A new ITN type 1 diabetes trial opened today at the first site, Sanford Health in Sioux Falls, SD. The EXTEND trial (Preserving Beta-Cell Function with Tocilizumab in New Onset Type 1 Diabetes) will test whether tocilizumab (ACTEMRA®; Genentech), an antibody that targets the interleukin-6 (IL-6) receptor, can slow disease progression and help maintain natural insulin production in adults with new-onset type 1 diabetes.
There are presently no treatments that can permanently halt or reverse the autoimmune-mediated destruction of insulin-producing beta cells in patients with type 1 diabetes. A few biologic agents that target immune pathways have shown promise in temporarily preserving insulin production in certain subsets of patients, but these effects are not long-lasting and there is a need for more durable therapies.
IL-6 is a cytokine that is known to mediate pro-inflammatory pathways in autoimmune diseases by both promoting effector responses as well as inhibiting regulatory functions. Tocilizumab, an anti-IL-6 receptor antibody, is approved in the US for rheumatoid arthritis and juvenile idiopathic arthritis, and has demonstrated efficacy in other autoimmune diseases. Preclinical data and ex-vivo studies with human cells support an important role for IL-6 in type 1 diabetes progression, and the EXTEND study will evaluate whether IL-6 blockade with tocilizumab can restore the immune balance in a way that helps preserve remaining beta cells. Interrupting and reprogramming autoimmune responses to induce long-lasting tolerance to islet antigens will likely require targeting multiple components of the immune system, and EXTEND will be a first step in evaluating anti-IL6 for future therapeutic strategies with other agents.
The EXTEND study is a phase II, multicenter, double-blind, placebo-controlled, randomized trial that will enroll 30 adults with type 1 diabetes (ages 18-45). Participants will receive either tocilizumab treatment or a placebo for 24 weeks. Insulin production will be measured using periodic mixed meal tolerance tests (MMTTs) throughout the study, with a final assessment at two years. If the EXTEND study demonstrates a prospect of clinical benefit in adults, the ITN plans to open the study to pediatric patients.