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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-0616 in Adults With Heterozygous Familial Hypercholesterolemia.

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia; Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Enlicitide Decanoate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital-6West CV Ambulatory Care ( Site 2808)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Victorian Heart Hospital-Monash Cardiovascular Research Centre (MCRC) ( Site 2803)
• Brazil
  • São Paulo, Brazil, 05403-000
    • Incor - Instituto do Coracao ( Site 0703)
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-270
      • Universidade Federal Do Ceara ( Site 0702)
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04012-909
      • Instituto Dante Pazzanese de Cardiology-Fundação Adib Jatene ( Site 0701)
• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21 ( Site 0510)
    • Montreal, Quebec, Canada, H1T 1C8
      • Institut de Cardiologie de Montreal ( Site 0506)
    • Trois-Rivières, Quebec, Canada, G9A 4P3
      • Diex Recherche Trois-Rivieres ( Site 0513)
• Chile
  • Los Ríos Region
    • Valdivia, Los Ríos Region, Chile, 5110683
      • Clinical Research Chile SpA ( Site 0804)
  • Region M. de Santiago
    • Providencia, Region M. de Santiago, Chile, 7500859
      • CDIEM ( Site 0814)
    • Santiago, Region M. de Santiago, Chile, 7500587
      • Enroll SpA ( Site 0803)
    • Santiago, Region M. de Santiago, Chile, 8330034
      • Pontificia Universidad Catolica de Chile-CICUC ( Site 0812)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050021
      • Fundación Centro de Investigación Clínica CIC ( Site 0906)
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 08001
      • Ciensalud Ips S A S ( Site 0903)
    • Barranquilla, Atlántico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 0902)
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 110231
      • Salud SURA Calle 100 ( Site 0918)
• Czechia
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 625 00
      • Fakultní nemocnice Brno Bohunice-Interni kardiologicka klinika ( Site 3602)
  • Praha 4
    • Prague, Praha 4, Czechia, 140 21
      • Institut Klinicke a Experimentalni Mediciny ( Site 3601)
  • South Moravian
    • Brno, South Moravian, Czechia, 60200
      • Fakultni Nemocnice u sv. Anny v Brne ( Site 3604)
• Finland
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • Meilahden tornisairaala - Meilahti Tower Hospital ( Site 1300)
• Hong Kong
  • Pok Fu Lam, Hong Kong
    • Queen Mary Hospital-Medical ( Site 3300)
  • Shatin, Hong Kong, NT
    • Prince of Wales Hospital ( Site 3304)
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis Egyetem-Városmajori Szív- és Érgyógyászati Klinika ( Site 1600)
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Anyagcsere Tanszék) ( Site 1601)
  • Csongrád megye
    • Szeged, Csongrád megye, Hungary, 6725
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Belgyógyászati Klinika ( Site 1603)
• Israel
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center ( Site 1710)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 1709)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 1717)
  • Sakhnin, Israel, 308100
    • Clalit Health Services - Sakhnin Community Clinic-Research Unit ( Site 1700)
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht-Vascular Medicine Research ( Site 1955)
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboudumc-internal medicine ( Site 1952)
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam UMC, locatie AMC-Vascular Medicine Clin Trial Unit ( Site 1954)
    • Hoorn, North Holland, Netherlands, 1625 HV
      • Vasculair Onderzoek Centrum Hoorn ( Site 1953)
• New Zealand
  • Bay of Plenty
    • Rotorua, Bay of Plenty, New Zealand, 3010
      • Pacific Clinical Research Network - Rotorua ( Site 2902)
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • New Zealand Clinical Research (Christchurch) ( Site 2901)
• Norway
  • Oslo, Norway, 0316
    • Oslo Universitetssykehus Aker-Lipidklinikken ( Site 2000)
  • Nordland
    • Bodø, Nordland, Norway, 8005
      • Nordlandssykehuset ( Site 2001)
• Singapore
  • Central Singapore
    • Singapore, Central Singapore, Singapore, 119074
      • National University Hospital-Department of Medicine ( Site 3212)
    • Singapore, Central Singapore, Singapore, 529889
      • Changi General Hospital ( Site 3211)
• Spain
  • Catalonia
