REDEFINE 3

Active not recruitingPhase 3

REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels

The Cardiovascular Safety and Efficacy of Cagrilintide 2.4 mg s.c. in Combination With Semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) Once-weekly in Participants With Established Cardiovascular Disease

Lead sponsor

Novo Nordisk A/S

Assets

CagriSema / cagrilintide / Semaglutide

Listed sites

631

Recruiting sites

—

Enrollment

7,101

actual

Study population

Cardiovascular disease, Obesity / overweight

Key I/E criterion

•HbA1c 6.5-10%

Primary endpoint

•3-point MACE (Cardiovascular death, Non-fatal MI, Non-fatal stroke)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05669755

Org study IDNN9838-4942

Secondary ID2021-005855-35

Secondary IDjRCT2031220672jrct (Japan)

Secondary IDU1111-1270-0943World Health Organization (WHO)

Timeline

Milestones

Study first posted2023-01-03actual

Study start2023-03-01actual

Last update posted2026-05-19actual

Primary completion2027-09-01estimated

Study completion2027-10-13estimated

Assets

Investigational agents

CagriSema / cagrilintide Semaglutide

Study populations

Who this study enrolls

Cardiovascular diseaseObesity / overweight

Eligibility

Who can enroll

Minimum age55 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (19)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Cardiovascular outcomes

Renal / kidney

Weight & body composition

Cardiometabolic biomarkers

Safety / tolerability / PK

Glycemic / diabetes

Cardiovascular outcomes

5 endpoints

Primary/protocol endpoint

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

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

5-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke, Coronary revascularization, Unstable angina hospitalization

Secondary/protocol endpoint

Time to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction and non-fatal stroke

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Non-fatal MI, Non-fatal stroke

Secondary/protocol endpoint

Time to first occurrence of myocardial infarction (fatal and non-fatal)

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Myocardial infarction (any)

time to event, event

SNOMED 22298006

Secondary/protocol endpoint

Time to first occurrence of stroke (fatal and non-fatal)

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Stroke (any)

time to event, event

SNOMED 230690007

Weight & body composition

3 endpoints

Secondary/protocol endpoint

Relative change in body weight

Time frame:From baseline (week 0) to 120 weeks

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:From baseline (week 0) to 120 weeks

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in waist-to-height ratio

Time frame:From baseline (week 0) to 120 weeks

change from baseline, improvement

Glycemic / diabetes

1 endpoint

Secondary/protocol endpoint

Change in glycated haemoglobin (HbA1c)

Time frame:From baseline (week 0) to 120 weeks

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Renal / kidney

4 endpoints

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Custom renal composite

time to event, event

componentseGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death, Cardiovascular death

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Custom renal composite

time to event, event

componentsuACR, change, eGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death

Secondary/protocol endpoint

Change in eGFRcr (CKD-EPI)

Time frame:From baseline (week 0) to 120 weeks

eGFR, change

change from baseline, improvement

LOINC 98979-8

Secondary/protocol endpoint

Ratio to baseline in Urine albumin-to-creatinine ratio (UACR)

Time frame:From baseline (week 0) to 120 weeks

uACR, change

ratio, improvement

LOINC 9318-7

Cardiometabolic biomarkers

3 endpoints

Secondary/protocol endpoint

Change in systolic blood pressure (SBP)

Time frame:From baseline (week 0) to 120 weeks

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in diastolic blood pressure (DBP)

Time frame:From baseline (week 0) to 120 weeks

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to 120 weeks

ratio, improvement

Safety / tolerability / PK

3 endpoints

Secondary/protocol endpoint

Number of treatment emergent serious adverse events (TESAEs)

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Number of event adjudication committee (EAC)-confirmed malignant neoplasms

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

event count, event

Secondary/protocol endpoint

Number of severe hypoglycaemic episodes (level 3) (only for participants with type 2 diabetes mellitus [T2D] at screening)

Time frame:From baseline (week 0) to end of study (up to 242 weeks or more)

Severe hypoglycemia

event count, event

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.