Combination Adjunctive Therapy to Address Multiple Metabolic Imbalances in Type 1 Diabetes

NCT ID: NCT05696366

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-09
• Study Completion Date: 2028-01-31

Brief Summary

This is a single site, double-blind, placebo-controlled, crossover trial to quantify the effects of combination adjunctive therapy on glycemic control, ketogenesis during insulinopenia, insulin resistance, and diabetes burden and quality of life.

Detailed Description

This is a single site, double-blind, placebo-controlled, crossover trial to quantify the effects of combination adjunctive therapy on glycemic control, ketogenesis during insulinopenia, insulin resistance, and diabetes burden and quality of life.

Up to 22 adult participants with type 1 diabetes (T1D) will be enrolled with at least 16 participants completing the study in full. After screening, baseline data (A1c, CGM, ambulatory insulin dosing, ambulatory ketones [fasting and after infusion set change], and psychosocial questionnaires) will be collected and participants will complete an insulin withdrawal test (IWT) and a hyperinsulinemic-euglycemic clamp (HEC) with indirect calorimetry (IDC). Participants will then receive 12-week insulin-adjunctive treatments with both: (1) SGLTi (sotagliflozin 200 mg daily) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg weekly), in a random-order, cross-over design with a 14-week washout period between treatment periods. Throughout the treatment periods subjects will be seen weekly in clinic for medication dosing (GRA or placebo) and download/review of CGM, insulin, and ketone data. At the end of each treatment period, the baseline studies will be repeated. Subjects will return for a safety follow up visit 6 weeks after the final GRA or placebo dose.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

sotagliflozin 200 mg

Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.

Sotagliflozin is a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 (SGLT1/2) inhibitor.

Group Type: ACTIVE_COMPARATOR

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin is a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 (SGLT1/2) inhibitor.

volagidemab 35 mg

Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.

Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA).

Group Type: ACTIVE_COMPARATOR

Volagidemab

Intervention Type: DRUG

Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA).

Placebo

Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods.

Group Type: PLACEBO_COMPARATOR

Volagidemab

Intervention Type: DRUG

Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA).

Interventions

Sotagliflozin

Sotagliflozin is a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 (SGLT1/2) inhibitor.

Intervention Type: DRUG

Volagidemab

Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men and women between the ages of 18 and 70 years old, inclusive, at the time of screening;

2. 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;

3. Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;

4. Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;

5. Treatment with a stable insulin regimen for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump or hybrid closed loop system;

6. Currently using a Continuous Glucose Monitoring (CGM) system;

7. A1c > 7% and ≤ 10%

8. eGFR ≥ 60 mL/min/1.73m²;

9. Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria

1. History or evidence of clinically significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;

2. History of pancreatitis, medullary thyroid carcinoma or liver disease;

3. Clinically significant diagnosis of anemia (Hemoglobin < 9 g/dl at screening);

4. Body Mass Index (BMI) < 18.5 kg/m2 and/or weight <50kg;

5. Body Mass Index (BMI) > 35 kg/m2

6. Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;

7. Current or recent (within 1 month of screening) use of diabetes medications other than insulin; (examples include GLP-1 RA, SGLT-2i, Pramlintide, Metformin);

8. Women who are pregnant or lactating/breastfeeding;

9. Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;

10. Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lexicon Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Breakthrough T1D

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Schafer Boeder

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UC San Diego Altman Clinical & Translational Research Institute

La Jolla, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Schafer Boeder

Role: CONTACT

sboeder@health.ucsd.edu

858-246-2161

Todd May

Role: CONTACT

tmay@health.ucsd.edu

858-246-2169

Facility Contacts

CDRC Manager

Role: primary

t1dresearch@health.ucsd.edu

858-246-2169

Other Identifiers

806355

Identifier Type: -

Identifier Source: org_study_id