    • Sant Joan Despí, Catalonia, Spain, 08970
      • Hospital de Sant Joan Despí Moisès Broggi ( Site 2335)
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • SALUT SANT JOAN DE REUS-BAIX CAMP (EDP)-Vascular and Metabolism Unit ( Site 2329)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • HOSPITAL CLINICO DE VALENCIA ( Site 2321)
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital-Internal Medicine ( Site 3107)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 3100)
  • New Taipei
    • New Taipei City, New Taipei, Taiwan, 251
      • Mackay Memorial Hospital -Tamshui Branch ( Site 3109)
  • Taipei
    • Taipei City, Taipei, Taiwan, 111
      • Shin Kong Wu Ho-Su Memorial Hospital ( Site 3106)
• United States
  • Alabama
    • Daphne, Alabama, United States, 36526
      • Alliance for Multispecialty Research, LLC ( Site 0023)
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials ( Site 0008)
    • Cutler Bay, Florida, United States, 33189
      • Advanced Pharma Research ( Site 0007)
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research ( Site 0021)
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners LLC, dba CSP Orlando ( Site 0028)
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synexus Clinical Research US - Evansville ( Site 0031)
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Physician Network - Indiana Heart Physicians ( Site 0040)
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division ( Site 0001)
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Velocity Clinical Research at The Pioneer Heart Institute, Lincoln ( Site 0026)
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Jubilee Clinical Research ( Site 0030)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health-Cardiovascular Medicine ( Site 0041)
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City ( Site 0004)
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc. ( Site 0020)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enlicitide Decanoate; Participants received 20 mg of enlicitide decanoate orally once daily (QD) for up to 52 weeks.	Drug: Enlicitide Decanoate; Oral tablet; Other Names: MK-0616
Placebo Comparator: Placebo; Participants received enlicitide decanoate-matching placebo orally QD for up to 52 weeks.	Drug: Placebo; Oral tablet (placebo).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in LDL-C at Week 52	Blood samples were collected at baseline and at Week 52 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 52
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24	Blood samples were collected at baseline and at Week 24 to determine mean percent change in non-HDL-C. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline non-HDL-C as a covariate.	Baseline and Week 24
Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24	Blood samples were collected at baseline and at Week 24 to determine mean percent change in ApoB. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline ApoB as a covariate.	Baseline and Week 24
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24	Blood samples were collected at baseline and at Week 24 to determine percent change in Lp(a). For percent change in Lp(a) at Week 24, the two treatment groups were analyzed using the Wilcoxon signed rank test with Hodges-Lehmann estimation.	Baseline and Week 24
Percentage of Participants With LDL-C <70 mg/dL and ≥50% Reduction From Baseline at Week 24	Blood samples were collected at baseline and at Week 24 to determine the percentage of participants who had LDL-C <70 mg/dL and ≥50% reduction from baseline. The two treatment groups were analyzed based on the Miettinen and Nurminen method for the difference in percentage.	Baseline and Week 24
Percentage of Participants With LDL-C <55 mg/dL and ≥50% Reduction From Baseline at Week 24	Blood samples were collected at baseline and at Week 24 to determine the percentage of participants who had LDL-C <55 mg/dL and ≥50% reduction from baseline. The two treatment groups were analyzed based on the Miettinen and Nurminen method for the difference in percentage.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): April 7, 2025

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypercholesterolemia; Hyperlipoproteinemia Type II; MK-0616
• Other Study ID Numbers: 0616-017; MK-0616-017 (Other Identifier: MSD); U1111-1285-4257 (Registry Identifier: UTN); 2022-502782-14-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No