Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) CORALreef Outcomes

NCT06008756
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
14,550
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2023-10-09
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Number of sites
669
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Summary
This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of enlicitide decanoate, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in participants with high cardiovascular risk. The primary objective is to evaluate the efficacy of enlicitide decanoate compared with placebo in increasing the time to the first occurrence of major adverse cardiovascular events (MACE) including coronary heart disease (CHD) death, ischemic stroke, myocardial infarction (MI), acute limb ischemia or major amputation, or urgent arterial revascularization.
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Short title
Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) CORALreef Outcomes
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Official title
Phase 3 Randomized, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of MK-0616 in Reducing Major Adverse Cardiovascular Events in Participants at High Cardiovascular Risk
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2031-11-29
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First posted
2023-08-24
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Registry last updated
2026-04-23
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Primary completion date
2029-11-29
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Start date
2023-10-09
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Participants
14,550
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Participant count basis
Estimated
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Planned participants
14,550
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Protocol amendments
4
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Number of sites
669
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06008756
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ClinicalTrials.gov ID
NCT06008756
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Triple masking
Masking description
The blinded period is double-blinded. The extension period is open-label.
Masked roles
Participants, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Blinded Period: Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus

    Timeframe: From date of randomization until the date of first occurrence of CHD death-based MACE-plus, assessed up to approximately 6 years

    Time to the first occurrence of CHD death-based MACE-plus, which is defined as any of the following: coronary heart disease death, myocardial infarction (MI), ischemic stroke (fatal and nonfatal), acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).

  1. Blinded Period: Time to First Occurrence of 3-point MACE

    Timeframe: From date of randomization until the date of first occurrence of 3-point MACE, assessed up to approximately 6 years

    Time to the first occurrence of 3-point MACE (defined as cardiovascular death, MI, or ischemic stroke).

  2. Blinded Period: Time to First Occurrence of Cardiovascular (CV) Death-Based MACE Plus

    Timeframe: From date of randomization until the date of first occurrence of CV death-based MACE plus, assessed up to approximately 6 years

    Time to the first occurrence of CV death-based MACE plus, defined as any of the following: cardiovascular death, MI, ischemic stroke, acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).

  3. Blinded Period: Time to First Occurrence of CHD Death or MI

    Timeframe: From date of randomization until the date of first occurrence of CHD death or MI, assessed up to approximately 6 years

    Time to the first occurrence of CHD death or MI.

  4. Blinded Period: Time to CV Death

    Timeframe: From date of randomization until the date of CV death, assessed up to approximately 6 years

    Time to cardiovascular death.

  5. Blinded Period: Time to All-Cause Death

    Timeframe: From date of randomization until the date of death, assessed up to approximately 6 years

    Time to all-cause death.

  6. Blinded Period: Time to CHD Death

    Timeframe: From date of randomization until the date of CHD death, assessed up to approximately 6 years

    Time to CHD death.

  7. Blinded Period: Time to First Event of MI

    Timeframe: From date of randomization until the date of MI, assessed up to approximately 6 years

    Time to the first occurrence of MI.

  8. Blinded Period: Time to First Event of Ischemic Stroke

    Timeframe: From date of randomization until the date of first occurrence of ischemic stroke, assessed up to approximately 6 years

    Time to the first occurrence of ischemic stroke.

  9. Blinded Period: Time to First Event of Acute Limb Ischemia or Major Amputation

    Timeframe: From date of randomization until the date of first occurrence of acute limb ischemia or major amputation, assessed up to approximately 6 years

    Time to the first occurrence of acute limb ischemia or major amputation.

  10. Blinded Period: Time to First Event of Urgent Arterial Revascularization

    Timeframe: From date of randomization until the date of urgent arterial revascularization, assessed up to approximately 6 years

    Time to the first occurrence of urgent arterial revascularization (coronary, cerebrovascular, or peripheral).

  11. Blinded Period: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)

    Timeframe: Baseline and Week 52

    The percent change from baseline in LDL-C.

  12. Blinded Period: Percent Change from Baseline in Apolipoprotein B

    Timeframe: Baseline and Week 52

    The percent change from baseline in apolipoprotein B.

  13. Blinded Period: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) cholesterol

    Timeframe: Baseline and Week 52

    The percent change from baseline in Non-HDL-C.

  14. Blinded Period: Percent Change from Baseline in Lipoprotein (a)

    Timeframe: Baseline and Week 52

    The percent change from baseline in lipoprotein (a).

  15. Blinded Period: Number of Participants with an Adverse Event (AE)

    Timeframe: Up to approximately 6 years

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AE(s) in each arm will be reported.

  16. Blinded Period: Number of Participants Discontinuing from Study Therapy Due to AE

    Timeframe: Up to approximately 6 years

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants discontinuing due to AE(s) in each arm will be reported.

