Phase II clinical trial to test the ability of a vaccine to reverse advanced type 1 diabetes has been approved by US authorities. The trial will investigate whether the generic vaccine bacillus Calmette-Guerin (BCG) will be able to clinically improve type 1 diabetes in adults between 18 and 60 years of age who will be having small, but detectable levels of insulin secretion from the pancreas.
Denise Faustman, director of the Massachusetts General Hospital (MGH) Immunobiology Laboratory and principal investigator of the study and her team were the first to record the reversal of advanced type 1 diabetes in mice and subsequently has completed a successful phase I human clinical trial of BCG vaccination. "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," said Faustman.
BCG has been already been approved by the FDA for vaccination against tuberculosis and for the treatment of bladder cancer. The vaccine is able to elevate the levels of the immune modulator tumour necrosis factor (TNF), which Faustman's team showed that it can temporarily eliminate both in humans and mice, the abnormal white blood cells which are responsible for the autoimmune type 1 diabetes. Increased TNF levels can stimulate the production of protective regulatory T cells.
In the phase I clinical trial, two injections of BCG in four weeks apart led to the temporary elimination of the diabetes-causing T cells and provided evidence of a transient return of insulin secretion.
Phase II clinical study will include frequent dosing over a longer time period to determine the potential of repeat BCG vaccination to ameliorate the autoimmune state and improve clinical parameters like HbA1c, a marker of average blood sugar control.
"In the phase I clinical trial, we demonstrated a statistically significant response to BCG, but our goal in phase II is to create a lasting therapeutic response," said Faustman.