Maridebart cafraglutide for improving insulin sensitivity and beta-cell function in people with type 2 diabetes

A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus

This trial will test whether maridebart cafraglutide can improve insulin sensitivity and beta-cell function in adults with type 2 diabetes who are on a stable dose of metformin.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Amgen (industry)
• Locations: 1 site (Chula Vista, California)
• Trial ID: NCT07160257 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study gives adults with type 2 diabetes who are on a stable dose of metformin either maridebart cafraglutide or a matching placebo to measure effects on insulin sensitivity and beta-cell function. Eligible participants must meet BMI and diabetes-duration criteria and may be on one additional oral diabetes medicine besides metformin. The primary comparison is the effect of drug versus placebo on insulin sensitivity using metabolic and physiologic testing. The study is sponsored by Amgen and conducted at a clinical research site in Chula Vista, California.

Who should consider this trial

Good fit: Adults aged 18–70 with type 2 diabetes diagnosed at least six months ago, BMI 27–45 kg/m^2, and on a stable dose of metformin (with or without one other oral glucose-lowering drug) are the intended participants.

Not a fit: People with type 1 diabetes, recent severe hypoglycemia or certain diabetic eye diseases, those outside the age or BMI ranges, or those not on stable metformin therapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, maridebart cafraglutide could improve insulin sensitivity and beta-cell function, which may lead to better blood glucose control for people with type 2 diabetes on metformin.

How similar studies have performed: Other incretin-based and GLP-1–related therapies have improved insulin sensitivity and glycemic control in prior studies, but maridebart cafraglutide itself is novel and is being tested in early-phase trials.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).
* Use within 90 days before randomization of medications, supplements, or alternative remedies for weight loss (eg, GLP-1RA, GIP agonists, phentermine/topiramate, naltrexone/bupropion, orlistat, and sympathomimetic drugs).
* Use within 90 days before randomization of chronic (\> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations).
* Use within 90 days before randomization of medications that may cause significant weight gain including, but not limited to, atypical antipsychotic and mood stabilizers.
* Current or prior use of herbal supplements that affect insulin or glucose within 30 days before randomization.
* Currently receiving treatment in another investigational device or drug study, or less than 30 days (or 5 half-lives, whichever is longer) since ending treatment on another investigational device or drug study(ies).
* Participants of childbearing potential unwilling to adhere to contraception requirements during treatment and for an additional 16 weeks after the last dose of IMP.
* Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of IMP.
* Participants planning to become pregnant while on study through 16 weeks after the last dose of IMP.
* Major surgical procedure planned during the study.
* Participant has known sensitivity to any of the products or components to be administered during dosing.
* Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
* History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or medical monitor, if consulted as necessary, would pose a risk to participant's safety or interfere with the study evaluation, procedures, or completion.

Where this trial is running

Chula Vista, California

• ProSciento, Inc. - Main Clinic — Chula Vista, California, United States (RECRUITING)

Study contacts

• Study coordinator: Amgen Call Center

Conditions: Type 2 Diabetes Mellitus, T2DM, Maridebart Cafraglutide, AMG 133, Insulin sensitivity, β-cell Function