Clinical trial NCT05261126: A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-0616 in Adults With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Familial Hypercholesterolemia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of enclitide chloride, an oral PCSK9 inhibitor, in lowering low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia. The primary hypothesis is that at least one of the four doses of enclitide chloride tested in this study is superior to placebo on percent change from baseline in LDL-C at Week 8.


Eligibility criteria: Inclusion Criteria:

* History of clinical atherosclerotic cardiovascular disease (ASCVD), or has an ASCVD risk equivalent and/or a 10-year risk of having an ASCVD event ≥5.0%, AND has a corresponding LDL-C that falls within the protocol-specified range at screening.
* Treatment with a stable dose of one or more lipid-lowering therapies for ≥30 days before screening, or has not received treatment with any lipid-lowering therapy for ≥30 days before screening.
* A female participant is not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and for at least 8 weeks after the last dose of study intervention.

Exclusion Criteria:

* History of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria.
* History of nephrotic syndrome.
* History of unstable angina, a myocardial infarction, percutaneous transluminal coronary angioplasty, transient ischemic attack, or stroke within 3 months before Screening.
* Has poorly controlled diabetes mellitus, defined as hemoglobin A1C (A1C) ≥9.0% at Screening.
* History of malignancy ≤3 years before screening, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, which have no timeframe limitations relative to screening.
* Currently participating in or has previously participated in an interventional clinical study within 3 months before Screening.
* Has moderate or greater renal insufficiency.

