Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in T2DM

NCT05093517 | Completed Early Phase 1 FDA Drug

• 1 other identifier: HSC20210463H
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

With REMD's glucagon receptor antagonist, the study team propose to provide a comprehensive examination of the effect of elevated plasma glucagon concentrations in Type 2 Diabetes Mellitus (T2D) patients on: (i) glucose tolerance; (ii) insulin sensitivity in liver, muscle, and adipocytes; (iii) beta cell function; (iv) adipocyte inflammation.

Conditions

Type 2 Diabetes; Glucose Tolerance Impaired; Insulin Sensitivity

Keywords

Fasting plasma glucagon; Glucagon receptor antagonist

Outcome Measures

Primary Outcomes (7)

• Glycated Hemoglobin (HbA1c)

  Change in HbA1c measured at baseline and after intervention administration

  Baseline to 13 weeks

• Fasting Plasma glucose (FPG)

  Change in fasting plasma glucose measured at baseline and after intervention administration

  Baseline to 13 weeks

• Plasma glucose (PG)

  Change in plasma PG measured at baseline and after intervention administration using an oral glucose tolerance test (OGTT)

  Baseline to 13 weeks

• Hepatic insulin sensitivity

  Change in hepatic glucose production (HGP)

  Baseline to 13 weeks

• Whole body glucose disposal

  Change in whole body glucose disposal measured in mg/kg/min

  Baseline to 13 weeks

• Plasma Free Fatty Acids (FFA)

  Change in plasma free fatty acids

  Baseline to 13 weeks

• Muscle Insulin sensitivity

  Change in muscle insulin sensitivity measured by insulin-stimulated glucose uptake during low dose high dose insulin clamp.

  Baseline to 13 weeks

Study Arms (2)

Glucagon Receptor Agonist (GRA) REMD-477 group

EXPERIMENTAL

Participants are assigned to a 12 week treatment of REMD-477

Drug: REMD-477

Placebo group

PLACEBO COMPARATOR

Participants are assigned to a 12 week course of placebo for REMD-477

Drug: Placebo Subcutaneous injection

Interventions

REMD-477 DRUG

A biologic glucagon receptor agonist to which randomized subjects are assigned 2:1

Glucagon Receptor Agonist (GRA) REMD-477 group

Placebo Subcutaneous injection DRUG

Placebo for REMD-477 to which subjects will be randomized 1:2.

Also known as: Placebo

Placebo group

Eligibility Criteria

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

You may qualify if:

• Type 2 diabetic subjects, males/females;
• age = 18-70 years
• BMI = 25-40 kg/m2;
• HbA1c = 7.5-10.0%;
• Type 2 Diabetics who are drug naïve or treated with metformin, sulfonylureas, SGLT-2 inhibitors or any combination thereof.
• Subjects must be on a stable dose of antidiabetic medications for at least 3 months prior to study.
• Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
• Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period

You may not qualify if:

• Subjects with a personal or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia, due to the potential increased of pancreatic alpha cell carcinogenicity associated with glucagon receptor antagonists.
• Subjects with a contraindication to MRI including artificial heart valves or pacemakers
• Patients with a known sensitivity to humanized antibodies
• Subjects treated with GLP-1 RAs or insulin are excluded.
• Subjects treated with a non-antidiabetic medication that may impact insulin sensitivity, such as systemic steroids, or lipase inhibitors (orlistat, Alli or Xenical)
• Hematocrit \< 34 vol%
• Serum creatinine \> 1.8 mg/dl
• AST (SGOT) \> 2 times upper limit of normal
• ALT (SGPT) \> 2 times upper limit of normal
• Any major organ system disease as identified by medical history, physical exam, and screening blood tests, EKG
• Subjects who cannot give written, voluntary consent
• Subjects with a major psychiatric disturbance
• Only subjects whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.
• Patients must not have type 1 diabetes
• Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c \> 10.0%

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Texas Diabetes Institute

San Antonio, Texas, 78207, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance; Insulin Resistance

Interventions

volagidemab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Hyperinsulinism

Study Officials

• Ralph DeFronzo, MD

  University of Texas Health San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded to the study drug or placebo randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized 2-arm placebo controlled trial

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 26, 2021
• Study Start: November 10, 2021
• Primary Completion: March 16, 2022
• Study Completion: March 16, 2022
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Once the study has completed enrollment and data analysis is complete, data will become available.

Locations

US (1)