Riley Children’s Health selected as site for WAVE T1D testing combination therapy to delay onset

Riley Children’s and Indiana University School of Medicine’s selection as a trial site continues a long history of leadership in Type 1 diabetes clinical trials. Most notably, IU School of Medicine and Riley were key contributors in the original study of teplizumab, the first FDA-approved drug to delay onset of Type 1 diabetes.

“The success of teplizumab has really invigorated research in the field,” said Jamie L. Felton, MD, pediatric endocrinologist at Riley Children’s and a basic science researcher in the Herman B Wells Center for Pediatric Research at IU School of Medicine. “It’s led to amazing results for some patients, motivating us to continue exploring potential therapies like this that enable the body to hold onto its own insulin, with the ultimate goal of prevention.”

Targeting patients ages 9 to 20 with newly diagnosed T1D, the trial examines the use of immune modulator anti-thymocyte globulin (ATG), followed by either adalimumab, an anti-inflammatory drug, or verapamil, a calcium channel blocker thought to support beta cells. When used alone in clinical trials, ATG has shown some benefit in transiently depleting T cells but not enough to move forward with FDA approval.

“We know there is some temporary benefit with ATG, and we also know there is a complex immune response at work, so the focus of WAVE T1D is to look at therapies in combination, targeting different parts of the immune response at the same time,” said Dr. Felton. “If we can show that this therapy works as well as or better than teplizumab in preserving C-peptide, it will have significant implications for patients.”

One huge advantage, Dr. Felton explained, involves duration of therapy. Treatment with teplizumab requires a 14-day infusion. In the WAVE T1D protocol, ATG infusion is just two days. Both of the combination therapies being tested that follow the infusion can be administered at home over the course of the trial. WAVE T1D is also one of the first trials of its kind without a placebo.

“It’s a real challenge for patients who could be treated with a therapy that’s FDA approved to consider participating in a clinical trial where there’s a chance they could receive a placebo,” Dr. Felton said. “Now that we are seeing approval of immunomodulatory agents for T1D, WAVE T1D is a great example of how we need to be thinking carefully about how we structure clinical trials moving forward.”

In addition to facilitating clinical research at Riley Children’s, Dr. Felton is an independent investigator in the IU School of Medicine Center for Diabetes and Metabolic Diseases and the Wells Center. The scope of her research focuses on understanding the immune pathogenesis of Type 1 diabetes. With funding from both the National Institutes of Health and Breakthrough T1D, her lab studies the role of B cells in T1D and how their function is altered early in the disease course. Her grant-funded research also includes investigating how genetics change B cell function and how the disease progresses.

“Riley’s history of leadership in diabetes research and clinical care, along with IU’s commitment to fostering the development of early-career scientists, were two of the factors that drew me here,” said Dr. Felton, who joined Riley and IU School of Medicine in 2018. “There are also some really amazing women in medicine at IU and Riley serving as incredible role models and leaders.”

Riley Children’s is one of 17 international centers participating in TrialNet, a major research network focused on Type 1 diabetes prevention and treatment. In addition to its involvement in the original clinical trials of teplizumab, Riley Children’s was also one of the first pediatric programs in the Midwest to administer the FDA-approved treatment.

Learn more

Check out the Diabetes & Endocrinology section of the latest Riley Children’s Health annual report for more information about treatment, novel programs and research.