MARIDEBART CAFRAGLUTIDE for Atherosclerotic cardiovascular disease | Obesity

Stratification factors

• Diabetes status (with type 2 diabetes mellitus [T2DM] vs without T2DM)
• Region (Latin America; Asia; Eastern Europe; Western Europe + Australia; United States + Canada)

Inclusion criteria

• {"criterion_text":"- Participant has provided informed consent before initiation of any study-specific activities/procedures."}
• {"criterion_text":"- Age ≥ 45 years at screening."}
• {"criterion_text":"- BMI of ≥ 27 kg/m2 at screening."}
• {"criterion_text":"- 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

• {"criterion_text":"- 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)"}
• {"criterion_text":"- Use within 90 days before randomization of medications that may cause significant weight gain in the judgement of the investigator."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Previous or ongoing participation in a study that includes maridebart cafraglutide or AMG 598"}
• {"criterion_text":"- Participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 before randomization."}
• {"criterion_text":"- Planned bariatric surgery known at the time of screening, or performed within 180 days before screening."}
• {"criterion_text":"- Calcitonin ≥ 50 ng/L (pg/mL) at screening."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Clinically significant gastric emptying abnormality (including, but not limited to gastroparesis and gastric outlet obstruction)."}
• {"criterion_text":"- Planned (during the study) coronary, carotid, or peripheral artery revascularization known at prior to randomization"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History of chronic pancreatitis."}
• {"criterion_text":"- History of acute pancreatitis in the 180 days before screening or between screening and randomization."}
• {"criterion_text":"- Family (first-degree relative[s]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Lifetime history of suicide attempt"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- A history of ischemic optic neurophathy"}
• {"criterion_text":"- Obesity induced by specific endocrinologic disorders, or monogenetic or syndromic forms of obesity."}
• {"criterion_text":"- Severe, concomitant disease that is expected to reduce life expectancy to < 2 years."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Use within 90 days before randomization of medications prescribed for weight loss."}

Primary endpoints

• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Time to first occurrence (time-to-event composite endpoint of CV death, MI, or ischemic stroke)."}
• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Time to first occurrence (time-to-event composite endpoint of all-cause death, MI, ischemic stroke, coronary revascularization, or HF event)."}

Secondary endpoints

• {"endpoint_text":"- Time to first occurrence of a composite endpoint consisting of: CV death, MI, ischemic stroke, or HF event","definition_or_measurement_approach":"Time to first occurrence (time-to-event composite endpoint)."}
• {"endpoint_text":"- Time to first occurrence of a composite endpoint consisting of: CV death, MI, ischemic stroke or coronary revascularization","definition_or_measurement_approach":"Time to first occurrence (time-to-event composite endpoint)."}

Methods

• Digital pre-consent and digital recruitment materials (K2 digital pre-consent materials / Digital Pre-Consent Information documents referenced in recruitment materials).
• Physician referral letters (K2 recruitment physician referral letters provided for multiple countries).
• Patient brochures and pre-enrolment information cards (K2 patient brochure / pre-enrollment card documents).
• Online advertisements and website recruitment (advertisement text, website and Meta ad materials referenced in recruitment documents).
• Antidote Technologies patient-matching and outreach (Antidote Technologies Limited listed in sponsor third parties with contact hello@antidote.me).
• CRO / vendor-supported recruitment and site-to-patient services (e.g., MARKEN Germany site-to-patient (STP) activity; IQVIA Study Hub and retention services).
• Country/site-specific recruitment packs and procedures (K1 recruitment procedures and localized materials provided for multiple Member States).

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Study Hub, eCOA, retention, monitoring services in Denmark

Name

Excelya Greece CRO Single Member S.A.

Responsibilities

Submission activities in Greece

Name

Medidata Solutions Inc.

Responsibilities

Provision of data management/eCOA/study platform services (sponsor duties code 7 indicated)

Third parties

• {"country":"United Kingdom","full_name":"Antidote Technologies Limited","duties_or_roles":"[{\"id\":1022206,\"code\":\"2\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"[{\"id\":1022211,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"[{\"id\":1022213,\"code\":\"15\",\"value\":\"Study Hub, eCOA, retention, monitoring services in Denmark\"},{\"id\":1022214,\"code\":\"7\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"[{\"id\":1022205,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"[{\"id\":1022207,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"The Brigham And Women’s Hospital Inc.","duties_or_roles":"[{\"id\":1022202,\"code\":\"15\",\"value\":\"Adjudication\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"[{\"id\":1022204,\"code\":\"7\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"[{\"id\":1022203,\"code\":\"4\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"Excelya Greece CRO Single Member S.A.","duties_or_roles":"[{\"id\":1022209,\"code\":\"1\"},{\"id\":1022210,\"code\":\"15\",\"value\":\"Submission activities in Greece\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"[{\"id\":1022208,\"code\":\"15\",\"value\":\"Site to patient (STP)\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"[{\"id\":1022212,\"code\":\"3\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Antidote Technologies Limited (additional address entry)","duties_or_roles":"[{\"id\":1022206,\"code\":\"2\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}