2026-525182-53-00RecruitingPhase 3
Zenagamtide use for the reduction of risk of major adverse cardiovascular events in people with established atherosclerotic cardiovascular disease and either overweight or obesity (AMBIENCE)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 320
- Locations
- 145
- Primary Endpoint
- Time from randomisation to first occurrence of a 4-P composite MACE endpoint consisting of: - CV death - Non-fatal MI - Non-fatal stroke - HF hospitalisationa or urgent HF visit
Study Overview
Brief Summary
To demonstrate superiority of zenagamtide once weekly versus placebo, both added to SoC on time to first MACE in participants with established ASCVD and either overweight or obesity.
Eligibility Criteria
- Ages
- 18 years to 64 years (18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Established ASCVD is defined as at least one of the below conditions (a-c): a. 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) < 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 T2D (at screening) are allowed in the study with the following provisions: a. Treatment should be stable for ≥ 90 days before screening as assessed by the investigator. b. Glucose lowering agents are permitted according to local label except GLP-1 RA, GIP and amylin analogues; for insulins, only basal insulin is allowed.
Exclusion Criteria
- •MI, stroke, unstable angina pectoris, or worsening 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 (CCI).
- •Chronic heart failure classified as (CCI) at screening. 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 1 question
- •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
- •Glycated haemoglobin (HbA1c) > 10% (86 mmol/mol) as measured by central laboratory at screening.
- •Treatment with any GLP-1 RA, GIP RA or amylin analogue for any indication within (CCI) before screening.
Arms & Interventions
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10143 (Drug)
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10145 (Drug)
Placebo (Zenagamtide)
Placebo
Intervention: Placebo (Zenagamtide) (Drug)
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10142 (Drug)
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10144 (Drug)
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10146 (Drug)
NNC0487-0111 B 10142, NNC0487-0111 B 10144, NNC0487-0111 B 10146, NNC0487-0111 B 10141, NNC0487-0111 B 10143, NNC0487-0111 B 10145
Test
Intervention: NNC0487-0111 B 10141 (Drug)
Outcomes
Primary Outcomes
Time from randomisation to first occurrence of a 4-P composite MACE endpoint consisting of: - CV death - Non-fatal MI - Non-fatal stroke - HF hospitalisationa or urgent HF visit
Time from randomisation to first occurrence of a 4-P composite MACE endpoint consisting of: - CV death - Non-fatal MI - Non-fatal stroke - HF hospitalisationa or urgent HF visit
Secondary Outcomes
- Time from randomisation to first occurrence of an expanded composite 5-P MACE endpoint consisting of: - All-cause death - Non-fatal MI - Non-fatal stroke - HF hospitalisationa or urgent HF visit - Coronary revascularization
- Time from randomisation to first occurrence of a composite 3-P MACE endpoint consisting of: - CV death - Non-fatal MI - Non-fatal stroke
- Change in eGFR (creatinine and cystatin C-based CKD-EPI 2021) for participants with baseline eGFR<60 mL/min/1.73 m2
- Time from randomisation to all-cause death
- Time from randomisation to CV death
- CCI
Investigators
EU Submission Hub
Scientific
Novo Nordisk A/S
Study Sites (145)
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