  17. Open-Label Extension (OLE): Time to First Occurrence of CHD Death-Based MACE Plus

    Timeframe: From date of randomization until the date of first occurrence of CHD death-based MACE plus, assessed up to approximately 8 years

    Time to the first occurrence of CHD death-based MACE-plus, which is defined as any of the following: coronary heart disease death, MI, ischemic stroke (fatal and nonfatal), acute limb ischemia or major amputation, or urgent arterial revascularization (coronary, cerebrovascular, or peripheral).

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Meets one of the following:

    1. Age ≥18 years with a history of a major atherosclerotic cardiovascular disease (ASCVD) event defined as at least 1 of the following: ≥30 days post MI (presumed Type 1 due to plaque rupture or erosion); ≥30 days post ischemic stroke (presumed due to atherosclerosis); or ≥30 days post successful peripheral (carotid or lower extremity) arterial revascularization (surgical or endovascular) or major (ankle or above) amputation due to atherosclerosis; or
    2. High risk for first major ASCVD event defined as at least 1 of the following: Age ≥50 years with evidence of coronary artery disease; Age ≥50 years with evidence of atherosclerotic cerebrovascular disease; Age ≥50 years with evidence of peripheral arterial disease; or Age ≥60 years with diabetes mellitus and at least one of the following: microvascular disease or urine albumin-creatinine ratio ≥30 mg/mmol within 6 months before Visit 1, daily insulin use, or diabetes for ≥10 years

  • Has fasted lipid values (evaluated by the Central Laboratory) at Visit 1 (Screening) as follows:

    1. History of major ASCVD Event: LDL-C ≥70 mg/dL (1.81 mmol/L) OR non-HDL-C ≥100 mg/dL (2.59 mmol/L)
    2. High risk for first major ASCVD Event: LDL-C ≥90 mg/dL (2.33 mmol/L) OR non-HDL-C ≥120 mg/dL (3.11 mmol/L)

  • Is treated with moderate- or high-intensity statin (± nonstatin lipid-lowering therapy [LLT]) at Visit 1

  • Is on a stable dose of all background LLTs (including statin and nonstatin agents) for at least 30 days before Visit 1 (Screening) with no medication or dose changes planned during the participation in the study

  • Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH
  • Has New York Heart Association Class IV heart failure, last known Left Ventricular Ejection Fraction ≤25% by any imaging method, or had a Heart Failure hospitalization within 3 months before Visit 1 (Screening)
  • Has recurrent ventricular tachycardia within 3 months prior to randomization
  • Has a planned arterial revascularization procedure
  • Is undergoing or previously underwent an LDL-C apheresis program within 3 months before Visit 1 (Screening) or plans to initiate an LDL-C apheresis program
  • Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout.
  • Has a fasting triglyceride value ≥400 mg/dL (≥4.52 mmol/L) at Visit 1 (Screening)
Sources for eligibility
clinicaltrials.gov

  • Advanced Cardiovascular - Alexander City ( Site 0156)Alexander City, United States
  • Central Research Associates ( Site 0118)Birmingham, United States
  • St. Vincent's Birmingham Hospital ( Site 0181)Birmingham, United States
  • Central Alabama Research ( Site 0109)Birmingham, United States
  • Alliance for Multispecialty Research, LLC ( Site 0076)Daphne, United States
  • G&L Research ( Site 0042)Foley, United States
  • NextStage Clinical Research - Phoenix - (01) ( Site 0191)Glendale, United States
  • Synexus Clinical Research US, Inc.-Synexus Clinical Research US, Inc - Central Phoenix ( Site 0066)Phoenix, United States
  • Medical Investigations Inc. ( Site 0188)Little Rock, United States
  • National Heart Institute-Research ( Site 0077)Beverly Hills, United States
  • UCSD - Altman Clinical and Translational Research Institute (ACTRI) ( Site 0130)La Jolla, United States
  • Chemidox Clinical Trials ( Site 0145)Lancaster, United States
  • Velocity Clinical Research, Westlake ( Site 0039)Los Angeles, United States
  • Carbon Health - Pasadena ( Site 0149)Pasadena, United States
  • Carbon Health - San Mateo - Hillsdale Mall ( Site 0151)San Mateo, United States
  • America Clinical Trials-Research Dept ( Site 0104)Tarzana, United States
  • Premiere Medical Center ( Site 0093)Toluca Lake, United States
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center ( Site 0058)Torrance, United States
  • University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular ( Site 0146)Aurora, United States
  • South Denver Cardiology Associates ( Site 0167)Littleton, United States
  • Cardiology Associates of Fairfield County, P.C. ( Site 0159)Stamford, United States
  • Chase Medical Research, LLC ( Site 0046)Waterbury, United States
  • Emerson Clinical Research Institute ( Site 0143)Washington D.C., United States
  • Excel Medical Clinical Trials ( Site 0052)Boca Raton, United States
  • Advanced Pharma Research ( Site 0040)Cutler Bay, United States

And 644 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • U1111-1285-4245
  • 2022-502781-24-00
  • jRCT2071230064
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)