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

Short name REDEFINE 3

NCTNCT05669755Other idNN9838-4942Other idU1111-1270-0943Other id2021-005855-35Other idjRCT2031220672

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Active, not recruiting
Phase: Phase 3
Enrollment: 7,101 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 25 countries
United States, 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
Start: 1 Mar 2023
Primary completion: 1 Sept 2027 (estimated)
Completion: 14 Oct 2027 (estimated)
First posted: 3 Jan 2023
Last update posted: 31 Aug 2026
Conditions: Cardiovascular Disease

Timeline

1 trial · 1 ongoing

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

202320242025202620272028

Ph 3
REDEFINE 3
NCT05669755
1 Mar 2023 to est. 14 Oct 2027

Registry summary

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

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

CagrilintideDrug
SemaglutideDrug
PlaceboDrug

Arms2

Experimental
CagriSema
Participants will receive cagrilintide and semaglutide subcutaneously (s.c.) once-weekly after a dose escalation period of 16 weeks during the maintenance period of 219 weeks.
Placebo comparator
Placebo
Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide s.c. once weekly for 235 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

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)
Registry description
Measured in days.

Secondary outcomes(18)

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)
Registry description
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
Time frame · From baseline (week 0) to end of study (up to 242 weeks or more)
Registry description
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
Time frame · From baseline (week 0) to end of study (up to 242 weeks or more)
Registry description
Measured in days.
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)
Registry description
Measured in days.
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)
Registry description
Measured in days.
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)
Registry description
Measured in days.
Change in eGFRcr (CKD-EPI)
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in milliliter per min per 1.73 square meter (mL/min/1.73m\^2).
Ratio to baseline in Urine albumin-to-creatinine ratio (UACR)
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in ratio.
Relative change in body weight
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in percentage (%).
Change in waist circumference
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in centimeters (cm).
Change in waist-to-height ratio
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in ratio.
Change in systolic blood pressure (SBP)
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in millimeters of mercury (mmHg).
Change in diastolic blood pressure (DBP)
Time frame · From baseline (week 0) to 120 weeks
Registry description
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
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in ratio.
Change in glycated haemoglobin (HbA1c)
Time frame · From baseline (week 0) to 120 weeks
Registry description
Measured in percentage-points.
Number of treatment emergent serious adverse events (TESAEs)
Time frame · From baseline (week 0) to end of study (up to 242 weeks or more)
Registry description
Measured in count of events.
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)
Registry description
Measured as count of events.
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)
Registry description
Measured as count of events.

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.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedCavender MA, Jastreboff AM, Cheng AYY, Davies MJ, Donaldson L, Gerlach LO, Gylvin SH, Jacobsen JB, Marx N, Osorto Contreras CK, Le Roux CW, Lincoff AM. Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3). Am Heart J. 2026 Oct 6:107626. doi: 10.1016/j.ahj.2026.107626. Online ahead of print. PMID 42838477

Eligibility

Who could join, as posted.

Sex: All
Age: from 55 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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