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

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ClinicalTrials.gov Identifier: NCT06008756
Recruitment Status : Recruiting
First Posted : August 24, 2023
Last Update Posted : April 8, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:
This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of MK-0616, 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 MK-0616 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.

Condition or disease Intervention/treatment Phase
Arteriosclerosis Hypercholesterolaemia Drug: MK-0616 Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 9, 2023
Estimated Primary Completion Date : November 29, 2029
Estimated Study Completion Date : November 29, 2029
Arms and Interventions
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Arm Intervention/treatment
Experimental: MK-0616
Participants receive MK-0616 20 mg once daily.
 Drug: MK-0616
MK-0616 20 mg tablet taken by mouth.
Placebo Comparator: Placebo
Participants receive placebo once daily.
 Drug: Placebo
Placebo tablet matched to MK-0616 taken by mouth.


Outcome Measures
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Primary Outcome Measures :
  1. Time to First Occurrence of Coronary Heart Disease (CHD) Death-Based Major Adverse Cardiovascular Events (MACE)-Plus [ Time Frame: 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 :
  1. Time to First Occurrence of 3-point MACE [ Time Frame: 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. Time to First Occurrence of Cardiovascular (CV) Death-Based MACE Plus [ Time Frame: 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. Time to 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 ]
    Time to the first occurrence of CHD death or MI.

  4. Time to CV Death [ Time Frame: From date of randomization until the date of CV death, assessed up to approximately 6 years ]
    Time to cardiovascular death.

  5. Time to All-Cause Death [ Time Frame: From date of randomization until the date of death, assessed up to approximately 6 years ]
    Time to all-cause death.

  6. Time to CHD Death [ Time Frame: From date of randomization until the date of CHD death, assessed up to approximately 6 years ]
    Time to CHD death.

  7. Time to First Event of MI [ Time Frame: From date of randomization until the date of MI, assessed up to approximately 6 years ]
    Time to the first occurrence of MI.

  8. Time to First Event of Ischemic Stroke [ Time Frame: 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. Time to First Event 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 ]
    Time to the first occurrence of acute limb ischemia or major amputation.

  10. Time to First Event of Urgent Arterial Revascularization [ Time Frame: 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. Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline and Week 52 ]
    The percent change from baseline in LDL-C.

  12. Percent Change from Baseline in Apolipoprotein B [ Time Frame: Baseline and Week 52 ]
    The percent change from baseline in apolipoprotein B.

  13. Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) cholesterol [ Time Frame: Baseline and Week 52 ]
    The percent change from baseline in Non-HDL-C.

  14. Percent Change from Baseline in Lipoprotein (a) [ Time Frame: Baseline and Week 52 ]
    The percent change from baseline in lipoprotein (a).

  15. Number of Participants with an Adverse Event (AE) [ Time Frame: 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.

  16. Number of Participants Discontinuing from Study Therapy Due to AE [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • Has history of severe renal insufficiency defined as estimated glomerular filtration rate <30 mL/min/1.73 m2 at Visit 1 (Screening) or has end-stage renal disease on 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): NCT06008756


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT06008756    
Other Study ID Numbers: 0616-015
jRCT2071230064 ( Registry Identifier: Japan Registry of Clinical Trials (jRCT) )
2022-502781-24 ( Other Identifier: EU CT )
First Posted: August 24, 2023    Key Record Dates
Last Update Posted: April 8, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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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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Arteriosclerosis
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
 Metabolic Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases