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

Type 2 Diabetes Clinical Trial

Official title:

Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05093517
• Other study ID #: HSC20210463H
• Status: Suspended
• Phase: Early Phase 1
• Start date: November 10, 2021
• Est. completion date: November 2025

Study information

• Verified date: February 2024
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 24
• Est. completion date: November 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Glucose Tolerance Impaired
• Insulin Resistance
• Insulin Sensitivity
• Type 2 Diabetes

Intervention

Drug:
• REMD-477
A biologic glucagon receptor agonist to which randomized subjects are assigned 2:1
• Placebo Subcutaneous injection
Placebo for REMD-477 to which subjects will be randomized 1:2.

Locations

Country	Name	City	State
United States	Texas Diabetes Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycated Hemoglobin (HbA1c)	Change in HbA1c measured at baseline and after intervention administration	Baseline to 13 weeks
Primary	Fasting Plasma glucose (FPG)	Change in fasting plasma glucose measured at baseline and after intervention administration	Baseline to 13 weeks
Primary	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
Primary	Hepatic insulin sensitivity	Change in hepatic glucose production (HGP)	Baseline to 13 weeks
Primary	Whole body glucose disposal	Change in whole body glucose disposal measured in mg/kg/min	Baseline to 13 weeks
Primary	Plasma Free Fatty Acids (FFA)	Change in plasma free fatty acids	Baseline to 13 weeks
Primary	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