829-P: Once-Weekly Insulin SHR-3167 in Healthy Subjects and Type 2 Diabetes Mellitus Participants—A Phase 1, Randomized, Single- and Multiple-Ascending Dose Study

Introduction and Objective: SHR-3167, a novel once-weekly insulin, is designed to provide a long-acting option. Here, we present the outcomes of a phase 1 trial of SHR-3167 in healthy subjects and type 2 diabetes mellitus (T2DM) participants (pts). Methods: This randomized, multicenter, phase 1 trial comprised a placebo-controlled, double-blind single ascending dose (SAD) part and a positive-controlled, open-label multiple ascending dose (MAD) part. In SAD, 28 healthy volunteers were randomized (3:1) to receive a subcutaneous (sc) injection of SHR-3167 (0.5, 2, 8, and 20 mg) or placebo, and 16 T2DM pts inadequately controlled with oral antidiabetic drugs were randomized (3:1) to receive SHR-3167 (25 and 50 mg, sc) or placebo. In MAD, 18 T2DM pts on daily basal insulin were randomized (2:1) to switch to weekly SHR-3167 (10 and 20 mg, sc) or daily insulin glargine (IGlar, sc) for 6 weeks. Primary endpoints were safety and tolerability. Results: The majority of adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Following fixed dose of SHR-3167, hypoglycemia occurred in 4 of 24 (16.7%) T2DM pts (3 pts in level 1; 1 pt in level 2). In SAD, median Tmax of SHR-3167 was 3.0-5.5 days, and geometric mean t1/2 was 10.4-11.9 days. SHR-3167 exposure increased almost proportionally in T2DM pts. Steady state concentration was reached around 6 weeks after administration in MAD. In T2DM pts in SAD, fasting plasma glucose (FPG) continuously decreased from baseline over 15 days. Mean FPG reduction on day 8 was 2.1 and 2.3 mmol/L with SHR-3167 at 25 and 50 mg, compared with 0.9 mmol/L with placebo. In MAD, SHR-3167 had a dose-dependent manner in decreasing HbA1c. Reduction in HbA1c on day 43 was 0.60% with SHR-3167 at 20 mg and 0.33% with SHR-3167 at 10 mg, compared with 0.37% with IGlar. Conclusion: Once-weekly insulin SHR-3167 showed good tolerability, favorable pharmacokinetics, and evident glucose-lowering effects. Disclosure Y. Liu: None. H. Zhou: None. C. Meng: None. T. Pan: None. Y. Wang: None. K. Shen: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Dong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Xiang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Ma: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Funding Jiangsu Hengrui Pharmaceuticals Co., Ltd.