TrialNet-Led, NIH-Sponsored, Breakthrough Study Reveals Columbia-Originated Teplizumab Can Slow the Progression of Type 1 Diabetes

Type 1 Diabetes TrialsiteN

Provention Bio’s therapy, teplizumab, effectively slows the progression of type 1 diabetes in high risk individuals, according to the results of a recent TrialNet led, National Institutes of Health (NIDDK) funded study.

This is the first study to evidence that type 1 diabetes can be delayed by two or more years among people who are at high risk. The results of this important study were recently published in The New England Journal of Medicine and presented at the American Diabetes Association Scientific Sessions in San Francisco.

The Study

The study involves teplizumab, an anti-CD3 monoclonal antibody, and was conducted by Type 1 Diabetes TrialNet, an international collaboration aimed at discovering ways to delay or prevent type 1 diabetes.  The research team enrolled 76 participants aged 8-49 who were relatives of people with type 1 diabetes, had at least two types of diabetes-related autoantibodies (proteins made by the immune system) and abnormal glucose (sugar) tolerance.

The investigators randomly assigned participants to either the treatment group, which received a 14-day course of teplizumab, or the control group, which received a placebo. All participants received glucose tolerance tests regulatory until the study was completed, or until they developed clinical type 1 diabetes-whichever came first.

The Results Thus Far

During the trial, 72% of the participants in the control group developed clinical diabetes, compared to only 43% in the teplizumab group. The median time for people in the control group to develop clinical diabetes was just over 24 months, while those who developed clinical diabetes in the treatment group had a median time of 48 months before progressing to diagnosis.

Comment on the Findings: “Striking Results”

Lisa Spain, PhD and Project Scientist from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), sponsor of TrialNet, noted “The difference in outcomes was striking. This discovery is the first evidence we’ve seen that clinical type 1 diabetes can be delayed with early preventative treatment.”  Spain continued, “The results have important implications for people, particularly youth, who have relatives with the disease, as these individuals may be at high risk and benefit for early screening and treatment.”

Study Investigator Network : Type 1 Diabetes TrialNet (an international network)

Type 1 Diabetes TrialNet is an international collaboration aimed at discovering ways to delay or prevent type 1 diabetes.  It involves sites from the U.S. and Canada through Europe, Australia and New Zealand. The TrialNet family is made up of physicians, scientists and healthcare teams at the forefront of type 1 diabetes research. Many of them have a personal connection to type 1 diabetes, fueling their passion to help families affected by T1D. They are also the largest international network of T1D researchers worldwide.

The goal of the TrialNet Natural History Study of the Development of Type 1 Diabetes is to enhance the understanding of the demographic, immunologic and metabolic characteristics of individuals at risk for developing type 1 diabetes.

They offer free Pathway to Prevention screening to relatives of people with T1D to detect the disease in its earliest stages—often years prior to symptoms. With the help of thousands of volunteers participating in their clinical studies, they learn more about how T1D develops and test news ways to maintain insulin production before and after diagnosis.

Study locations in the network are listed in ClinicalTrials.gov.  The Study Chair is Carla J. Greenbaum, MD Benaroya Research Institute.

Study Drug: Teplizumab

Teplizumab, also known as PRV-031 is a humanized anti-CD3 monoclonal antibody that is being evaluated for treatment and prevention of type 1 diabetes mellitus (T1DM) by the biotech venture Provention Bio. The investigative therapy has also been evaluated for the treatment of renal allograft rejection, for induction therapy in islet transplant recipient and for psoriatic arthritis.

Teplizumab was originally developed at Columbia University and then further developed by Macrogenics, Inc. with a collaboration with Eli Lilly to conduct the first Phase 3 clinical trial in early-onset type 1 diabetes.

What are Provention Bio Plans with the Drug?

Provention Bio has announced plans to re-start Phase 3 development in T1D after the initial Phase 3 trial conducted with Macrogenics failed to meet the primary endpoint. They also revealed efficacy signals in C-peptide in the totality of patients in other endpoints in the sub-populations now objects of the Provention Bio study.

TrialNet Funding

TrialNet is funded by the NIH, primarily through the Special Statutory Funding Program for Type 1 Diabetes. Additional support came via the JDRF and the American Diabetes Association. Macrogenics and Provention Bio donated the study drugs and provided funds for additional site monitoring.