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

Short name AMBIENCE

NCTNCT07861100Other idNN9490-8037Other idU1111-1335-0048Other id2026-525182-53

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Not yet recruiting
Phase: Phase 3
Enrollment: 8,500 participants (estimated)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 26 countries
United States, Argentina, Australia, Brazil, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Greece, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, South Africa, South Korea, Spain, Turkey (Türkiye), United Kingdom
Start: 26 Oct 2026 (estimated)
Primary completion: 16 Sept 2030 (estimated)
Completion: 16 Sept 2030 (estimated)
First posted: 6 Oct 2026
Last update posted: 6 Oct 2026
Conditions: Cardiovascular Risk · Obesity

Timeline

1 trial · 1 not yet recruiting

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

202620272028202920302031

Ph 3
AMBIENCE
NCT07861100
est. 26 Oct 2026 to est. 16 Sept 2030

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This clinical study is being conducted to evaluate the safety and effectiveness of zenagamtide in people with atherosclerotic cardiovascular disease (ASCVD) and excess body weight compared with placebo. The purpose of this clinical study is to find out if zenagamtide is safe and effective for treating people who have ASCVD and excess body weight. Participants will be randomly assigned by chance to receive either zenagamtide, the investigational treatment being tested, or a placebo, which contains no active medicine. Half of the participants will receive zenagamtide, and treatment assignment will be determined randomly. Zenagamtide is a new investigational medicine that is not yet available for prescription by doctors.

Interventions

ZenagamtideDrug
PlaceboDrug

Arms2

Experimental
Zenagamtide
Participants will receive zenagamtide subcutaneously (s.c.) in a dose escalating manner once weekly.
Placebo comparator
Placebo
Participants will receive placebo matched to zenagamtide s.c. once weekly.

Primary outcomes1

Outcomes the sponsor listed as primary.

Time from randomization to first occurrence of a 4-point (P) composite major adverse cardiovascular events (MACE) endpoint consisting of: Cardiovascular (CV) death, Non-fatal MI, Non-fatal stroke, HF hospitalization or urgent HF visit
Time frame · From baseline (week 0) to up to 203 weeks or longer
Registry description
Measured in days.

Secondary outcomes(5)

Time from randomization to first occurrence of an expanded 5-P composite MACE endpoint consisting of: All-cause death, Non-fatal MI, Non-fatal stroke, HF hospitalization or urgent HF visit, Coronary revascularization
Time frame · From baseline (week 0) to up to 203 weeks or longer
Registry description
Measured in days.
Time from randomization to first occurrence of a 3-P composite MACE endpoint consisting of: CV death, Non-fatal MI, Non-fatal stroke
Time frame · From baseline (week 0) to up to 203 weeks or longer
Registry description
Measured in days.
Change in Estimated Glomerular Filtration Rate (eGFR) (creatinine and cystatin C-based Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021) for participants with baseline eGFR< 60 millilitre per minute per 1.73 square metre (mL/min/1.73 m^2)
Time frame · From baseline (week 0) to week 104
Registry description
Measured as mL/min/1.73 m\^2.
Time from randomization to all-cause death
Time frame · From baseline (week 0) to up to 203 weeks or longer
Registry description
Measured in days.
Time from randomization to CV death
Time frame · From baseline (week 0) to up to 203 weeks or longer
Registry description
Measured in days.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 45 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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) 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: 1. Treatment should be stable for greater than or equal to (≥) 90 days before screening as assessed by the investigator. 2. 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. Exclusion Criteria: * 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. * Chronic heart failure classified at screening. * Glycaemia-related: 1. Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator. 2. Known history of hypoglycaemia unawareness as indicated by the investigator according to Clarke's questionnaire question 8. 3. History of type 1 diabetes (T1D). 4. 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. 5. Glycated haemoglobin (HbA1c) greater than (\>) 10 percentage (%) (86 millimoles per mole \[mmol/mol\]) as measured by central laboratory at screening. * General health and safety: 1. Treatment with any GLP-1 RA, GIP RA or amylin analogue for any indication before screening.

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