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

Phase 3

Active, not recruiting

• Conditions: Arteriosclerosis; Hypercholesterolaemia
• Interventions: Drug: Enlicitide Decanoate; Drug: Placebo

• Registration Number: NCT06008756
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-17
• Study First Submitted QC: 2023-08-17
• Study First Posted: 2023-08-24
• Study Start: 2023-10-09
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-10
• Last Update Posted: 2025-07-14
• Primary Completion: 2029-11-29
• Study Completion: 2029-11-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 14550

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enlicitide Decanoate	Enlicitide Decanoate	Participants receive enlicitide decanoate 20 mg once daily.
Placebo	Placebo	Participants receive placebo once daily.

Primary Outcome Measures

Name	Time	Method
Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus	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).

Secondary Outcome Measures

Name	Time	Method
Time to First Event of MI	From date of randomization until the date of MI, assessed up to approximately 6 years	Time to the first occurrence of MI.
Time to First Occurrence of 3-point MACE	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).
Time to First Occurrence of Cardiovascular (CV) Death-Based MACE Plus	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).
Time to CV Death	From date of randomization until the date of CV death, assessed up to approximately 6 years	Time to cardiovascular death.
Number of Participants Discontinuing from Study Therapy Due to AE	Up to ~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.
Time to First Occurrence of CHD Death or MI	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.
Time to All-Cause Death	From date of randomization until the date of death, assessed up to approximately 6 years	Time to all-cause death.
Time to First Event of Urgent Arterial Revascularization	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).
Percent Change from Baseline in Apolipoprotein B	Baseline and Week 52	The percent change from baseline in apolipoprotein B.
Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) cholesterol	Baseline and Week 52	The percent change from baseline in Non-HDL-C.
Percent Change from Baseline in Lipoprotein (a)	Baseline and Week 52	The percent change from baseline in lipoprotein (a).
Time to CHD Death	From date of randomization until the date of CHD death, assessed up to approximately 6 years	Time to CHD death.
Time to First Event of Ischemic Stroke	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.
Time to First Event of Acute Limb Ischemia or Major Amputation	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.
Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)	Baseline and Week 52	The percent change from baseline in LDL-C.
Number of Participants with an Adverse Event (AE)	Up to ~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.

Trial Locations

Locations (668)

Advanced Cardiovascular - Alexander City ( Site 0156); 🇺🇸 Alexander City, Alabama, United States

Central Research Associates ( Site 0118); 🇺🇸 Birmingham, Alabama, United States

St. Vincent's Birmingham Hospital ( Site 0181); 🇺🇸 Birmingham, Alabama, United States

Central Alabama Research ( Site 0109); 🇺🇸 Birmingham, Alabama, United States

Alliance for Multispecialty Research, LLC ( Site 0076); 🇺🇸 Daphne, Alabama, United States

G&L Research ( Site 0042); 🇺🇸 Foley, Alabama, United States

NextStage Clinical Research - Phoenix - (01) ( Site 0191); 🇺🇸 Glendale, Arizona, United States

Synexus Clinical Research US, Inc.-Synexus Clinical Research US, Inc - Central Phoenix ( Site 0066); 🇺🇸 Phoenix, Arizona, United States

Medical Investigations Inc. ( Site 0188); 🇺🇸 Little Rock, Arkansas, United States

National Heart Institute-Research ( Site 0077); 🇺🇸 Beverly Hills, California, United States

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