Breakthrough - T1DM and Chronic Kidney Disease

This study is funded by Breakthrough T1D (formerly the Juvenile Diabetes Research Foundation) and Emerald Clinical Trials will be acting as the clinical research organization (CRO) for this study, overseeing data integrity, compliance and monitoring clinical trial activity. They will help with development of all regulatory and fully supporting University of Miami. Islet cells are the specialized cells in the pancreas that produce insulin. In this study, islet cells will be collected from the pancreas of a deceased organ donor in a special laboratory at University of Chicago and then transplanted into the body at the University of Chicago hospital. The goal of this study is to see whether these transplanted islet cells can take over insulin production for the body. The study team will evaluate how well make insulin and how well controlled blood sugar is after the transplant. Islet transplantation has been performed and continuously optimized under clinical studies at the University of Chicago for the past 20 years. During this time, several new, potentially more effective and less toxic combinations of immunosuppressive medications have been evaluated. More recently, Tegoprubart has been tested in a small number of patients with T1D and only mild kidney dysfunction, in combination with mycophenolic acid (Myfortic). Given the promising preliminary results, Tegoprubart is now being studied in pancreatic cell transplantation together with either mycophenolic acid (MPA) or everolimus as part of the immunosuppressive regimen also in patients, who were previously ineligible for islet transplantation due to more advanced kidney dysfunction. The islet transplant procedure involves inserting a thin, flexible tube called a catheter through a small cut in the upper abdomen. A radiologist uses x-rays and ultrasound to guide the catheter into the portal vein of the liver where the islet cells are delivered. This study of islet transplantation will test to see if islet transplantation is safe and effective; performing this study will help us find if this new medication Tegoprubart, combined with either MPA or everolimus and other medication the provider has been using routinely so far, would protect sufficiently islet transplant from the destruction by the immune system, allowing to stop insulin and have improved blood glucose control. At the same time, the providers will observe if these therapies are safe and other patients participating in the study. Because these islet cells came from another person, the immune system may recognize them as foreign and attack them. Standard immunosuppressive medicines (Anti-thymocyte globulin \[ATG\] or Basiliximab and Etanercept) with either MPA or everolimus will be used to help prevent the body from attacking the transplanted islet cells. Immunosuppressive medicines may also be called anti-rejection medicines. Tegoprubart will be given in combination with these standard immunosuppressive medicines to test whether the investigational drug is safe, tolerable, and efficacious. The effect of the combination of Tegoprubart with other immunosuppressant medications has not been previously tested. Tegoprubart is a monoclonal antibody. Antibodies are Y-shaped proteins that are produced naturally by their immune system to attack and fight foreign substances that cause illness. Monoclonal antibodies are man-made proteins manufactured to serve as substitute antibodies to fight diseases. Monoclonal antibodies can restore, enhance, or mimic (copy) the immune system's attack process; they can also tone down the immune system. Tegoprubart is thought to work by dampening down our immune system so that it will be less likely to attack the transplanted cells. For other types of transplants, like kidneys, a drug called a calcineurin inhibitor is usually used to prevent rejection. That class of drugs can be toxic to islet cells. Tegoprubart is an experimental agent that is anticipated to prevent rejection without harming the islet cells. This study will test this hypothesis. Early results from a recent kidney transplant study using Tegoprubart with Myfortic show that Tegoprubart appears to be less harmful to the insulin-producing cells, the kidneys, and the nervous system compared with tacrolimus and is comparable in prevention of rejection and risk of infectious and developing blood clots in blood vessels. The Tegoprubart for this study has been provided by Eledon Pharmaceuticals.