Cardiovascular Disease
Conditions
Brief summary
This study will look at the effects of CagriSema on cardiovascular events (for example heart attack and stroke) in people living with cardiovascular disease. Participants will either get CagriSema or a dummy medicine (also called "placebo") which has no effect on the body. Which treatment participants will get will be decided by chance. Participant's chance of getting CagriSema or placebo is the same. Participants will inject the study medicine once a week. The study medicine will be injected briefly with a thin needle, typically in the stomach, thighs or upper arms. The study will last for up to 4.5 years.
Interventions
DRUGCagrilintide
Participants will receive cagrilintide s.c. once-weekly after a dose escalation period of 16 weeks for 219 weeks.
DRUGSemaglutide
Participants will receive semaglutide s.c. once-weekly after a dose escalation period of 16 weeks for 219 weeks.
DRUGPlacebo
Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female * Age above or equal to 55 years at the time of signing informed consent * Body mass index (BMI) greater than or equal to (\>=) 25.0 kilograms per meter square (kg/m\^2) * Established CVD as evidenced by at least one of the following: 1. Prior myocardial infarction 2. Prior stroke (ischemic or haemorrhagic stroke) 3. Symptomatic peripheral arterial disease (PAD) defined as at least one of the following: 1. Intermittent claudication with an ankle-brachial index (ABI) less than (\<) 0.85 at rest 2. Intermittent claudication with a \>= 50% stenosis in a lower extremity peripheral artery documented by X-ray angiography, magnetic resonance (MR) angiography, computed tomography (CT) angiography or Doppler ultrasound 3. Prior revascularization procedure of a lower extremity peripheral artery 4. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis) For participants with T2D at screening the following inclusion criteria also apply: * Diagnosed with type 2 diabetes mellitus (T2D) \>= 180 days before screening * HbA1c 6.5%-10% (47-86 millimoles per mole \[mmol/mol\]) (both inclusive), as measured by central laboratory at screening * Treatment with either: 1. Lifestyle intervention alone 2. 1-3 marketed oral antidiabetic drugs (OADs) (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), dipeptidyl peptidase 4 (DPP4)-inhibitors, thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local label 3. Basal insulin alone or in combination with up to two marketed OADs, all according to local label
Exclusion criteria
* Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 60 days before screening * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening * Heart failure classified as being in New York Heart Association (NYHA) Class IV at screening * Treatment with any glucagon-like peptide-1 (GLP-1) receptor agonist (RA) or a medication with GLP-1 activity within 90 days before screening * End stage renal disease defined as estimated glomerular filtration rate (eGFR) \< 15 millileters per minutes per 1.73\^2 (mL/min/1.73 m\^2), as measured by the central laboratory at screening * Chronic or intermittent haemodialysis or peritoneal dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of 3-point major adverse cardiovascular event (MACE), a composite endpoint consisting of: cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change in body weight | From baseline (week 0) to 120 weeks | Measured in percentage (%). |
| Change in waist circumference | From baseline (week 0) to 120 weeks | Measured in centimeters (cm). |
| Change in waist-to-height ratio | From baseline (week 0) to 120 weeks | Measured in ratio. |
| Change in systolic blood pressure (SBP) | From baseline (week 0) to 120 weeks | Measured in millimeters of mercury (mmHg). |
| Change in diastolic blood pressure (DBP) | From baseline (week 0) to 120 weeks | Measured in mmHg. |
| Ratio to baseline in lipids: Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids | From baseline (week 0) to 120 weeks | Measured in ratio. |
| Change in glycated haemoglobin (HbA1c) | From baseline (week 0) to 120 weeks | Measured in percentage-points. |
| Number of treatment emergent serious adverse events (TESAEs) | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in count of events. |
| Number of event adjudication committee (EAC)-confirmed malignant neoplasms | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured as count of events. |
| Number of severe hypoglycaemic episodes (level 3) (only for participants with type 2 diabetes mellitus [T2D] at screening) | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured as count of events. |
| Change in eGFRcr (CKD-EPI) | From baseline (week 0) to 120 weeks | Measured in milliliter per min per 1.73 square meter (mL/min/1.73m\^2). |
| Time to first occurrence of myocardial infarction (fatal and non-fatal) | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in days. |
| Time to first occurrence of a composite endpoint: Onset of persistent ≥40% reduction in eGFRcr (CKD-EPI), eGFRcr (CKD-EPI) <15 mL/min/1.73 m^2, Initiation of chronic kidney replacement therapy, Kidney death and CV death | From baseline (week 0) to end of study (up to 242 weeks or more) | CKD-EPI is Chronic Kidney Disease Epidemiology Collaboration. Measured in days. |
| Time to first occurrence of composite endpoint consisting of: Onset of persistent macro albuminuria, ≥40% reduction in eGFRcr (CKD-EPI), eGFRcr (CKD-EPI) <15 mL/min/1.73 m^2, Initiation of chronic kidney replacement therapy and kidney death | From baseline (week 0) to end of study (up to 242 weeks or more) | CKD-EPI is Chronic Kidney Disease Epidemiology Collaboration. Measured in days. |
| Time to first occurrence of an expanded 5-point MACE composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation and unstable angina requiring hospitalisation | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in days. |
| Time to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction and non-fatal stroke | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in days. |
| Ratio to baseline in Urine albumin-to-creatinine ratio (UACR) | From baseline (week 0) to 120 weeks | Measured in ratio. |
| Time to first occurrence of stroke (fatal and non-fatal) | From baseline (week 0) to end of study (up to 242 weeks or more) | Measured in days. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Colombia, Denmark, France, Germany, India, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, Serbia, South Africa, Spain, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Transparency dept. 2834
Novo Nordisk A/S
Outcome results
None listed