A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)

NCT05952869 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 0616-017MK-0616-0172022-502782-14-00U1111-1285-4257
• Study Type: interventional
• Target: 303
• Locations: 17 countries
• Sites: 59

Brief Summary

The goal of this study is to evaluate the efficacy, safety, and tolerability of enlicitide decanoate in adult participants with heterozygous familial hypercholesterolemia. The primary hypothesis is that enlicitide decanoate is superior to placebo on mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24.

Conditions

Hypercholesterolemia; Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (3)

• Mean Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24

  Blood samples were collected at baseline and at Week 24 to determine mean percent change in LDL-C. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline LDL-C as a covariate.

  Baseline and Week 24

• Number of Participants With Adverse Events (AEs)

  An AE was defined as 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.

  Up to 64 weeks (8 weeks postdose)

• Number of Participants Who Discontinued Study Drug Due to an AE

  An AE was defined as 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.

  Up to 56 weeks

Secondary Outcomes (6)

• Mean Percent Change From Baseline in LDL-C at Week 52

  Baseline and Week 52

• Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24

  Baseline and Week 24

• Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24

  Baseline and Week 24

• Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24

  Baseline and Week 24

• Percentage of Participants With LDL-C <70 mg/dL and ≥50% Reduction From Baseline at Week 24

  Baseline and Week 24

Study Arms (2)

Enlicitide Decanoate

EXPERIMENTAL

Participants received 20 mg of enlicitide decanoate orally once daily (QD) for up to 52 weeks.

Drug: Enlicitide Decanoate

Placebo

PLACEBO COMPARATOR

Participants received enlicitide decanoate-matching placebo orally QD for up to 52 weeks.

Drug: Placebo

Interventions

Placebo DRUG

Oral tablet (placebo).

Placebo

Enlicitide Decanoate DRUG

Oral tablet

Also known as: MK-0616

Enlicitide Decanoate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has possible or definite diagnosis of heterozygous familial hypercholesterolemia (HeFH) based on a locally accepted diagnostic algorithm
• Has an LDL-C ≥55 mg/dL or ≥70 mg/dL depending on medical history
• Is treated with a moderate- or high-intensity statin medication
• Is on a stable dose of all background lipid-lowering therapies (LLTs) with no planned medication change

You may not qualify if:

• Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH
• Has a history of heart failure or heart failure hospitalization within 3 months before first study visit
• Is undergoing or previously underwent an LDL-C apheresis program within 3 months before first study visit 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (59)

Alliance for Multispecialty Research, LLC ( Site 0023)

Daphne, Alabama, 36526, United States

Location

Excel Medical Clinical Trials ( Site 0008)

Boca Raton, Florida, 33434, United States

Location

Advanced Pharma Research ( Site 0007)

Cutler Bay, Florida, 33189, United States

Location

Progressive Medical Research ( Site 0021)

Port Orange, Florida, 32127, United States

Location

Clinical Site Partners LLC, dba CSP Orlando ( Site 0028)

Winter Park, Florida, 32789, United States

Location

Synexus Clinical Research US - Evansville ( Site 0031)

Evansville, Indiana, 47714, United States

Location

Franciscan Physician Network - Indiana Heart Physicians ( Site 0040)

Indianapolis, Indiana, 46237, United States

Location

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division ( Site 0001)

Troy, Michigan, 48098, United States

Location

Velocity Clinical Research at The Pioneer Heart Institute, Lincoln ( Site 0026)

Lincoln, Nebraska, 68506, United States

Location

Jubilee Clinical Research ( Site 0030)

Las Vegas, Nevada, 89106, United States

Location

Wake Forest Baptist Health-Cardiovascular Medicine ( Site 0041)

Winston-Salem, North Carolina, 27157, United States

Location

Velocity Clinical Research, Salt Lake City ( Site 0004)

West Jordan, Utah, 84088, United States

Location

Health Research of Hampton Roads, Inc. ( Site 0020)

Newport News, Virginia, 23606, United States

Location

Royal Prince Alfred Hospital-6West CV Ambulatory Care ( Site 2808)

Camperdown, New South Wales, 2050, Australia

Location

Victorian Heart Hospital-Monash Cardiovascular Research Centre (MCRC) ( Site 2803)

Clayton, Victoria, 3168, Australia

Location

Universidade Federal Do Ceara ( Site 0702)

Fortaleza, Ceará, 60430-270, Brazil

Location

Instituto Dante Pazzanese de Cardiology-Fundação Adib Jatene ( Site 0701)

São Paulo, São Paulo, 04012-909, Brazil

Location

Incor - Instituto do Coracao ( Site 0703)

São Paulo, 05403-000, Brazil

Location

Ecogene-21 ( Site 0510)

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Institut de Cardiologie de Montreal ( Site 0506)

Montreal, Quebec, H1T 1C8, Canada

Location

Diex Recherche Trois-Rivieres ( Site 0513)

Trois-Rivières, Quebec, G9A 4P3, Canada

Location

Clinical Research Chile SpA ( Site 0804)

