Data from three ITN type 1 diabetes trials will be featured during the “Clinical Trials of T Cell Therapeutics for Reversing Type 1 Diabetes” session at the Annual American Diabetes Association (ADA) Scientific Sessions in Chicago, IL. This session will take place on June 22 from 8:00am-10:00am CT.
Type 1 diabetes (T1D) results from T cell mediated destruction of insulin-producing beta cells, and prior preclinical and clinical studies show that therapies targeting T cells can preserve beta cell function. As such, the ITN has initiated a number of clinical trials with T cell targeting immune modulators to potentially establish tolerance.
Steve Gitelman, MD (University of California, San Francisco) will present data from the START study, “Study of Thymoglobulin to Arrest Type 1 Diabetes.” The goal of the START study is to determine whether rabbit polyclonal anti-thymocyte globulin (ATG) can induce tolerance and thereby prolong endogenous insulin secretion in new onset T1D. Dr. Gitelman’s talk will report on the results of this phase II clinical trial of the safety and efficacy of ATG in recent-onset T1D.
ATG has been chosen as a potential T cell-targeting therapy for this study because it not only depletes lymphocytes, but also acts at other levels, including modulation of T cell activation, homing, and cytotoxic activities, induction of regulatory T cells, and may also affect antigen-presenting cells. ATG has also exhibited promising results in prior research: several doses can induce a lasting remission in the NOD mouse, and several smaller pilot clinical studies with ATG alone or in combination with other drugs preserve endogenous insulin secretion.
Mark Rigby, MD (Indiana University) will present data from the T1DAL study, “Inducing Remission in new Onset T1DM with Alefacept (Amevive®). Alefacept is a fusion protein that blocks immune activation by interrupting the the interaction between the CD2 receptor on T cells and LFA-3 on antigen-presenting cells. Alefacept has shown efficacy in other T cell mediated diseases and has a favorable safety profile, making it an attractive candidate in T1D. The T1DAL study tested whether Alefacept was able to slow the progression of T1D in new onset subjects compared to placebo-treated subjects.
This will be the first presentation of primary endpoint data from this study.
Alice Long, PhD (Benaroya Research Institute) will speak about the IL-2/RAPA study, “Proleukin® and Rapamune® in Type 1 Diabetes Mellitus.” One of the first combination trials in T1D, this Phase I study examined the safety of IL-2 (Proleukin), a cytokine known to induce regulatory T cells, in combination with rapamycin (Rapamune®), which inhibits proliferation of T helper and T effector cells. Results from this study were published in Diabetes last year.