Phase 2 Trial of Icovamenib in Participants With Type 2 Diabetes Who Are Not Achieving Glycemic Targets

This study is a 52-week, Phase 2 trial is designed to examine whether treatment with icovamenib in participants with T2D who are currently on standard-of-care antihyperglycemic medications (metformin, SGLT2 inhibitor, alogliptin, or sitagliptin) plus lifestyle management will result in a greater reduction in HbA1c than those therapies alone. The trial investigates participants who have been on a stable dose of their antihyperglycemic medication(s) for at least 3 months prior to screening whose HbA1c remains above the target established by the American Diabetes Association (ADA).

Inclusion criteria

• Males or females, age ≥18 years and ≤70 years
• Diagnosed with T2D
• Have been treated with lifestyle management with 1 to 3 antihyperglycemic medications: metformin, SGLT2i, alogliptin, or sitagliptin with a stable dose for at least 3 months prior to screening (participants taking metformin must be on a minimum stable dose of ≥500 mg/day)
• Have HbA1c ≥7.5 and ≤10.5%
• Have a BMI ≤32 kg/m2
• Female participants of childbearing potential must have a negative pregnancy test, must be non-lactating and must be willing to have additional pregnancy tests during the study.
• Willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Exclusion criteria

• Have type 1 diabetes mellitus or a secondary form of diabetes
• Have a history of diabetic ketoacidosis or hyperosmolar coma in the 6 months prior to screening
• Have positive GAD autoantibody result at screening
• Have a history of severe hypoglycemia (defined by the occurrence of hypoglycemia symptoms requiring the assistance of another person for recovery) in the 6 months prior to screening or a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms as judged by the investigator
• Have personal or family history (first-degree relative) of MEN16. Use of GLP-1 RA, dual GIP/GLP-1 RA, sulfonylureas, meglitinides, thiazolidinediones, alpha glucosidase inhibitor, [linagliptin, saxagliptin (these 2 are drugs within DPP4I class)], bile acid sequestrants, dopamaine-2 agonists, amylin, or insulin in the 3 months prior to screening
• Have FPG ≥240 mg/dL
• Have fasting triglyceride ≥500 mg/dL
• Have an eGFR <75 mL/min/1.73 m2 by the CKD-EPI Creatinine Equation at screening
• Have impaired liver function, defined as screening AST or ALT >1.2×ULN, and/or total bilirubin >ULN