TrialNet 09: Effects of CTLA-4 IG (Abatacept) on the Progression of Type 1 Diabetes in New Onset Subjects

The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. Therefore, this multicenter, double-blind, randomized, controlled trial evaluated the effect of abatacept in subjects with recently diagnosed type 1 diabetes mellitus. Subjects were randomly assigned in a 2:1 ratio to receive either the experimental treatment of 30 minute intravenous infusion of 10 mg/kg of CTLA-4 Ig (abatacept) or an intravenous saline solution (placebo). The treatments were administered on days 1, 14, 28, and then every 28 days for a total of 27 doses over 700 days. All subjects received intensive diabetes management with the goal of achieving excellent glycemic control. 2 hour mixed meal tolerance tests (MMTT) were performed at 3, 6, 12 and 18 months. Four hour MMTTs were performed at baseline and at 24 months. Safety and efficacy were assessed over a two year follow-up period.