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

NCT05696366 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 806355
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  Quantify the effects of combination adjunctive therapy on glycemic control. Though it has limitations, the HbA1c remains the gold standard measurement of glycemic control in diabetes.

  12 weeks

Secondary Outcomes (2)

• Change in percent time in range (70-180 mg/dl) by CGM

  12 weeks

• Change in subject self reported ambulatory insulin dosing

  12 weeks

Study Arms (3)

sotagliflozin 200 mg

ACTIVE COMPARATOR

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.

Drug: Sotagliflozin

volagidemab 35 mg

ACTIVE COMPARATOR

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).

Drug: Volagidemab

Placebo

PLACEBO COMPARATOR

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.

Drug: Volagidemab

Interventions

Sotagliflozin DRUG

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

sotagliflozin 200 mg

Volagidemab DRUG

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

Placebo; volagidemab 35 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 18 and 70 years old, inclusive, at the time of screening;
• 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 6 months after the end of the treatment period;
• Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
• 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;
• Currently using a Continuous Glucose Monitoring (CGM) system;
• A1c \> 7% and ≤ 10%
• eGFR ≥ 60 mL/min/1.73m²;
• Able to provide written informed consent approved by an Institutional Review Board (IRB).

You may not qualify if:

• 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;
• History of pancreatitis, medullary thyroid carcinoma or liver disease;
• Clinically significant diagnosis of anemia (Hemoglobin \< 9 g/dl at screening);
• Body Mass Index (BMI) \< 18.5 kg/m2 and/or weight \<50kg;
• Body Mass Index (BMI) \> 35 kg/m2
• 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;
• Current or recent (within 1 month of screening) use of diabetes medications other than insulin; (examples include GLP-1 RA, SGLT-2i, Pramlintide, Metformin);
• Women who are pregnant or lactating/breastfeeding;
• Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• Lexicon Pharmaceuticals: collaborator
• Breakthrough T1D: collaborator

Study Sites (1)

UC San Diego Altman Clinical & Translational Research Institute

La Jolla, California, 92037, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; volagidemab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Schafer Boeder

CONTACT

858-246-2161; sboeder@health.ucsd.edu

Todd May

CONTACT

858-246-2169; tmay@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: January 25, 2023
• Study Start: September 9, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)