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

Phase 3Active Not RecruitingNCT06008756

Merck Sharp & Dohme LLC14,550 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

14,550

Conditions

Arteriosclerosis Hypercholesterolaemia

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (669)

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

Outcomes

Primary Outcomes

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

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).

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

Secondary Outcomes

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

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

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

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

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

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

Time to the first occurrence of CHD death or MI.

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

Blinded Period: Time to CV Death

Time to cardiovascular death.

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

Blinded Period: Time to All-Cause Death

Time to all-cause death.

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

Blinded Period: Time to CHD Death

Time to CHD death.

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

Blinded Period: Time to First Event of MI

Time to the first occurrence of MI.

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

Blinded Period: Time to First Event of Ischemic Stroke

Time to the first occurrence of ischemic stroke.

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

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

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

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

Blinded Period: Time to First Event of Urgent Arterial Revascularization

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

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

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

The percent change from baseline in LDL-C.

Time frame: Baseline and Week 52

Blinded Period: Percent Change from Baseline in Apolipoprotein B

The percent change from baseline in apolipoprotein B.

Time frame: Baseline and Week 52

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

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

Time frame: Baseline and Week 52

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

The percent change from baseline in lipoprotein (a).

Time frame: Baseline and Week 52

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

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.

Time frame: Up to approximately 6 years

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

Time frame: Up to approximately 6 years

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

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).

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