11-LB: A Phase 2 Study of Liquid Stable Glucagon to Treat Hypoglycemia-Associated Autonomic Failure

Abstract

Objective: To evaluate a novel, ready-to-use, liquid stable, continuous subcutaneous (SC) glucagon infusion (CSGI; Xeris Pharmaceuticals) for the treatment of Hypoglycemia Associated Autonomic Failure (HAAF) in adults with type 1 diabetes (T1D). Method: This was a Phase 2 double-blind, randomized, placebo-controlled parallel trial in T1D adults with HAAF (Gold Score ≥4). Subjects were randomized to receive 1 month of high-rate CSGI (HCSGI, 80 μg/hour), low-rate CSGI (LCSGI, 20 μg/hour), or placebo. Epinephrine hormone response to hypoglycemia (assessed during stepwise hypoglycemia clamp procedure) and Gold Scores were measured at baseline, end of treatment, and both 3- and 6-months post-treatment. Results: Forty-nine subjects were randomized to receive treatment (HCSGI n=15; LCSGI n=18; placebo n=16). No statistically significant differences in mean epinephrine hormone response or Gold Scores were observed across treatment arms at end of treatment. Long-term follow-up of the subjects was stopped early. For completed follow-up clamps (31 subjects, 3 months; 22 subjects, 6 months), LCSGI did not exhibit differences to placebo. However, HCSGI 3 and 6 month mean epinephrine hormone responses were greater (p=NS) and Gold Scores improved [(-1.1±1.5 vs. 0.5±1.5; 3 months, p=NS) and (-1.2±1.5 vs. -0.6±0.9; 6 months, p=NS)]. The administration of CSGI was associated with mild to moderate nausea (5.9% for LCSGI and, 20% for HCSGI,) and vomiting (11.8% for LCSGI and 13.3% for HCSGI,). CSGI was not associated with pain, injection site reactions, or necrolytic migratory erythema. No related SAEs were reported. Conclusion: Compared to placebo in a small group of T1D adults with HAAF, HCSGI may exhibit improvements in Gold Score at both 3 and 6 months. Mean serum epinephrine may be a suboptimal biomarker of HAAF. CSGI was safely used with concomitant insulin, and there were no related SAEs. Disclosure J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. S. Nakhle: None. F. Ovalle: Research Support; Self; Gan & Lee Pharmaceuticals, Gilead Sciences, Inc., Lilly Diabetes, Novo Nordisk A/S, Sanofi, Xeris Pharmaceuticals, Inc. M.K. Junaidi: Employee; Self; Xeris Pharmaceuticals, Inc. N.C. Close: Employee; Self; EmpiriStat, Inc. V. Conoscenti: None. A. Nguyen: None.