Effects of GRA in Patients With Type 1

NCT04779645 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: UC-MEDJP-04
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effects a Glucagon Receptor Antagonist (GRA), has on Insulin Sensitivity, Cardiovascular risks (CVD), and Ketone body formation in participants with Type 1 diabetes. The participants will complete blood tests, tests to measure energy expenditure, CVD risks, and insulin resistance. These tests will be performed prior to start of treatment and again after 12-weeks of treatment with the GRA (called REMD-477).

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (9)

• Metabolic Clearance Rate of Insulin

  The change from baseline in calculated metabolic clearance rate of insulin as measured by the 2-step Hyperinsulinemic-Euglycemic Clamp.

  12-Weeks

• Rate of Resting Energy Expenditure (REE)

  Change from baseline REE as measured by indirect calorimetry.

  12-Weeks

• Change in Beta-hydroxybutyrate (BHB) Level

  The change from baseline in peak BHB production as measured by the insulin withdrawal challenge.

  12-Weeks

• Change in Free Fatty Acid (FFA) Level

  The change from baseline in peak FFA production as measured by the insulin withdrawal challenge.

  12-Weeks

• Change in mRNA Expression

  The change from baseline in gene mRNA expression as measured by adipose and muscle tissue samples.

  12-Weeks

• Change in Peripheral Macrovascular Vasodilation

  The change from baseline in post-stimulus vessel diameter as measured by flow mediated dilation.

  12-Weeks

• Change in Peripheral Microvascular Vasodilation

  The change from baseline in reactive hyperemia index as measured by reactive hyperemia-peripheral arterial tonometry (RH-PAT).

  12-Weeks

• Change in Cardiovascular Disease (CVD) Risk Markers.

  The change in pg/mL from baseline in CVD risk markers (SAA, CRP, VCAM-1 and ICAM-1) as measure by blood samples.

  12-Weeks

• Change in Cardiovascular Disease (CVD) Risk Markers.

  The change in ng/mL from baseline in CVD risk markers (Thrombomodulin, ICAM-3, E-Selectin and P-Selectin) as measure by blood samples.

  12-Weeks

Study Arms (2)

GRA (REMD-477) Group

EXPERIMENTAL

Once weekly, subcutaneous injection of 70mg REMD-477 (in 1 mL solution) for up to 12 weeks.

Drug: REMD-477

Placebo Group

PLACEBO COMPARATOR

Once weekly, subcutaneous injection of 1mL saline solution for up to 12 weeks.

Drug: Placebo

Interventions

REMD-477 DRUG

12-Week, once weekly subcutaneous injection with 70mg REMD-477

GRA (REMD-477) Group

Placebo DRUG

12-Week, once weekly subcutaneous injection with placebo

Placebo Group

Eligibility Criteria

• Age: 18 Years - 65 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 65 years old, inclusive, at the time of screening;
• Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing 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 for \> 5 years;
• Treatment with a stable insulin regimen for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump;
• Currently using a Continuous Glucose Monitoring (CGM) system;
• HbA1c ≤ 8.5 % at screening;
• A minimum weight of 50kg;
• 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 and/or liver disease;
• Clinically significant diagnosis of anemia;
• Body Mass Index (BMI) \< 18.5 kg/m2 and/or weight less than 50kg;
• 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;
• 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
• REMD Biotherapeutics, Inc.: collaborator

Study Sites (1)

UC San Diego Altman Clinical & Translational Research Institute

La Jolla, California, 92037, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

volagidemab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Single-center, double-blind, placebo-controlled, multi-dose study.

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 3, 2021
• Study Start: July 31, 2021
• Primary Completion: July 17, 2024
• Study Completion: December 31, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)