The five-year trial will investigate whether the generic vaccine bacillus Calmette-Guerin (BCG) can clinically improve type 1 diabetes in adults between 18 and 60 years of age who have small but still 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 document reversal of advanced type 1 diabetes in mice and subsequently completed a successful phase I human clinical trial of BCG vaccination.
She has now received approval from the US Food and Drug Administration (FDA) to launch the phase II trial. “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.
A generic drug with over 90 years of clinical use and safety data, BCG is currently approved by the FDA for vaccination against tuberculosis and for the treatment of bladder cancer. The vaccine is known to elevate levels of the immune modulator tumour necrosis factor (TNF), which Faustman’s team previously showed can temporarily eliminate in both humans and mice the abnormal white blood cells responsible for autoimmune type 1 diabetes. Increased TNF levels also stimulated production of protective regulatory T cells.
In the phase I clinical trial, which was published in 2012 in the journal PLOS Medicine, two injections of BCG spaced four weeks apart led to temporary elimination of diabetes-causing T cells and provided evidence of a small, transient return of insulin secretion.
The phase II clinical study will include more frequent dosing over a longer time period to determine the potential of repeat BCG vaccination to ameliorate the autoimmune state and improve clinical parameters such as HbA1c, a marker of average blood sugar control.
In the new trial, which will be double blinded and conducted at MGH, 150 adults with long-term type 1 diabetes will be randomised to receive two injections four weeks apart of either BCG or placebo and then a single injection annually for the next four years. “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.