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

NCT ID: NCT05093517

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-10
• Study Completion Date: 2022-03-16

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.

Detailed Description

Subjects with T2DM inadequately controlled on current medications will participate in a glucose tolerance test, euglycemic insulin clamp combined with 3-3H-glucose and 14-C glycerol infusion, adipose tissue biopsy, before and 12 weeks after treatment with REMD 477 or placebo.

Conditions

Type 2 Diabetes; Glucose Tolerance Impaired; Insulin Sensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Glucagon Receptor Agonist (GRA) REMD-477 group

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

Group Type: EXPERIMENTAL

REMD-477

Intervention Type: DRUG

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

Placebo group

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

Group Type: PLACEBO_COMPARATOR

Placebo Subcutaneous injection

Intervention Type: DRUG

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

Interventions

REMD-477

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

Intervention Type: DRUG

Placebo Subcutaneous injection

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

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

Inclusion Criteria

1. Type 2 diabetic subjects, males/females;

2. age = 18-70 years

3. BMI = 25-40 kg/m2;

4. HbA1c = 7.5-10.0%;

5. Type 2 Diabetics who are drug naïve or treated with metformin, sulfonylureas, SGLT-2 inhibitors or any combination thereof.

6. Subjects must be on a stable dose of antidiabetic medications for at least 3 months prior to study.

7. Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

8. 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

Exclusion Criteria

1. 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.

2. Subjects with a contraindication to MRI including artificial heart valves or pacemakers

3. Patients with a known sensitivity to humanized antibodies

4. Subjects treated with GLP-1 RAs or insulin are excluded.

5. Subjects treated with a non-antidiabetic medication that may impact insulin sensitivity, such as systemic steroids, or lipase inhibitors (orlistat, Alli or Xenical)

6. Hematocrit < 34 vol%

7. Serum creatinine > 1.8 mg/dl

8. AST (SGOT) > 2 times upper limit of normal

9. ALT (SGPT) > 2 times upper limit of normal

10. Any major organ system disease as identified by medical history, physical exam, and screening blood tests, EKG

11. Subjects who cannot give written, voluntary consent

12. Subjects with a major psychiatric disturbance

13. Only subjects whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.

14. Patients must not have type 1 diabetes

15. Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c > 10.0%

16. Patients must not have received a thiazolidinedione, GLP-1 agonist, or insulin for more than one week during the year prior to randomization

17. Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.

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

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph DeFronzo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health San Antonio

Locations

Texas Diabetes Institute

San Antonio, Texas, United States

Countries

United States

Other Identifiers

HSC20210463H

Identifier Type: -

Identifier Source: org_study_id