Arteriosclerosis, Hypercholesterolaemia
Conditions
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.
Interventions
Enlicitide Decanoate 20 mg tablet taken by mouth.
DRUGPlacebo
Placebo tablet matched to enlicitide decanoate taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The blinded period is double-blinded. The extension period is open-label.
Intervention model description
There are two parts of the study. The blinded period is randomized parallel treatment groups. Participants who complete the blinded period are then eligible to enroll in an open label extension (OLE) (single group).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blinded Period: 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
| Measure | Time frame | Description |
|---|---|---|
| Blinded Period: 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). |
| Blinded Period: 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). |
| Blinded Period: 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. |
| Blinded Period: Time to CV Death | From date of randomization until the date of CV death, assessed up to approximately 6 years | Time to cardiovascular death. |
| Blinded Period: 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. |
| Blinded Period: Time to CHD Death | From date of randomization until the date of CHD death, assessed up to approximately 6 years | Time to CHD death. |
| Blinded Period: 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. |
| Blinded Period: 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. |
| Blinded Period: 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. |
| Blinded Period: 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). |
| Blinded Period: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | Baseline and Week 52 | The percent change from baseline in LDL-C. |
| Blinded Period: Percent Change from Baseline in Apolipoprotein B | Baseline and Week 52 | The percent change from baseline in apolipoprotein B. |
| Blinded Period: 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. |
| Blinded Period: Percent Change from Baseline in Lipoprotein (a) | Baseline and Week 52 | The percent change from baseline in lipoprotein (a). |
| Blinded Period: Number of Participants with an Adverse Event (AE) | 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. |
| Blinded Period: Number of Participants Discontinuing from Study Therapy Due to AE | 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. |
| Open-Label Extension (OLE): Time to First Occurrence of CHD Death-Based MACE Plus | 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). |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Puerto Rico, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed