Glucagon Rescue of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes Treated With Volagidemab

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Glucagon Rescue of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes Treated With Volagidemab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06272695
• Other study ID #: R477-203
• Status: Recruiting
• Phase: Phase 1
• Start date: February 15, 2024
• Est. completion date: June 15, 2025

Study information

• Verified date: February 2024
• Source: REMD Biotherapeutics, Inc.
• Contact: Zung Thai, MD
• Phone: 415-225-9338
• Email: zungthai[@]remdbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 72 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes Mellitus

Intervention

Biological:
• Volagidemab
Administered by SC injection once weekly for 6 weeks

Locations

Country	Name	City	State
United States	Altman Clinical and Translational Research Institute	San Diego	California
United States	Diablo Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
REMD Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 weeks
Secondary	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.	6 weeks
Secondary	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.	12 weeks
Secondary	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.	6 weeks
Secondary	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.	6 weeks
Secondary	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.	6 weeks
Secondary	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	6 weeks