Combination GRA and SGLT-2i Treatment in Type 1 Diabetes

NCT04545411 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: UC-MEDJP-03
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot study for individuals with Type 1 Diabetes who are willing to add an SGLT-2i (Sodium-Glucose Cotransporter-2 Inhibitor) in combination with placebo or a GRA (Glucagon Receptor Antagonist) to their current diabetes treatment regimen. There will be 15 study visits over approximately 14 weeks in this cross-over study design. Treatment "A" consists of an SGLT-2i + GRA for 4 weeks and treatment "B" consists of an SGLT-2i + placebo for 4 weeks. All participants will complete both treatment "A" and treatment "B" with a 6-week washout period in between the treatments. Testing includes 3 insulin withdraw challenges, 3 muscle biopsies, 3 fat biopsies, 3 vascular ultrasounds along with blood collection and vitals.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (5)

• Change in Beta-hydroxybutyrate (BHB) Level

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

  4-Weeks

• Change in Glycemic Control

  The change from baseline glycemic control as measured by a 2-week average of CGM "time-in-range".

  4-Weeks

• Change in Glycemic Control

  The change from baseline glycemic control as measured by HbA1c.

  4-Weeks

• Change in Vascular Endothelial Function

  The change from baseline in vascular endothelial function as measured by flow mediated dilation (brachial artery diameter).

  4-Weeks

• Change in Vascular Endothelial Function

  The change from baseline in vascular endothelial function as measured by reactive hyperemia-peripheral arterial tonometry (reactive hyperemia index).

  4-Weeks

Study Arms (2)

Treatment A

ACTIVE COMPARATOR

Daily, Oral,10mg dapagliflozin in combination with Weekly, Subcutaneous, 35mg in 1mL solution REMD-477

Drug: Dapagliflozin 10 MG [Farxiga]; Drug: REMD-477

Treatment B

PLACEBO COMPARATOR

Daily, Oral,10mg dapagliflozin in combination with Weekly, Subcutaneous, 1mL solution Placebo

Drug: Dapagliflozin 10 MG [Farxiga]; Drug: Placebo

Interventions

Dapagliflozin 10 MG [Farxiga] DRUG

4-Week, double-blind, once daily oral 10mg dapagliflozin

Treatment A; Treatment B

REMD-477 DRUG

4-Week, double-blind, once weekly subcutaneous injection with 35mg REMD-477 in 1mL solution.

Treatment A

Placebo DRUG

4-Week, double-blind, once weekly subcutaneous injection with placebo in 1mL solution.

Treatment B

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 (\< 1u/kg per day) 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 ≤ 9 % 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 of T2DM, 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 run-in (visit 2)
• 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 Visit 1 or Visit 2
• Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
• Occurrence of symptomatic hypotension within 3 months prior to Visit 1 (Screen) or Visit 2
• Occurrence of multiple genital mycotic infections within 6 months prior to Visit 1 (Screen) or Visit 2
• Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to Visit 1 or Visit 2
• Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1
• Current signs and symptoms of anemia accompanied by a hemoglobin laboratory value at or below 10.0 g/dL at screening.
• Active eating disorders such as bulimia or anorexia nervosa
• 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;
• Treatment with systemic corticosteroids within 30 days of run-in (visit 2), or planned initiation of such therapy at Visit 1 or Visit 2. Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
• Medical history of bladder cancer or treatment for any cancer in the last five years prior to Visit 1. Resected basal cell carcinoma considered cured is exempted.

Sponsors & Collaborators

• University of California, San Diego: lead
• REMD Biotherapeutics, Inc.: collaborator
• Juvenile Diabetes Research Foundation: collaborator
• The Leona M. and Harry B. Helmsley Charitable Trust: 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

dapagliflozin; 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 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Single-center, randomized, double-blind, cross-over, multi-dose study.

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 11, 2020
• Study Start: February 22, 2021
• Primary Completion: February 28, 2022
• Study Completion: October 31, 2022
• Last Updated: January 23, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)