A 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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Jun 2024 → ongoing

Decision date (initial)

2024-06-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502781-24-01

WHO UTN

U1111-1285-4245

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Pharmacogenomic, Efficacy, Therapy

1. To evaluate the efficacy of enlicitide decanoate (enlicitide) compared with placebo in increasing the time to the first event of coronary heart disease (CHD) death-based major adverse cardiovascular events (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 objectives 8

1. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to the first event of 3-point MACE
2. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to the first event of cardiovascular (CV) death-based MACE plus
3. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to the first event of either coronary heart disease death or myocardial infarction (MI)
4. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to cardiovascular death
5. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to all-cause death.
6. To evaluate the efficacy of enlicitide compared with placebo in increasing the time to the first event of each of the individual components of the primary endpoint: coronary heart disease death; MI; ischemic stroke; acute limb ischemia or major amputation; urgent arterial revascularization
7. To evaluate the effect of enlicitide compared with placebo on percent change from baseline in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, non-high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) at Week 52
8. To evaluate the safety and tolerability of enlicitide compared with placebo.

Conditions and MedDRA coding

ASCVD - Atherosclerotic Cardiovascular Disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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
2. 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)
3. Is treated with moderate- or high-intensity statin (± nonstatin LLT) at Visit 1
4. 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 7

1. CV Conditions: Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH
2. 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)
3. CV Conditions: Has recurrent ventricular tachycardia within 3 months prior to randomization
4. CV Conditions: Has a planned arterial revascularization procedure
5. 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
6. Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout.
7. Has a fasting triglyceride value ≥400 mg/dL (≥4.52 mmol/L) at Visit 1 (Screening)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CHD death-based MACE plus

Secondary endpoints 12

1. 3-point MACE
2. CV death-based MACE plus
3. Coronary heart disease death or MI
4. Cardiovascular death
5. All-cause death
6. Time to first event of MI, ischemic stroke, acute limb ischemia or major amputation, and urgent arterial revascularization
7. Percent change from baseline in LDL-C
8. Percent change from baseline in Apolipoprotein B
9. Percent change from baseline in Non-HDL-C
10. Percent change from baseline in Lipoprotein (a)
11. Number of participants with an adverse event (AE)
12. Number of participants discontinuing from study intervention due to AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Abena Osei-Wusu

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Abena Osei-Wusu

Third parties 8

Locations

9 EU/EEA countries · 184 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 118 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

27 submissions — initial application plus substantial / non-substantial modifications