Simplici-T1—First Clinical Trial to Test Activation of Glucokinase as an Adjunctive Treatment for Type 1 Diabetes

Abstract

TTP399 is an oral liver selective Glucokinase Activator (GKA). Because it exhibits an insulin-independent mechanism of action, it may be suitable as an adjunctive treatment for type 1 diabetes (T1DM). In clinical trials in type 2 diabetes (T2DM), TTP399 has shown significant reduction in postprandial glucose, increased percentage time in range and decreased percentage time in hypo or hyperglycemia. Moreover, TTP399 significantly reduced HbA1c without significant hypoglycemia, dyslipidemia, or ketoacidosis. The Simplici-T1 trial (NCT03335371) is an adaptive three-part (sentinel, learning phase and confirming phase) Phase 1b/2 Proof of Concept study designed to explore the effect of TTP399 as adjunctive therapy for the treatment of T1DM. The aims of the study are to: (1) evaluate the safety of TTP399 and (2) evaluate whether TTP399 can replace or reduce mealtime insulin bolus and improve A1c in patients with T1DM. The sentinel phase, an open label, dose escalation study in 5 adults with T1DM on insulin pump therapy and continuous glucose monitoring (CGM), showed that TTP399 was well tolerated. No incidents of severe hypoglycemia or diabetic ketoacidosis were observed. When compared to baseline, trends toward improved glycemic control while reducing insulin dose (Table) were observed with TTP399 treatment, supporting continuing to the randomized, placebo controlled phase of the study. Disclosure J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. C. Valcarce: Employee; Self; VTV Therapeutics. J.L. Freeman: Employee; Self; VTV Therapeutics. Stock/Shareholder; Self; VTV Therapeutics. Stock/Shareholder; Spouse/Partner; VTV Therapeutics. I. Dunn: Employee; Self; VTV Therapeutics. C. Dvergsten: Employee; Self; VTV Therapeutics. M. Kirkman: Research Support; Self; Bayer AG, Theracos, Inc.. Consultant; Self; National Institutes of Health. Research Support; Self; National Institutes of Health, Centers for Disease Control and Prevention. A. Kass: None. J. Diner: None. K.A. Bergamo: None.