TYPE 1 DIABETES TRIALNET PROTOCOL TN-05 / EFFECTS OF RITUXIMAB ON THE PROGRESS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The study is a two-arm, multicenter, randomized, double masked, placebo-controlled clinical trial to assess the safety, efficacy, and mode of action of rituximab, anti-CD20 monoclonal antibody, for the treatment of individuals with new onset type 1 diabetes. Subjects in both arms will receive standard intensive diabetes treatment with insulin and dietary management. Rituximab (RITUXANR, Genetech and Biogen Idec) is a chimeric murine/human monoclonal antibody approved for the treatment of B cell non-Hodgkin's lymphoma. The antibody binds to the CD20 antigen on the surface of B cells and mediates B cell depletion. Participants randomly assigned to rituximab treatment will receive four doses of 375mg/m2 IV each a week apart. Total study duration is approximately 4 years (2 years subject accrual and 2 years follow-up per subject). Follow-up for up to 4 years will continue for those who have persistence of beta cell function at 2 years and/or detectable immunologic effects of treatment by descriptive analysis until the disappearance of detectable beta cell function or resolution of immunologic changes. The primary statistical hypothesis to be assessed in this study is whether the mean C-peptide value for study subjects on rituximab differs significantly from the mean value for placebo subjects assessed at one year of follow-up. Secondary Goals The study will examine the effect of the proposed treatment on surrogate markers for immunologic effects, namely disease-specific outcomes and immunological outcomes. Major inclusion criteria are: Type 1 diabetes within past 3 months, age 8-45 years, and at least one diabetes associated autoantibody.