2862-LB: Phase II Clinical Trial of BCG Immunotherapy for Type 1 Diabetes with Juvenile Onset: Five-Year Analysis of Safety, HbA1c, Time in Range, and Insulin Use

Introduction and Objective: A Phase I clinical trial of 2 doses of bacillus Calmette-Guérin (BCG) in adults with type 1 diabetes (T1D) demonstrated induction of regulatory T cells and durable improvements in HbA1c from restored lymphoid glucose metabolism. Pancreatic insulin did not contribute to glucose control. Two additional open-label clinical trials of BCG in adults with T1D showed similar reductions in HbA1c. A Phase II, double-blind, placebo-controlled trial of BCG in 150 subjects with juvenile-onset T1D or latent autoimmune diabetes in adults (LADA) was undertaken with the primary endpoint of improved HbA1c (NCT02081326). Here we present 5-year data on subjects in the Phase II trial with juvenile-onset T1D. Methods: Adults with T1D (age of onset < 21 y) were followed for 5 years and received 6 doses of intradermal (ID) BCG (Tokyo 174 strain, Japan BCG Laboratory, Japan) or placebo (n=34 BCG; n=24 placebo). The primary outcome was reduction in HbA1c. Secondary outcomes were insulin use, time with normoglycemia, autoantibody levels, and stimulated C-peptide secretion. Results: BCG was safe and statistically significantly reduced mean HbA1c levels from 7.84 ± 0.16% (Year 0) to 7.30 ± 0.22% (Year 5; P=0.0006). There was a statistically significant reduction in insulin use in the BCG-treated group, from 0.68 ± 0.04 U/kg/day (Year 0) to 0.63 ± 0.03 U/kg/day (Year 5; P=0.024). CGM data showed up to 183.7% improvement over baseline in time spent in normoglycemia (blood sugar 70-99mg/dL) with no increased episodes of hypoglycemia. C-peptide levels were low or non-detectable at enrollment and were not improved at Year 5. Conclusion: This study shows that multi-dose BCG is safe and lowers HbA1c, reduces insulin need, and improves time with normoglycemia without increases in hypoglycemic events in adults with juvenile-onset T1D. BCG’s therapeutic effect on blood sugar control is independent of pancreas function and is likely a durable correction of an underlying aerobic lymphoid metabolic defect. Disclosure D.L. Faustman: None. J. Braley: None. N. Hullavarad: None. E. Bulczynski: None. J. Dorsey: None. N. Kartsounis: None. L. Tran: None. B.J. Thach: None. H. Hayashi: None. D.A. Mounier: None. L. Adams: None. S. Bradley: None. S. Hashiguchi: None. H. Zheng: None. W.M. Kuhtreiber: None.