Cardiovascular Risk, Obesity
Conditions
Brief summary
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
DRUGZenagamtide
Zenagamtide will be administered subcutaneously.
DRUGPlacebo
Placebo will be administered subcutaneously.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
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) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From baseline (week 0) to up to 203 weeks or longer | Measured in days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From baseline (week 0) to up to 203 weeks or longer | 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 | From baseline (week 0) to up to 203 weeks or longer | 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) | From baseline (week 0) to week 104 | Measured as mL/min/1.73 m\^2. |
| Time from randomization to all-cause death | From baseline (week 0) to up to 203 weeks or longer | Measured in days. |
| Time from randomization to CV death | From baseline (week 0) to up to 203 weeks or longer | Measured in days. |
Countries
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, United States
Contacts
CONTACTNovo Nordisk
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed