A Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus

NCT07160257 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 20250061
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the effect of maridebart cafraglutide relative to placebo on insulin sensitivity in participants with Type 2 Diabetes Mellitus (T2DM) treated with stable dose of metformin.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; T2DM; Maridebart Cafraglutide; AMG 133; Insulin sensitivity; β-cell Function

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in M-value from Hyperinsulinemic-euglycemic Clamp at Week 25

  Baseline and Week 25

Secondary Outcomes (38)

• Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events

  Up to Week 41

• Plasma Concentration of Maridebart Cafraglutide at Week 25

  Week 25

• Number of Participants with Anti-maridebart Cafraglutide Antibody Formation

  Up to Week 41

• Change from Baseline in Total Insulin Secretion at Week 25

  Baseline and Week 25

• Change from Baseline in First Phase Incremental ISR from Hyperglycemic Clamp (ISR0-8min) at Week 25

  Baseline and Week 25

Study Arms (2)

Maridebart cafraglutide

EXPERIMENTAL

Participants will receive maridebart cafraglutide subcutaneously (SC).

Drug: Maridebart cafraglutide

Placebo

PLACEBO COMPARATOR

Participants will receive placebo SC.

Drug: Placebo

Interventions

Maridebart cafraglutide DRUG

Maridebart cafraglutide will be administered SC.

Also known as: AMG 133

Maridebart cafraglutide

Placebo DRUG

Placebo will be administered SC.

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent before initiation of any study-specific activities/procedures.
• Male or female participants aged ≥ 18 and ≤ 70 years at the time of signing informed consent.
• Body mass index 27 ≥ and ≤ 45 kg/m\^2 at screening.
• Diagnosis of T2DM at least 6 months before screening based on the WHO classification.
• Treatment of T2DM for at least 3 months prior to screening with diet and exercise and a stable dose of metformin (either immediate release or extended release), with or without a stable dose of 1 additional OAM other than metformin.

You may not qualify if:

• Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other type of diabetes mellitus (except T2DM or history of gestational diabetes).
• History of proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment.
• One or more episodes of severe hypoglycemia (Level 3 hypoglycemia as defined by the American Diabetes Association classification criteria) within 6 months before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery.
• Has modified diet or adopted any nutritional lifestyle modifications within 3 months prior to screening, as assessed by the investigator (or designee) based on participant self-report.
• History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or breast ductal carcinoma in situ).
• Family (first-degree relative\[s\]) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).
• History or evidence of endocrine disorder (such as Cushing's syndrome) that can cause obesity.
• History or evidence of autoimmune disease that can directly or indirectly affect insulin production, insulin action, or glucose metabolism.
• History of any of the following within 90 days before screening: myocardial infarction, unstable angina, coronary artery bypass graft surgery or other major cardiovascular surgery, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure, or currently have New York Heart Association Class III or IV heart failure.
• History of chronic pancreatitis.
• History of acute pancreatitis within 6 months before screening.
• Positive human immunodeficiency virus test at screening.
• Evidence of hepatitis B or C infection.
• Estimated glomerular filtration rate \< 60 mL/min/1.73 m\^2 calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation at screening.
• Hemoglobin value \< 12 g/dL (males) or \< 10 g/dL (females) at screening or check-in (Day -4).

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

ProSciento, Inc. - Main Clinic

Chula Vista, California, 91911-1350, United States

RECRUITING

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Condition Hierarchy (Ancestors)

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

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: September 8, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): August 26, 2026
• Study Completion (Estimated): December 13, 2026
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (1)