MARIDEBART CAFRAGLUTIDE for Type 2 diabetes mellitus | Obesity | Overweight

Stratification factors

• sex assigned at birth (female, male)
• background T2DM treatment

Inclusion criteria

• {"criterion_text":"- Participant has provided informed consent before initiation of any study-specific activities/procedures.\n- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).\n- BMI ≥ 27 kg/m2 at screening\n- 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,\n- Diagnosis of T2DM at least 180 days before screening, based on the World Health Organization (WHO) classification.\n- Hemogloblin A1c ≥ 7.0% (53 mmol/mol) and ≤ 10.0% (86 mmol/mol) at screening.\n- 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.\n- 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

• {"criterion_text":"- 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).\n- 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.\n- Calcitonin ≥ 50 ng/L (pg/mL) at screening.\n- History of organ transplant (except for corneal transplant) or on transplant list.\n- 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.\n- 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).\n- Systolic blood pressure > 180 mmHg and/or DBP >120 mmHg at screening.\n- History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or prostate cancer in situ).\n- Patient Health Questionnaire-9 (PHQ-9) score of > 15 on day 1 before randomization\n- 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\n- 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.\n- 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.\n- History of chronic pancreatitis.\n- History of acute pancreatitis within 180 days before screening.\n- Family (first-degree relative(s) or personal history of MTC or multiple endocrine neoplasia syndrome type 2.\n- 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.\n- 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.\n- New York Heart Association Class IV heart failure.\n- 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.\n- 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\n- Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of investigational product.\n- Participants planning to become pregnant while on study through 16 weeks after the last dose of investigational product.\n- History of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms.\n- Participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 before randomization\n- 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.\n- 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\n- Investigative site personnel directly affiliated with the study and/or their immediate family (ie, spouse, parent, child, or sibling, whether biological or legally adopted).\n- Self-reported change in body weight > 5 kg within 90 days before screening.\n- Participant has known sensitivity to any of the products or components to be administered during dosing.\n- Clinically significant gastric-emptying abnormality (including, but not limited to gastroparesis and gastric outlet obstruction).\n- 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.\n- Type 1 diabetes mellitus, or any other types of diabetes mellitus (except T2DM or history of gestational diabetes).\n- Current or prior treatment (within 90 days before screening) with DPP-4 inhibitors, oral GLP-1RAs, or any injectable therapy for T2DM.\n- History of a hematological condition (such as hemolytic anemia, sickle cell disease) that may interfere with HbA1c measurement.\n- 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.\n- 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.\n- 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.\n- Fasting plasma glucose > 270 mg/dL (15.0 mmol/L) at screening.\n- 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).\n- 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.\n- 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.\n- Previous participation in a study that includes maridebart cafraglutide (AMG 133) or AMG 598."}

Primary endpoints

• {"endpoint_text":"- Percent change from baseline in body weight at week 72","definition_or_measurement_approach":"Percent change from baseline in measured body weight at Week 72 (comparison of weight at Week 72 versus baseline)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in waist circumference (cm) at week 72","definition_or_measurement_approach":"Change from baseline in measured waist circumference (cm) at Week 72."}
• {"endpoint_text":"- Achieving ≥ 5% reduction in body weight from baseline at week 72","definition_or_measurement_approach":"Proportion of participants with ≥5% reduction in body weight from baseline at Week 72."}
• {"endpoint_text":"- Achieving ≥ 10% reduction in body weight from baseline at week 72","definition_or_measurement_approach":"Proportion of participants with ≥10% reduction in body weight from baseline at Week 72."}
• {"endpoint_text":"- Achieving ≥ 15% reduction in body weight from baseline at week 72","definition_or_measurement_approach":"Proportion of participants with ≥15% reduction in body weight from baseline at Week 72."}
• {"endpoint_text":"- Change from baseline in SBP (mmHg) at week 72","definition_or_measurement_approach":"Change from baseline in systolic blood pressure (mmHg) at Week 72."}
• {"endpoint_text":"- Percent change from baseline in fasting triglycerides at week 72","definition_or_measurement_approach":"Percent change from baseline in fasting triglyceride level at Week 72."}
• {"endpoint_text":"- Change from baseline in fasting plasma glucose (mg/dL) at week 72","definition_or_measurement_approach":"Change from baseline in fasting plasma glucose (mg/dL) at Week 72."}
• {"endpoint_text":"- Change from baseline in hemoglobin A1c (HbA1c) (%, mmol/mol) at week 72","definition_or_measurement_approach":"Change from baseline in HbA1c (percentage and mmol/mol) at Week 72."}
• {"endpoint_text":"- Achieving HbA1c < 7% at week 72","definition_or_measurement_approach":"Proportion of participants achieving HbA1c < 7% at Week 72."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change from baseline in the IWQOL-Lite-CT Physical Function composite score at Week 72 (patient-reported outcome measure)."}

Methods

• Physician referral letters / Dr-to-Patient letters (country-specific materials submitted).
• Patient brochures and study information leaflets (K2 Patient Brochure, About Clinical Studies Brochure).
• Pre-enrollment cards / Study pre-enrolment information cards.
• Study pre-consent information documents and site-specific pre-consent materials.
• GP / primary care letters (country-specific GP/physician outreach materials).
• Site-specific recruitment texts and signage (documents include site recruitment texts for Germany).
• Subject information and informed consent forms provided in multiple languages (used as recruitment/information material).

Italy

Earliest CTIS Part Ii Submission Date

15-05-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

279

Number Of Sites

7

Number Of Participants

8

Bulgaria

Earliest CTIS Part Ii Submission Date

20-05-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

274

Number Of Sites

6

Number Of Participants

30

Poland

Earliest CTIS Part Ii Submission Date

14-05-2025

Latest Decision Or Authorization Date

22-02-2026

Processing Time Days

284

Number Of Sites

12

Number Of Participants

156

Hungary

Earliest CTIS Part Ii Submission Date

15-05-2025

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

281

Number Of Sites

13

Number Of Participants

97

Czechia

Earliest CTIS Part Ii Submission Date

06-05-2025

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

287

Number Of Sites

11

Number Of Participants

49

Germany

Earliest CTIS Part Ii Submission Date

12-05-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

332

Number Of Sites

20

Number Of Participants

80

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Suvoda LLC

Responsibilities

Sponsor duty code 3 (as listed in CTIS thirdParty entry)

Name

Medidata Solutions Inc.

Responsibilities

Sponsor duty code 7 (as listed in CTIS thirdParty entry)

Name

IQVIA Limited

Responsibilities

Recruitment and Retention, eCOA, DCT, eConsent, ABPM, Monitoring, Optional Dietician resource

Name

Altasciences Compagnie Inc.

Responsibilities

Sponsor duty code 4 (as listed in CTIS thirdParty entry)

Name

Bioagilytix Labs LLC

Responsibilities

Sponsor duty code 4 (as listed in CTIS thirdParty entry)

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Sponsor duty code 4 (as listed in CTIS thirdParty entry)

Third parties

• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Recruitment and Retention, eCOA, DCT, eConsent, ABPM, Monitoring, Optional Dietician resource","organisation_type":"Pharmaceutical company"}