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 8
timeFrame: Baseline and up to Week 8
measure: Percentage of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to approximately 17 Weeks
measure: Percentage of Participants Who Discontinued Study Intervention Due to AEs
timeFrame: Up to approximately 9 Weeks
Secondary outcomes:
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 8
timeFrame: Baseline and up to Week 8
measure: Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 8
timeFrame: Baseline and up to Week 8
measure: Percentage of Participants With LDL-C Value at Goal at Week 8
timeFrame: Week 8
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles ( Site 0026)
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research ( Site 0007)
state: California
city: Santa Ana
country: United States
facility: National Research Institute (NRI) - Santa Ana ( Site 0024)
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials ( Site 0042)
state: Florida
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC ( Site 0050)
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research ( Site 0017)
state: Florida
city: Flossmoor
country: United States
facility: Healthcare Research Network - Chicago ( Site 0037)
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Institute For Clinical Research ( Site 0036)
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Mulvane ( Site 0022)
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center ( Site 0003)
state: Kentucky
city: Jackson
country: United States
facility: The University of Mississippi Medical Center-Clinical Research and Trials Unit ( Site 0028)
state: Mississippi
city: Las Vegas
country: United States
facility: Jubilee Clinical Research ( Site 0047)
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center ( Site 0032)
state: New Mexico
city: New Windsor
country: United States
facility: Mid Hudson Medical Research ( Site 0004)
state: New York
city: Duncansville
country: United States
facility: altoona center for clinical research ( Site 0045)
state: Pennsylvania
city: Fort Mill
country: United States
facility: Piedmont Research Partners ( Site 0005)
state: South Carolina
city: Dallas
country: United States
facility: Dallas Diabetes Research Center ( Site 0012)
state: Texas
city: Houston
country: United States
facility: Center for Cardiometabolic Disease Prevention/Baylor College of Medicine ( Site 0051)
state: Texas
city: San Antonio
country: United States
facility: Northeast Clinical Research of San Antonio ( Site 0014)
state: Texas
city: Richmond
country: United States
facility: National Clinical Research, Inc-research office ( Site 0019)
state: Virginia
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0504)
state: Bayern
city: Nuremberg
country: Germany
facility: Kardiologische Gemeinschaftspraxis ( Site 0502)
state: Bayern
city: Kassel
country: Germany
facility: Ambulantes Herzzentrum Kassel ( Site 0501)
state: Hessen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig ( Site 0500)
state: Sachsen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum ( Site 0505)
city: Nagoya
country: Japan
facility: Chubu Rosal Hospital ( Site 1612)
state: Aichi
city: Kuse-gun Kumiyama-cho
country: Japan
facility: Kyoto Okamoto Memorial Hospital ( Site 1611)
state: Kyoto
city: Osaka-city
country: Japan
facility: Kitada Clinic ( Site 1604)
state: Osaka
city: Suita-shi
country: Japan
facility: Medical Corporation Heishinkai OCROM Clinic ( Site 1600)
state: Osaka
city: Adachi-ku
country: Japan
facility: Seiwa Clinic ( Site 1605)
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: meiwa hospital ( Site 1602)
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Heishinkai Medical Group ToCROM Clinic ( Site 1601)
state: Tokyo
city: Toshimaku
country: Japan
facility: Sekino Hospital ( Site 1603)
state: Tokyo
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital ( Site 1703)
state: Taegu-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1702)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System ( Site 1701)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1700)
city: Ciudad de México
country: Mexico
facility: Bio Investigación AMARC, S.C. ( Site 0204)
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Hospital Angeles Mocel ( Site 0209)
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0212)
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion en Diabetes y Obesidad-Endocrinology ( Site 0205)
state: Jalisco
city: Guadalajara
country: Mexico
facility: Unidad de Investigaci�n Cl�nica Cardiometabolica de Occident-Unidad de Investigación Clínica Cardio
state: Jalisco
city: Monterrey
country: Mexico
facility: Unidad biomedica avanzada monterrey-Clinical Trials ( Site 0200)
state: Nuevo Leon
city: Ciudad Madero
country: Mexico
facility: Centro de Estudios de Investigacion Metabolicos y Cardiovasculares-Subinvestigation ( Site 0201)
state: Tamaulipas
city: Xalapa
country: Mexico
facility: Hospital Angeles Xalapa-Internal Medicine-Cardiology ( Site 0202)
state: Veracruz
city: Merida
country: Mexico
facility: Medical Care and Research SA de CV ( Site 0211)
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Centro de Atención e Investigación Clínica ( Site 0214)
city: Lørenskog
country: Norway
facility: Akershus Universitetssykehus-Hjertemedisinsk Avdeling ( Site 0705)
state: Akershus
city: Bodø
country: Norway
facility: Nordlandssykehuset ( Site 0709)
state: Nordland
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus ( Site 0706)
state: Rogaland
city: Tønsberg
country: Norway
facility: Sykehuset i Vestfold-Hjerteseksjonen ( Site 0703)
state: Vestfold
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Aker-Preventiv kardiologi Aker ( Site 0704)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Rikshospitalet-Kardiologisk avdeling ( Site 0702)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Ullevål-Hjertemedisinsk avdeling, Ullevål ( Site 0701)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Aker-Lipidklinikken ( Site 0700)
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty-Cardilogy Department ( Site 1003)
state: Izmir
city: Ankara
country: Turkey
facility: Hacettepe Universitesi ( Site 1002)
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi University-Cardiology ( Site 1000)
city: London
country: United Kingdom
facility: Royal Free Hospital ( Site 1311)
state: England
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital-Glasgow Clinical Research Facility ( Site 1310)
state: Glasgow City
city: Blackpool
country: United Kingdom
facility: Layton Medical Centre ( Site 1303)
state: Lancashire
city: London
country: United Kingdom
facility: William Harvey Heart Centre ( Site 1308)
state: London, City Of
city: West Midlands
country: United Kingdom
facility: Walsall Manor Hospital ( Site 1309)
state: Walsall
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Ballantyne CM, Banka P, Mendez G, Garcia R, Rosenstock J, Rodgers A, Mendizabal G, Mitchel Y, Catapano AL. Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616. J Am Coll Cardiol. 2023 Apr 25;81(16):1553-1564. doi: 10.1016/j.jacc.2023.02.018. Epub 2023 Mar 6.