patients with systemic lupu s erythematosus (SLE). Methods. Cohorts of 3 to 5 patients with symptomatic lupus each received 0. 05, 0.25, 1.0, 5.0, or 15.0 mg/kg of IDEC-131 as a single intravenous infus ion. Patients were followed for 3 months to evaluate toxicity and pharmacok inetics. Results. This phase I, single dose, dose-escalating study was conducted in 23 patients at a single institution. All patients experienced at least 1 ad verse event (AE) during a 3 month followup period, although 58 AE in 17 pat ients were considered possibly or probably related or of unknown relationsh ip to treatment. No dose relationship in the distribution of AE was apparen t. No infusion related cytokine-release syndrome was observed; no infusions were interrupted, and all patients completed treatment. Eight mild (grade 1 or 2) infections were reported in 8 patients. All infections were conside red unrelated to drug administration and all resolved uneventfully. No pati ent developed detectable antibodies to IDEC-131. Flow cytometry revealed no apparent treatment related depletion of lymphocyte subsets. Pharmacokineti c analysis indicated that the maximum serum concentration and the area unde r the concentration curve of IDEC-131 were proportional to the dose adminis tered. At doses between 1.0 and 15.0 mg/kg, the serum half-life ranged from 299 to 320 h. Efficacy was not formally evaluated in this single dose stud y. Conclusion. IDEC-131 (humanized Mab against CD40L) administered in a single intravenous infusion at doses of 0.05-15.0 mg/kg is safe and well tolerate d in patients with SLE.