Valdivia, Los Ríos Region, 5110683, Chile

Location

CDIEM ( Site 0814)

Providencia, Region M. de Santiago, 7500859, Chile

Location

Enroll SpA ( Site 0803)

Santiago, Region M. de Santiago, 7500587, Chile

Location

Pontificia Universidad Catolica de Chile-CICUC ( Site 0812)

Santiago, Region M. de Santiago, 8330034, Chile

Location

Fundación Centro de Investigación Clínica CIC ( Site 0906)

Medellín, Antioquia, 050021, Colombia

Location

Ciensalud Ips S A S ( Site 0903)

Barranquilla, Atlántico, 08001, Colombia

Location

Clinica de la Costa S.A.S. ( Site 0902)

Barranquilla, Atlántico, 080020, Colombia

Location

Salud SURA Calle 100 ( Site 0918)

Bogotá, Cundinamarca, 110231, Colombia

Location

Fakultní nemocnice Brno Bohunice-Interni kardiologicka klinika ( Site 3602)

Brno, Brno-mesto, 625 00, Czechia

Location

Institut Klinicke a Experimentalni Mediciny ( Site 3601)

Prague, Praha 4, 140 21, Czechia

Location

Fakultni Nemocnice u sv. Anny v Brne ( Site 3604)

Brno, South Moravian, 60200, Czechia

Location

Meilahden tornisairaala - Meilahti Tower Hospital ( Site 1300)

Helsinki, Uusimaa, 00290, Finland

Location

Queen Mary Hospital-Medical ( Site 3300)

Pok Fu Lam, Hong Kong

Location

Prince of Wales Hospital ( Site 3304)

Shatin, NT, Hong Kong

Location

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Belgyógyászati Klinika ( Site 1603)

Szeged, Csongrád megye, 6725, Hungary

Location

Semmelweis Egyetem-Városmajori Szív- és Érgyógyászati Klinika ( Site 1600)

Budapest, 1122, Hungary

Location

Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Anyagcsere Tanszék) ( Site 1601)

Debrecen, 4032, Hungary

Location

Shaare Zedek Medical Center ( Site 1710)

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center ( Site 1709)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center ( Site 1717)

Petah Tikva, 4941492, Israel

Location

Clalit Health Services - Sakhnin Community Clinic-Research Unit ( Site 1700)

Sakhnin, 308100, Israel

Location

Radboudumc-internal medicine ( Site 1952)

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Amsterdam UMC, locatie AMC-Vascular Medicine Clin Trial Unit ( Site 1954)

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Vasculair Onderzoek Centrum Hoorn ( Site 1953)

Hoorn, North Holland, 1625 HV, Netherlands

Location

Universitair Medisch Centrum Utrecht-Vascular Medicine Research ( Site 1955)

Utrecht, 3584 CX, Netherlands

Location

Pacific Clinical Research Network - Rotorua ( Site 2902)

Rotorua, Bay of Plenty, 3010, New Zealand

Location

New Zealand Clinical Research (Christchurch) ( Site 2901)

Christchurch, Canterbury, 8011, New Zealand

Location

Nordlandssykehuset ( Site 2001)

Bodø, Nordland, 8005, Norway

Location

Oslo Universitetssykehus Aker-Lipidklinikken ( Site 2000)

Oslo, 0316, Norway

Location

National University Hospital-Department of Medicine ( Site 3212)

Singapore, Central Singapore, 119074, Singapore

Location

Changi General Hospital ( Site 3211)

Singapore, Central Singapore, 529889, Singapore

Location

Hospital de Sant Joan Despí Moisès Broggi ( Site 2335)

Sant Joan Despí, Catalonia, 08970, Spain

Location

SALUT SANT JOAN DE REUS-BAIX CAMP (EDP)-Vascular and Metabolism Unit ( Site 2329)

Reus, Tarragona, 43204, Spain

Location

HOSPITAL CLINICO DE VALENCIA ( Site 2321)

Valencia, Valenciana, Comunitat, 46010, Spain

Location

Mackay Memorial Hospital -Tamshui Branch ( Site 3109)

New Taipei City, New Taipei, 251, Taiwan

Location

Shin Kong Wu Ho-Su Memorial Hospital ( Site 3106)

Taipei City, Taipei, 111, Taiwan

Location

National Cheng Kung University Hospital-Internal Medicine ( Site 3107)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 3100)

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Ballantyne CM, Gellis L, Tardif JC, Banka P, Navar AM, Asprusten EA, Scott R, Stroes ESG, Froman S, Mendizabal G, Wang F, Catapano AL. Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA. 2026 Jan 13;335(2):129-139. doi: 10.1001/jama.2025.20620.

  PMID: 41206969 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipoproteinemia Type II

Interventions

MK-0616

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: July 19, 2023
• Study Start: August 8, 2023
• Primary Completion: April 7, 2025
• Study Completion: April 7, 2025
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

NL (4); CL (4); NO (2); FI (1); SG (2); IL (4); HK (2); TW (4); CZ (3); US (13); BR (3); CO (4); AU (2); CA (3); NZ (2); HU (3); ES (3)