Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

9 Jun 2025 → ongoing

Decision date (initial)

2025-06-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-515523-11-00

WHO UTN

U1111-1317-0255

ClinicalTrials.gov

NCT06858878

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To demonstrate that maridebart cafraglutide mg is superior to placebo for percent change in body weight

Secondary objectives 7

1. (controlled for Type 1 error) To demonstrate that maridebart cafraglutide mg is superior to placebo for: Reduction in central adiposity Reduction in body weight
2. (controlled for Type I error) To demonstrate that maridebart cafraglutide mg is superior to placebo for: Reduction in systolic blood pressure (SBP) Reduction in triglycerides Improvement in glycemic control Improvement in functional health and well-being
3. (Not controlled for Type I error) To demonstrate that maridebart cafraglutide mg is superior to placebo for: Reduction in body weight Improvement in glycemic control Improvement in cardiovascular risk factors
4. (Not controlled for Type I error) To demonstrate that maridebart cafraglutide mg is superior to placebo for: Improvement in lipid parameters Improvement in diastolic blood pressure (DBP)
5. (Not controlled for Type I error) To demonstrate that maridebart cafraglutide mg is superior to placebo for the improvement in functional health and well-being
6. (Not controlled for Type I error) To characterize the safety and tolerability of maridebart cafraglutide
7. (Not controlled for Type I error) To characterize the pharmacokinetics (PK) of maridebart cafraglutide

Conditions and MedDRA coding

Chronic Weight Management

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003439-PIP02-23

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 8

1. Participant has provided informed consent before initiation of any study-specific activities/procedures.
2. Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
3. BMI ≥ 27 kg/m2 at screening
4. History of at least 1 self-reported unsuccessful attempt at weight loss by diet and exercise,History of at least 1 self-reported unsuccessful attempt at weight loss by diet and exercise,
5. Diagnosis of T2DM at least 180 days before screening, based on the World Health Organization (WHO) classification.
6. Hemogloblin A1c ≥ 7.0% (53 mmol/mol) and ≤ 10.0% (86 mmol/mol) at screening.
7. Treatment of T2DM with diet and exercise alone and/or with a stable treatment of up to 3 oral glucose-lowering medications (as per local labeling), for at least 90 days before screening, except dipeptidyl peptidase 4 (DPP-4) inhibitors, and GLP-1RAs.
8. In the opinion of the investigator, well-motivated and willing to: Follow study procedures for the duration of the study, including, but not limited to, following lifestyle advice, maintaining a study log(s)/diary(ies), and completing required study visits and, questionnaires. Perform self-monitoring of blood glucose (SMBG) per protocol

