A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)

Phase 2

Completed

• Conditions: Hypercholesterolemia; Familial Hypercholesterolemia
• Interventions: Drug: Enclitide Chloride; Drug: Placebo

• Registration Number: NCT05261126
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-22
• Study First Submitted QC: 2022-02-22
• Study First Posted: 2022-03-02
• Study Start: 2022-03-10
• Primary Completion: 2022-11-28
• Study Completion: 2022-11-28
• Results First Submitted: 2023-11-15
• Results First Submitted QC: 2023-11-15
• Results First Posted: 2023-12-06
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 381

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enclitide Chloride 6 mg	Enclitide Chloride	Participants will receive 6 mg of enlicitide chloride orally QD for 8 weeks
Enclitide Chloride 12 mg	Enclitide Chloride	Participants will receive 12 mg of enlicitide chloride orally QD for 8 weeks
Enclitide Chloride 18 mg	Enclitide Chloride	Participants will receive 18 mg of enlicitide chloride orally QD for 8 weeks
Enclitide Chloride 30 mg	Enclitide Chloride	Participants will receive 30 mg of enlicitide chloride orally QD for 8 weeks
Placebo	Placebo	Participants will receive enlicitide chloride-matching placebo orally QD for 8 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced One or More Adverse Events (AEs)	Up to approximately 17 Weeks	An AE was 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced at least one AE was reported.
Percentage of Participants Who Discontinued Study Intervention Due to AEs	Up to approximately 9 Weeks	An AE was 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to AEs was reported.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 8	Baseline and up to Week 8	Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in LDL-C. Based on a constrained longitudinal analysis (cLDA) model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in LDL-C at week 8 was reported.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 8	Baseline and up to Week 8	Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in ApoB. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in ApoB at week 8 was reported.
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 8	Baseline and up to Week 8	Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in non-HDL-C. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in non-HDL-C at week 8 was reported.
Percentage of Participants With LDL-C Value at Goal at Week 8	Week 8	LDL-C goal was defined as: LDL-C \<70 mg/dL (\<1.81 mmol/L) in participants with clinical atherosclerotic cardiovascular disease (ASCVD), LDL-C \<100 mg/dL (\<2.59 mmol/L) in participants with an ASCVD risk-equivalent and/or a 10-year risk of having an ASCVD event that is ≥7.5%, OR LDL-C \<130 mg/dL (\<3.37mmol/L) in participants with a 10-year risk of having an ASCVD event that is ≥5.0% and \<7.5%. The percentage of participants with LDL-C value at goal at week 8 were reported.

Trial Locations

Locations (63)

Westside Medical Associates of Los Angeles ( Site 0026); 🇺🇸 Beverly Hills, California, United States

Clinical Trials Research ( Site 0007); 🇺🇸 Sacramento, California, United States

National Research Institute (NRI) - Santa Ana ( Site 0024); 🇺🇸 Santa Ana, California, United States

Excel Medical Clinical Trials ( Site 0042); 🇺🇸 Boca Raton, Florida, United States

Alliance for Multispecialty Research, LLC ( Site 0050); 🇺🇸 Coral Gables, Florida, United States

ForCare Clinical Research ( Site 0017); 🇺🇸 Tampa, Florida, United States

Healthcare Research Network - Chicago ( Site 0037); 🇺🇸 Flossmoor, Illinois, United States

Midwest Institute For Clinical Research ( Site 0036); 🇺🇸 Indianapolis, Indiana, United States

Cotton O'Neil Mulvane ( Site 0022); 🇺🇸 Topeka, Kansas, United States

L-MARC Research Center ( Site 0003); 🇺🇸 Louisville, Kentucky, United States

Scroll for more (53 remaining)