MK-0616 versus Comparators Study in Adults with Hypercholesterolemia

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

23 Aug 2024 → 28 Mar 2025

Decision date (initial)

2024-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504920-25-00

WHO UTN

U1111-1290-3888

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Efficacy, Pharmacogenetic, Therapy, Safety

To compare the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in low-density lipoprotein (LDL-C) at Day 56.

Secondary objectives 6

1. To compare the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in Apolipoprotein B (ApoB) at Day 56.
2. To compare the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in non-high-density lipoprotein (non-HDL-C) at Day 56.
3. To evaluate the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on percent change from baseline in Lipoprotein(a) [Lp(a)] at Day 56.
4. To evaluate the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on the proportion of participants who at Day 56 have an LDL-C <70 mg/dL and ≥50% reduction from baseline.
5. To evaluate the efficacy of MK-0616 against 3 comparators: ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on the proportion of participants who at Day 56 have an LDL-C<55 mg/dL and ≥50% reduction from baseline.
6. To evaluate the safety and tolerability of MK-0616

Conditions and MedDRA coding

Hypercholesterolemia

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 5

1. Has either a) history of a major atherosclerotic cardiovascular disease (ASCVD) event or b) if no history of a major ASCVD event, has intermediate to high risk for development of a first major ASCVD event.
2. Has fasted lipid values (evaluated by the central laboratory) at Visit 1 (Screening) as follows: a) history of a major ASCVD event with LDL-C ≥55 mg/dL (≥1.42 mmol/L) OR b) No history of a major ASCVD event with LDL-C ≥70 mg/dL (≥1.81 mmol/L)
3. Is treated with a low, moderate, or high intensity statin (±non-statin lipid lowering therapy [LLT])
4. Is on a stable dose of all background LLTs with no planned medication or dose changes during the study.
5. Is an individual of any sex/gender, from 18 years of age inclusive, at the time of providing the informed consent.

Exclusion criteria 6

1. Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous familial hypercholesterolemia (HeFH), or double HeFH
2. Has New York Heart Association class IV heart failure, or 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. Participants with a history of tendon disorder or tendon rupture
4. Participants with a history of gout
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean percent change from baseline in LDL-C at Day 56

Secondary endpoints 7

1. Mean percent change from baseline in ApoB at Day 56
2. Mean percent change from baseline in non-HDL-C at Day 56
3. Mean percent change from baseline in Lp(a) at Day 56
4. Percentage of participants who at Day 56 have an LDL-C <70 mg/dL and ≥50% reduction from baseline
5. Percentage of participants who at Day 56 have an LDL-C<55 mg/dL and ≥50% reduction from baseline
6. Number of participants with ≥1 adverse event (AE)
7. Number of participants discontinuing from study therapy due to AE

Investigational products

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

Test 1

Comparator 2

Placebo 3

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

Elina Mikhailova

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Elina Mikhailova

Third parties 3

Locations

2 EU/EEA countries · 9 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 35 files

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

Application history

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