REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels
- Conditions
- Cardiovascular Disease
- Interventions
- Registration Number
- NCT05669755
- Lead Sponsor
- Novo Nordisk A/S
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 7000
-
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)
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Established CVD as evidenced by at least one of the following:
-
Prior myocardial infarction
-
Prior stroke (ischemic or haemorrhagic stroke)
-
Symptomatic peripheral arterial disease (PAD) defined as at least one of the following:
- Intermittent claudication with an ankle-brachial index (ABI) less than (<) 0.85 at rest
- 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
- Prior revascularization procedure of a lower extremity peripheral artery
- Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis)
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For participants with T2D at screening the following inclusion criteria also apply:
-
Diagnosed with type 2 diabetes mellitus (T2D) >= 180 days before screening
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HbA1c 6.5%-10% (48-86 millimoles per mole [mmol/mol]) (both inclusive), as measured by central laboratory at screening
-
Treatment with either:
- Lifestyle intervention alone
- 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
- Basal insulin alone or in combination with up to two marketed OADs, all according to local label
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CagriSema Cagrilintide 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. CagriSema Semaglutide 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 Placebo Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide s.c. once weekly for 235 weeks.
- Primary Outcome Measures
Name Time Method Time to first occurrence of 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 Outcome Measures
Name Time Method Change in diastolic blood pressure (DBP) From baseline (week 0) to 120 weeks Measured in mmHg.
Relative change 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 percentage.
Change in glycated haemoglobin (HbA1c) From baseline (week 0) to 120 weeks Measured in percentage-points.
Change from baseline in Interleukin 1 beta (IL-1β) From baseline (week 0) to 120 weeks Measured in pg/mL.
Change in Pittsburgh Sleep Quality Index (PSQI) From baseline (week 0) to 120 weeks The Pittsburgh Sleep Quality Index is a 19-item, self-rated questionnaire, assessed various aspects of sleep, sleep quality, and sleep disturbances. The PSQI is composed of 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score. An overall score ranges from 0 to 21, where lower scores denote a healthier sleep quality.
Time to occurrence of CV death From baseline (week 0) to end of study (up to 242 weeks or more) Measured in days.
Time to first occurrence of a composite heart failure endpoint consisting of: CV death, heart failure, hospitalisation and urgent heart failure visit From baseline (week 0) to end of study (up to 242 weeks or more) Measured in days.
Time to first occurrence of an expanded 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: Onset of persistent ≥40% reduction in eGFRcr (CKD-EPI), Onset of persistent eGFRcr (CKD-EPI) <15 mL/min/1.73 m2, Initiation of chronic kidney replacement therapy, Kidney death and CV death From baseline (week -3) 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 all-cause death 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.
Change in waist circumference From baseline (week 0) to 120 weeks Measured in centimeters (cm).
Change in systolic blood pressure (SBP) From baseline (week 0) to 120 weeks Measured in millimeters of mercury (mmHg).
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 Short Form 36 v2.0 acute (SF-36v2) From baseline (week 0) to 120 weeks SF-36v2.0 is a 36-item commonly used generic clinical outcome assessment (COA) instrument measuring health-related quality of life and general health status across disease areas. The SF-36v2.0 for adults with a 1 week recall period (i.e. acute version) measures the individual overall health-related quality of life in 8 health domains (physical functioning, role-physical, bodily pain, general health, social functioning, role emotional, vitality and mental health). Furthermore, it includes two aggregated scores: a physical component summary score and a mental component summary score. Range of score for domains and component summary scores : 1-100 (Higher scores indicated a better health state).
Change from baseline in tumour necrosis factor alpha (TNF-α) From baseline (week 0) to 120 weeks Measured in picograms per milliliter (pg/mL)
Change from baseline in Interleukin 6 (IL-6) From baseline (week 0) to 120 weeks Measured in pg/mL.
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 stroke (fatal and non-fatal) From baseline (week 0) to end of study (up to 242 weeks or more) Measured in days.
Relative change in body weight From baseline (week 0) to 120 weeks Measured in percentage (%).
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.
Change from baseline in high-sensitivity C-reactive protein (hsCRP) From baseline (week 0) to 120 weeks Measured in milligram per liter (mg/L)
Change in pain intensity rated by Numerical Rating Scale (NRS) From baseline (week 0) to 120 weeks The NRS rates average pain intensity in the last 24 hours on a scale from 0 to 10, with 0 meaning 'No pain' and '10' meaning 'Pain as bad as you can imagine'.
Change in neuropathy status by baseline neuropathy group (painful neuropathy, painless neuropathy or no neuropathy) From baseline (week 0) to 120 weeks Measured in percentage.
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.
Trial Locations
- Locations (556)
Univ of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Chambliss Clinical Trials LLC
🇺🇸Montgomery, Alabama, United States
Honor Health
🇺🇸Scottsdale, Arizona, United States
National Heart Institute Cal
🇺🇸Beverly Hills, California, United States
Valley Clinical Trials
🇺🇸Covina, California, United States
Scripps Wht Diab Inst La Jolla
🇺🇸La Jolla, California, United States
First Valley Medical Group
🇺🇸Lancaster, California, United States
Clinical Trials Research_Sacramento
🇺🇸Lincoln, California, United States
Torrance Clin Res Inst, Inc.
🇺🇸Lomita, California, United States
Pacific Clinical Studies
🇺🇸Los Alamitos, California, United States
Scroll for more (546 remaining)Univ of Alabama Birmingham🇺🇸Birmingham, Alabama, United States