ENLICITIDE CHLORIDE for Atherosclerotic cardiovascular disease (ASCVD)

Inclusion criteria

• {"criterion_text":"- Meets one of the following: a) 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 b) High risk for first major ASCVD event defined as at least 1 of the following: Age ≥50 years with evidence of coronary artery disease (CAD); Age ≥50 years with evidence of atherosclerotic cerebrovascular disease; Age ≥50 years with evidence of PAD; 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"}
• {"criterion_text":"- Has fasted lipid values (evaluated by the Central Laboratory) at Visit 1 (Screening) as follows: - 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) - 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)"}
• {"criterion_text":"- Is treated with moderate- or high-intensity statin (± nonstatin LLT) at Visit 1"}
• {"criterion_text":"- 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

• {"criterion_text":"- CV Conditions: Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH"}
• {"criterion_text":"- CV Conditions: 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)"}
• {"criterion_text":"- CV Conditions: Has recurrent ventricular tachycardia within 3 months prior to randomization"}
• {"criterion_text":"- CV Conditions: Has a planned arterial revascularization procedure"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout."}
• {"criterion_text":"- Has a fasting triglyceride value ≥400 mg/dL (≥4.52 mmol/L) at Visit 1 (Screening)"}

Primary endpoints

• {"endpoint_text":"- CHD death-based MACE plus","definition_or_measurement_approach":"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). Measured as time to first event (time-to-event analysis)."}

Secondary endpoints

• {"endpoint_text":"- 3-point MACE","definition_or_measurement_approach":"Time to first event of 3-point MACE (standard 3-point MACE components)."}
• {"endpoint_text":"- CV death-based MACE plus","definition_or_measurement_approach":"MACE plus defined using cardiovascular death as the anchor; time-to-first-event analysis."}
• {"endpoint_text":"- Coronary heart disease death or MI","definition_or_measurement_approach":"Time to first event of CHD death or myocardial infarction."}
• {"endpoint_text":"- Cardiovascular death","definition_or_measurement_approach":"Time to cardiovascular death."}
• {"endpoint_text":"- All-cause death","definition_or_measurement_approach":"Time to death from any cause."}
• {"endpoint_text":"- Time to first event of MI, ischemic stroke, acute limb ischemia or major amputation, and urgent arterial revascularization","definition_or_measurement_approach":"Time-to-event for each listed component."}
• {"endpoint_text":"- Percent change from baseline in LDL-C","definition_or_measurement_approach":"Percent change from baseline in LDL-C; secondary objectives specify measurement at Week 52."}
• {"endpoint_text":"- Percent change from baseline in Apolipoprotein B","definition_or_measurement_approach":"Percent change from baseline in apolipoprotein B (measurement timing per protocol, e.g., Week 52 specified for lipid endpoints)."}
• {"endpoint_text":"- Percent change from baseline in Non-HDL-C","definition_or_measurement_approach":"Percent change from baseline in non-HDL cholesterol."}
• {"endpoint_text":"- Percent change from baseline in Lipoprotein (a)","definition_or_measurement_approach":"Percent change from baseline in lipoprotein(a)."}
• {"endpoint_text":"- Number of participants with an adverse event (AE)","definition_or_measurement_approach":"Count of participants experiencing at least one AE (safety monitoring)."}
• {"endpoint_text":"- Number of participants discontinuing from study intervention due to AE","definition_or_measurement_approach":"Count of participants who discontinue study intervention because of an AE."}

Methods

• Social media advertising (country-specific materials present, e.g., Denmark, France, Germany) targeting potential participants/patients
• Website and online banner advertisements (program/0616-015 websites and online adverts)
• Posters and printed materials displayed in clinics and hospitals
• Patient flyers, brochures, welcome brochures and study cards given to potential participants
• Patient letters sent to potential participants
• Print advertisements (newspapers/print media) and patient print ads
• Patient appointment/visit cards and visit calendars to support scheduling
• Prescreening and digital recruitment services provided by third parties (e.g., Reify Health, StudyKik) including prescreening activities
• EUB Call Center and medical escalation service (third-party support for recruitment enquiries)
• Country-specific recruitment packs and materials (K1/K2 documents and ICFs available in multiple languages for each country)

Norway

Earliest CTIS Part Ii Submission Date

24-05-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

627

Number Of Participants

150

Poland

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

623

Number Of Participants

850

Netherlands

Earliest CTIS Part Ii Submission Date

24-05-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

628

Number Of Participants

600

Italy

Earliest CTIS Part Ii Submission Date

06-03-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

706

Number Of Participants

130

Denmark

Earliest CTIS Part Ii Submission Date

07-05-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

643

Number Of Participants

310

France

Earliest CTIS Part Ii Submission Date

18-05-2024

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

646

Number Of Participants

45

Hungary

Earliest CTIS Part Ii Submission Date

24-05-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

700

Number Of Participants

600

Spain

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

641

Number Of Participants

300

Germany

Earliest CTIS Part Ii Submission Date

24-05-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

700

Number Of Participants

250

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Perceptive Eclinical Limited

Responsibilities

EUB Call Center and Medical Escalation Service

Name

Parexel International Corp.

Responsibilities

Medical information (Physician Consulting)

Name

Reify Health

Responsibilities

Prescreening services and recruitment activities

Name

Signant Health Global LLC

Responsibilities

code:3

Name

Perceptive Eclinical Limited

Responsibilities

EUB Call Center and Medical Escalation Service

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Stanford Quantitative Sciences Unit","duties_or_roles":"Medical expertise: External Data Monitoring Committee","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"EUB Call Center and Medical Escalation Service","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group","duties_or_roles":"Endpoint Adjudication","organisation_type":"Industry"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Reify Health","duties_or_roles":"Prescreening services and recruitment activities","organisation_type":"Industry"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Medical information (Physician Consulting)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"StudyKik","duties_or_roles":"Patient recruitment and prescreening services and custom patient retention applications","organisation_type":"Industry"}