Denise L. Faustman, MD, PhD, announced the phase 2 trial during the 75th Scientific Sessions of the American Diabetes Association. The 150 patients will be studied for 5 years.
An old vaccine to prevent tuberculosis could have a new use, with the news that FDA has approved a phase 2 clinical trial to learn whether it can reverse type 1 diabetes mellitus (T1DM).
Denise L. Faustman, MD, PhD, director of the Massachusetts General Hospital (MGH) Immunobiology Laboratory and principal investigator of the study, announced the news during her presentation, “Low-Levels of C-Peptide Have Clinical Signficance for Established Type 1 Diabetes,” which took place during the 75th Scientific Sessions of the American Diabetes Association, which conclude today in Boston.
The vaccine being studied is a generic, bacillus Calmette-Guerin (BCG). The MGH trial will enroll 150 patients with advanced disease for the phase 2 trial; this step of the research process determines whether there is enough evidence of safety and efficacy to move forward with a phase 3 trial with a larger group of patients. A successful phase 3 trial is needed for FDA approval.
BCG has been in clinical use for 90 years, so there is plenty of safety data for the drug. It is currently approved by FDA for vaccination against tuberculosis and for the treatment of bladder cancer. The vaccine works by elevating levels of the immune modulator tumor necrosis factor (TNF), which Dr Faustman's research team has shown can temporarily eliminate the abnormal white blood cells responsible for autoimmune T1DM. These tests have been performed in mice and in humans. Increased TNF levels also stimulated production of protective regulatory T cells.
The 5-year, double-blinded trial will examine whether repeated use of the BCG vaccine can improve T1DM for adults who still have detectable levels of insulin secretion from their pancreas. Patients will be randomized to receive either the study drug or placebo, and will receive 2 injections 4 weeks apart, then a single injection once a year for 4 years. The primary endpoint will be improved results on a test of glycated hemoglobin (A1C).
Dr Faustman’s research team has previously shown the reversal of T1DM in mice, which led to a successful phase 1 human clinical trial of the BCG vaccine for this purpose. "We have learned a lot since the early studies in mice—not just about how BCG works but also about its potential therapeutic benefits, similar to what are being seen in trials against other autoimmune diseases,” she said.
Faustman DL, Washer SLL, Hsu E, et al. Low levels of C-peptide have clinical significance for established type 1 diabetes. Diabetes. 2015; 64(suppl1) abstract 271-OR.