Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants with Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

10 Oct 2025 → ongoing

Decision date (initial)

2025-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-516652-18-00

WHO UTN

U1111-1320-5229

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality (dual primary endpoints)

Secondary objectives 2

1. To demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing the incidence of 3-P MACE or HF events
2. To demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing the incidence of 3-P MACE or coronary revascularization

Conditions and MedDRA coding

Atherosclerotic cardiovascular disease (ASCVD) and obesity or overweight

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000023-PIP97-53

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request. Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available on the Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participant has provided informed consent before initiation of any study-specific activities/procedures.
2. Age ≥ 45 years at screening.
3. BMI of ≥ 27 kg/m2 at screening.
4. History of ASCVD with a documented history of at least one of the following: - Prior MI (presumed atherothrombiotic event due to plaque rupture/erosion) - Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation) - Symptomatic PAD, as evidenced by intermittent claudication with ABI < 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease

Exclusion criteria 30

1. History of any of the following within 60 days before screening, or between screening and randomization: Myocardial infarction (MI), hospitalization for unstable angina, arterial revascularization (eg coronory, cerebrovascular or peripheral), major cardiovascular surgery, stroke, or transient ischemic attack (TIA)
2. History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
3. History of organ transplant (except for corneal transplant), on transplant list, or anticipated to receive chronic mechanical circulatory support or heart transplantation within 12 months from randomization.
4. Obesity induced by specific endocrinologic disorders, or monogenetic or syndromic forms of obesity.
5. Severe, concomitant disease that is expected to reduce life expectancy to < 2 years.
6. Any disorder, unwillingness, or inability not covered by any of the other exclusioncriteria, which in the investigator’s opinion, might jeopardize the participant’s safety or compliance with the protocol.
7. Use of any GLP-1 RA, GIP agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the study.
8. Treatment with continuous SC insulin therapy (insulin pump) during screening or participants on intensive (basal-bolus) insulin therapy guided by carbohydrate counting, defined as an individualized insulin dosing regimen that adjusts pre-meal bolus insulin doses based on estimated carbohydrate content of meals and current blood glucose levels.
9. Use within 90 days before randomization of medications prescribed for weight loss.
10. Use within 90 days before randomization of medications that may cause significant weight gain in the judgement of the investigator.
11. Currently receiving treatment in another investigational device or drug study, or less than 90 days (or 5 half-lives, whichever is longer) prior to randomization since ending treatment in another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies.
12. For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening): - HbA1c > 10.0% (86 mmol/mol) at screening - Uncontrolled diabetes requiring immediate therapy at randomization in the judgement of the investigator - History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization - One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness - History of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy ,or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema (for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors).
13. Previous or ongoing participation in a study that includes maridebart cafraglutide or AMG 598
14. Participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 before randomization.
15. Planned bariatric surgery known at the time of screening, or performed within 180 days before screening.
16. Calcitonin ≥ 50 ng/L (pg/mL) at screening.
17. Acute or chronic hepatitis, signs, and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) > 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) > 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
18. Clinically significant gastric emptying abnormality (including, but not limited to gastroparesis and gastric outlet obstruction).
19. Planned (during the study) coronary, carotid, or peripheral artery revascularization known at prior to randomization
20. New York Heart Association (NYHA) class IV HF during screening or hospitalization for heart failure (HF) within 60 days before screening or between screening and randomization.
21. Type 1 diabetes mellitus, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
22. History of any other condition (including, but not limited to known drug or alcohol abuse and eating disorders) that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the study.
23. History of chronic pancreatitis.
24. History of acute pancreatitis in the 180 days before screening or between screening and randomization.
25. Family (first-degree relative[s]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
26. Estimated Glomerular Filtration Rate (eGFR) < 20 mL/min/1.73m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation or receiving dialysis at screening.
27. History of unstable major depressive disorder (MDD) or other severe psychiatric disorder within 2 years before screening or between screening and randomization. - Participants with MDD or other psychiatric disorder whose disease state is considered stable for the past 2 years before screening and are expected to remain stable throughout the study, in the opinion of the investigator, may be eligible
28. History of non-suicidal self-injury (NSSI) within 5 years before screening or between screening and randomization. NSSI is a self-inflicted injury that causes pain or superficial damage (eg, cutting, carving, or burning of the skin) as a way to cope with emotional pain, sadness, anger and stress and is not intended to cause death.
29. Lifetime history of suicide attempt
30. A history of ischemic optic neurophathy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Time to first occurrence of a composite endpoint consisting of: CV death, myocardial infarction (MI), or ischemic stroke (3-point major adverse cardiac events [3-P MACE])
2. Time to first occurrence of a composite endpoint consisting of: all-cause death, MI, ischemic stroke, coronary revascularization, or heart failure (HF) event (5-point major adverse cardiac events [5-P MACE])

Secondary endpoints 2

1. Time to first occurrence of a composite endpoint consisting of: CV death, MI, ischemic stroke, or HF event
2. Time to first occurrence of a composite endpoint consisting of: CV death, MI, ischemic stroke or coronary revascularization

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 11

Locations

18 EU/EEA countries · 366 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 312 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications