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

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ClinicalTrials.gov Identifier: NCT05669755
Recruitment Status : Recruiting
First Posted : January 3, 2023
Last Update Posted : May 7, 2024
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Drug: Cagrilintide Drug: Semaglutide Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 1, 2023
Estimated Primary Completion Date : September 1, 2027
Estimated Study Completion Date : October 13, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Semaglutide

Arms and Interventions
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Arm Intervention/treatment
Experimental: CagriSema 2.4 mg/2.4 mg
Participants will receive 2.4 milligrams (mg) cagrilintide and 2.4 mg semaglutide subcutaneously (s.c.) once-weekly after a dose escalation period of 16 weeks during the maintenance period of 219 weeks.
 Drug: Cagrilintide
Participants will receive 2.4 mg cagrilintide s.c. once-weekly after a dose escalation period of 16 weeks for 219 weeks.

Drug: Semaglutide
Participants will receive 2.4 mg semaglutide s.c. once-weekly after a dose escalation period of 16 weeks for 219 weeks.
Placebo Comparator: Placebo
Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide s.c. once weekly for 235 weeks.
 Drug: Placebo
Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously.


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in days.


Secondary Outcome Measures :
  1. Time to occurrence of CV death [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in days.

  2. Time to first occurrence of a composite heart failure endpoint consisting of: CV death, heart failure, hospitalisation and urgent heart failure visit [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in days.

  3. 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 [ Time Frame: 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.

  4. Time to first occurrence of all-cause death [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in days.

  5. 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 [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in days.

  6. 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) ]
    Measured in days.

  7. 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) ]
    Measured in days.

  8. 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) ]
    Measured in days.

  9. Relative change in body weight [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in percentage (%).

  10. Change in waist circumference [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in centimeters (cm).

  11. Change in systolic blood pressure (SBP) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in millimeters of mercury (mmHg).

  12. Change in diastolic blood pressure (DBP) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in mmHg.

  13. 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 [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in percentage.

  14. Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in percentage-points.

  15. Change in Short Form 36 v2.0 acute (SF-36v2) [ Time Frame: 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).

  16. Number of treatment emergent serious adverse events (TESAEs) [ Time Frame: From baseline (week 0) to end of study (up to 242 weeks or more) ]
    Measured in count of events.

  17. 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) ]
    Measured as count of events.

  18. 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) ]
    Measured as count of events.

  19. Change from baseline in high-sensitivity C-reactive protein (hsCRP) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in milligram per liter (mg/L)

  20. Change from baseline in tumour necrosis factor alpha (TNF-α) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in picograms per milliliter (pg/mL)

  21. Change from baseline in Interleukin 6 (IL-6) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in pg/mL.

  22. Change from baseline in Interleukin 1 beta (IL-1β) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in pg/mL.

  23. Change in pain intensity rated by Numerical Rating Scale (NRS) [ Time Frame: 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'.

  24. Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 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.

  25. Change in neuropathy status by baseline neuropathy group (painful neuropathy, painless neuropathy or no neuropathy) [ Time Frame: From baseline (week 0) to 120 weeks ]
    Measured in percentage.


Eligibility Criteria
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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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% (48-86 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05669755


Contacts
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Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Transparency dept. 2834 Novo Nordisk A/S
More Information
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT05669755    
Other Study ID Numbers: NN9838-4942
U1111-1270-0943 ( Other Identifier: World Health Organization (WHO) )
2021-005855-35 ( EudraCT Number )
jRCT2031220672 ( Registry Identifier: jrct (Japan) )
First Posted: January 3, 2023    Key Record Dates
Last Update Posted: May 7, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cardiovascular Diseases
Semaglutide
Glucagon-Like Peptide-1 Receptor Agonists
Hypoglycemic Agents
Physiological Effects of Drugs