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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Administered by SC injection once weekly for 6 weeks
Altman Clinical and Translational Research Institute
San Deigo, California, United States
Diablo Clinical Research
Walnut Creek, California, United States
Change in Time to glucagon treatment success at Week 6.
The primary outcome of the study is the change in time to glucagon treatment success, defined as an increase in plasma glucose of ≥20 mg/dL from the glucose nadir after receiving glucagon during insulin-induced hypoglycemia, from baseline to Week 6.
Time frame: 6 weeks
Blood glucose response to glucagon rescue treatment during insulin-induced hypoglycemia.
Percentage of subjects achieving glucagon treatment success, defined as an increase in plasma glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from the glucose nadir within 30 minutes of receiving glucagon during insulin-induced hypoglycemia, at Week 6.
Time frame: 6 weeks
Treatment emergent adverse events (AEs)
The subject incidence rates of AEs will be tabulated by system organ class, preferred term, and severity grade for all treatment emergent, serious, treatment related, and serious treatment related AEs.
Time frame: 12 weeks
Hypoglycemia symptoms - Edinburgh Hypoglycemia Scale
Results of the Edinburgh Hypoglycemia Scale will be summarized over Intent-to-Treat (ITT) set using descriptive statistics by visit (baseline, week 6) and timepoint (baseline, t = 15, 30, 45, and 60 min after glucagon administration for Edinburgh Hypoglycemia Scale). Changes from baseline in Edinburgh hypoglycemia scale will be summarized similarly.
Time frame: 6 weeks
Hypoglycemia symptoms - Clarke Survey
Results of the Clarke Survey will be summarized over Intent-to-Treat (ITT) set using descriptive statistics by visit (baseline, week 6). Changes from baseline in Clarke Survey will be summarized similarly.
Time frame: 6 weeks
Hypoglycemia symptoms - Gold Questionnaire
Results of the Gold Questionnaire will be summarized over Intent-to-Treat (ITT) set using descriptive statistics by visit (baseline, week 6). Changes from baseline in Gold Questionnaire will be summarized similarly.
Time frame: 6 weeks
Change from baseline in hemoglobin A1c (HbA1c) at Week 6.
Change from baseline in hemoglobin A1c (HbA1c) at Week 6, after repeated doses of volagidemab
Time frame: 6 weeks
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