University of South Florida

USF Health scientists coordinate clinical trial of drug that receives FDA approval to delay the onset of type 1 diabetes

Scientists at the USF Health Morsani College of Medicine helped coordinate the study of a drug approved Thursday by the U.S. Food and Drug Administration (FDA) to delay the onset of type 1 diabetes.

Approval of the medication, called Tzield (teplizumab-mzwv), marks the first time that a therapy has been shown to delay symptoms in patients at high risk for type 1 diabetes, an autoimmune disease in which the body’s immune system mistakenly attacks and destroys cells that produce insulin. Insulin is the hormone the body uses to regulate blood sugar. In clinical trials, patients who received Tzield injections took an average of two years longer to move from the early stages of the disease to experiencing symptoms.

“I am very proud of our team at USF that played a key role in the approval of teplizumab as a treatment to delay type 1 diabetes onset in at-risk individuals,” said Dr. Jeffrey Krischer, Ph.D., vice chair for research, Department of Internal Medicine, Director of the USF Health Informatic Institute and USF Health Endowed Chair in Diabetes Research. The study was conducted by TrialNet, funded mainly by the  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) through the Special Diabetes Program. “Approval by the FDA shows great confidence in our ability to design and conduct clinical trials that can lead to bringing new treatments to patients.”

The FDA approved the use of Tzield after a clinical trial of 76 patients who had stage 2 diabetes, in which the disease already has begun destroying cells that make insulin. These early stages of type 1 diabetes, or T1D, can be detected with a blood test. The patients had not yet progressed to stage 3 of the disease, in which they start experiencing such symptoms as frequent urination, excessive thirst, weight loss, and fatigue. Once patients start experiencing these symptoms, they face a lifetime of blood sugar monitoring and insulin injections.

“The onset of Stage 3 T1D is a life-changing moment – once insulin-producing cells are no longer capable of maintaining normal glycemic control, this irreversible condition can lead to the need, in just one year, for a patient, 1,460 finger sticks to check blood glucose levels, around 1,100 insulin injections, and experiencing an average of 127 episodes of hypoglycemia,” said Dr. Eleanor Ramos, chief medical officer at Provention Bio, Inc., in a press release. “These complications can cause stress, fear, and anxiety in patients as they work to manage their T1D diagnosis and provide perspective on the meaning of a delay in the onset of Stage 3.” Provention Bio, Inc., is the maker of Tzield.

During the trial, patients were chosen at random to receive either Tzield or a placebo once each day via intravenous infusion for 14 days. Patients who received Tzield took an average of 25 months longer to move to stage 3 diabetes than those who received the placebo. (Neither patients nor their doctors knew which patients were receiving the medication.) Patients included both adults and children aged 8 and older.

Tzield appears to delay the onset of type 1 diabetes by deactivating immune cells that attack insulin-producing cells, while increasing the proportion of cells that help moderate the immune response.

Laboratory research on the drug was done at Yale University. TrialNet investigators, including USF staff, designed and implemented the clinical trial. USF staff coordinated the TrialNet trial and analyzed the results, which were published in the New England Journal of Medicine. TrialNet is comprised by the USF data coordinating center and a network of 22 clinical research centers focused on type 1 diabetes. These clinical sites across the country consented and enrolled participants. The drug will soon be available to patients in the U.S.

USF researchers Henry Rodriguez, MD, professor of Pediatrics and in the Health Informatics Institute, and Brian Bundy, Ph.D., associate professor in the USF Health Informatics Institute, were co-authors on the study.

The success of this trial opens the door for new drugs that target mechanisms of diabetes initiation and progression being pursued by TrialNet. It also adds to the imperative to screen individuals earlier in the disease process that can lead to interventions currently being tested to add to these results.

The most common side effects of Tzield include decreased levels of certain white blood cells, rash and headache, according to the FDA. The FDA also included warnings and precautions for premedicating and monitoring for symptoms of Cytokine Release Syndrome, risk of serious infections, decreased levels of a type of white blood cell called lymphocytes, and risk of hypersensitivity reactions. All age-appropriate vaccinations should be administered before starting Tzield, and patients should avoid concurrent use of live, inactivated and mRNA vaccines with Tzield, according to the FDA.

In addition to NIDDK and industry funding, the trial was supported by the National Institute of Allergy and Infectious Diseases; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Center for Research Resources; the Juvenile Diabetes Research Foundation; and the American Diabetes Association.

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