glucagon rescue of insulin-induced hypoglycemia in adults with type 1 diabetes treated with volagidemab

Conditions: Type 1 Diabetes Mellitus

Summary: this trial is designed to evaluate the effect of glucagon receptor antagonism by volagidemab (once weekly) on glucose recovery from hypoglycemia after treatment with glucagon in adults with type 1 diabetes. after informed consent, screening procedures to establish subject eligibility will be performed within a period of 28 days. approximately 24 subjects with type 1 diabetes mellitus (t1dm) on stable doses of insulin will be enrolled. after enrollment, subjects will undergo a baseline hypoglycemia recovery procedure (with glucagon rescue). subjects will then receive volagidemab subcutaneously (sc) once weekly for 6 weeks. at the end of the treatment phase, subjects will undergo a second hypoglycemia recovery procedure. subjects will be followed for 6 weeks after the last volagidemab dose with a final end-of-study (eos) visit during week 12. the primary outcome will be the change in time to glucagon treatment success at week 6 versus baseline.


Eligibility criteria:
inclusion criteria: * receiving insulin for the treatment of documented diagnosis of t1dm for at least 2 years * body mass index (bmi) of 18.5 kg/m2 to 35.0 kg/m2 * on treatment with a stable insulin regimen for at least 8 weeks * currently using a continuous glucose monitoring (cgm) system * hba1c less than or equal to 10.0% * females of non-childbearing potential must be ≥1 year post-menopausal or documented as being surgically sterile. females of childbearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product * male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 3 months after the end of the treatment period * other inclusion criteria may apply. exclusion criteria: * history of type 2 diabetes, maturity onset diabetes of the young (mody), pancreatic surgery or chronic pancreatitis * pancreas, pancreatic islet cells, or renal transplant recipient * t1dm treatment with any other antihyperglycemic drug (e.g., metformin, alpha- glucosidase inhibitors, sglt-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of day 1 * occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to day 1 * myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident ≤12 weeks * indication of liver disease * current signs and symptoms of anemia * untreated eating disorders such as bulimia or anorexia nervosa * history of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia (men) or family history of men. * treatment with systemic corticosteroids within 30 days of day 1, or planned initiation of such therapy during the study. * medical history of cancer or treatment for cancer in the last five years * women who are pregnant, nursing, or who plan to become pregnant while in the trial * other exclusion criteria may apply