Exclusion criteria 42

1. Obesity induced by other endocrinologic disorders (including, but not limited to Cushing’s syndrome), or monogenetic or syndromic forms of obesity (including, but not limited to Prader Willi syndrome and melanocortin-4 receptor deficiency).
2. One or more episode of severe hypoglycemia (Level 3 hypoglycemia) within 180 days before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery. Refer to Section 11.9 (Appendix 9) for additional information.
3. History of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms.
4. History of a hematological condition (such as hemolytic anemia, sickle cell disease) that may interfere with HbA1c measurement.
5. Fasting plasma glucose > 270 mg/dL (15.0 mmol/L) at screening.
6. 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).
7. Use within 90 days before randomization or likely in the opinion of the investigator to require use during the study of medications that may cause significant weight gain (including, but not limited to chronic systemic glucocorticoid therapy, tricyclic antidepressants, atypical antipsychotics, valproic acid, and lithium). Note: Selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) are permitted.
8. Currently receiving treatment in another investigational device or drug study, or less than 90 days (or 5 half-lives, whichever is longer) since ending treatment on another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies.
9. Previous participation in a study that includes maridebart cafraglutide (AMG 133) or AMG 598.
10. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation or receiving dialysis at screening.
11. Calcitonin ≥ 50 ng/L (pg/mL) at screening.
12. History of organ transplant (except for corneal transplant) or on transplant list.
13. Thyroid-stimulating hormone (TSH) < 0.4 mIU/L or TSH > 6.0 mIU/L with free thyroxine below the lower limit of normal at screening. Participants who receive treatment for hypothyroidism are permitted in the study, if their thyroid hormone replacement dose has been stable for at least 90 days before randomization and their TSH at screening is not exclusionary.
14. Acute or chronic hepatitis, signs, and symptoms of any liver disease other than MASLD, alanine aminotransferase (ALT) > 3.0 x the upper limit of normal (ULN), or total bilirubin (TBL) > 1.2 x ULN (except for known diagnosis of Gilbert syndrome, which is not exclusionary).
15. Systolic blood pressure > 180 mmHg and/or DBP >120 mmHg at screening.
16. History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or prostate cancer in situ).
17. Patient Health Questionnaire-9 (PHQ-9) score of > 15 on day 1 before randomization
18. Any suicidal ideation of category 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline version at screening, or on the C-SSRS Since Last Visit version on day 1 before randomization
19. Lifetime history of suicide attempt evaluated through C-SSRS Baseline version at screening or any suicidal behavior on the C-SSRS Since Last Visit version on day 1 before randomization.
20. History of chronic pancreatitis.
21. History of acute pancreatitis within 180 days before screening.
22. Family (first-degree relative(s) or personal history of MTC or multiple endocrine neoplasia syndrome type 2.
23. 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.
24. History of any of the following within 60 days before screening: myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack.
25. New York Heart Association Class IV heart failure.
26. History of unstable major depressive disorder (MDD) or other severe psychiatric disorder within 2 years before screening. Participants with MDD or other psychiatric disorder whose disease state is considered stable for the past 2 years before screening and is expected to remain stable throughout the study, in the opinion of the investigator, may be eligible.
27. Participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 16 weeks after the last dose of investigational product. Refer to Section 11.5 (Appendix 5) for additional contraceptive information
28. Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of investigational product.
29. Participants planning to become pregnant while on study through 16 weeks after the last dose of investigational product.
30. Participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 before randomization
31. Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator’s opinion, might jeopardize the participant’s safety or compliance with the protocol.
32. Major surgical procedure planned during the study. Participants with minor surgical procedures (not requiring general anesthesia or deep sedation) planned during the study may be eligible at the discretion of the investigator
33. Investigative site personnel directly affiliated with the study and/or their immediate family (ie, spouse, parent, child, or sibling, whether biological or legally adopted).
34. Self-reported change in body weight > 5 kg within 90 days before screening.
35. Participant has known sensitivity to any of the products or components to be administered during dosing.
36. Clinically significant gastric-emptying abnormality (including, but not limited to gastroparesis and gastric outlet obstruction).
37. Previous or planned (during the study) surgical, endoscopic, or device-based treatment for obesity. The following are allowed: liposuction and/or abdominoplasty that was performed > 1 year before screening; laparoscopic adjustable gastric banding, intragastric balloon, and/or duodenal-jejunal bypass liner or sleeves if removed > 1 year before screening.
38. Type 1 diabetes mellitus, or any other types of diabetes mellitus (except T2DM or history of gestational diabetes).
39. Current or prior treatment (within 90 days before screening) with DPP-4 inhibitors, oral GLP-1RAs, or any injectable therapy for T2DM.
40. Proliferative diabetic retinopathy OR diabetic macular edema OR non-proliferative diabetic retinopathy that requires acute treatment. Note: A dilated fundoscopic examination or digital fundus photography with specified camera for non-dilated examination, performed by an ophthalmologist or another suitably qualified healthcare provider (eg, optometrist) within the past 90 days before screening or in the period between screening and randomization is required to verify eligibility criteria.
41. Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema (for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor [VEGF] inhibitors). History of proliferative diabetic retinopathy, diabetic maculopathy OR severe non-proliferative diabetic retinopathy. Note: A dilated fundoscopic examination or digital fundus photography with specified camera for non-dilated examination, performed by an ophthalmologist or another suitably qualified healthcare provider (eg, optometrist) within the past 90 days before screening or in the period between screening and randomization is required to verify eligibility criteria.
42. Use within 90 days before randomization or likely in the opinion of the investigator to require use during the trial of medications that may cause significant weight gain (including, but not limited to chronic (>14 days) systemic glucocorticoid therapy (topical, intraocular, intranasal, intraarticular, or inhaled preparations are allowed), atypical tricyclic antidepressants, atypical antipsychotics, llithium and all formulations of valproic acid). Note: Selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) are permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in body weight at week 72

Secondary endpoints 10

1. Change from baseline in waist circumference (cm) at week 72
2. Achieving ≥ 5% reduction in body weight from baseline at week 72
3. Achieving ≥ 10% reduction in body weight from baseline at week 72
4. Achieving ≥ 15% reduction in body weight from baseline at week 72
5. Change from baseline in SBP (mmHg) at week 72
6. Percent change from baseline in fasting triglycerides at week 72
7. Change from baseline in fasting plasma glucose (mg/dL) at week 72
8. Change from baseline in hemoglobin A1c (HbA1c) (%, mmol/mol) at week 72
9. Achieving HbA1c < 7% at week 72
10. Change from baseline in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at week 72

Investigational products

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

Test 1

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 6

Locations

6 EU/EEA countries · 68 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 94 files

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

Application history

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