A Research Study to Look at How Well Zenagamtide Works Compared to Placebo in People With Established Atherosclerotic Cardiovascular Disease and Either Overweight or Obesity

Prior treatment

• MI, stroke, unstable angina pectoris, or worsening heart failure (HF) leading to either hospitalization or intravenous loop diuretics within 30 days prior to the day of screening and until randomization.
• Coronary, carotid, or peripheral artery revascularization or percutaneous valve repair or replacement within 30 days prior to the day of screening or planned during the study period and known at screening.
• General health and safety:
  • Treatment with any GLP-1 RA, GIP RA or amylin analogue for any indication before screening.

Other illness

• Chronic heart failure classified at screening.

Lab values

• Glycaemia-related:
  • Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.
  • Known history of hypoglycaemia unawareness as indicated by the investigator according to Clarke's questionnaire question 8.
  • History of type 1 diabetes (T1D).
  • Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) within 180 days before screening or who, at the time of screening, are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
  • Glycated haemoglobin (HbA1c) greater than (\>) 10 percentage (%) (86 millimoles per mole \[mmol/mol\]) as measured by central laboratory at screening.

• Established ASCVD is defined as at least one of the below conditions (a-c):
  • Prior myocardial infarction (MI) b. Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an ankle-brachial index (ABI) less than (\<) 0.85 at rest ii. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis) c. Cerebrovascular disease defined as the following: i. Prior stroke
• Participants with Type 2 Diabetes (T2D) (at screening) are allowed in the study with the following provisions:
  • Treatment should be stable for greater than or equal to (≥) 90 days before screening as assessed by the investigator.
  • Glucose lowering agents are permitted according to local label except glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) and amylin analogues; for insulins, only basal insulin is allowed.