Oral PCSK9 Inhibitor for High Cholesterol

No longer recruiting at 62 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Statins

Must not be taking: PCSK9 inhibitors

Disqualifiers: Homozygous FH, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well a new oral medication, enlicitide decanoate (a PCSK9 inhibitor), lowers bad cholesterol (low-density lipoprotein cholesterol or LDL-C) in individuals with heterozygous familial hypercholesterolemia, a genetic condition that causes high cholesterol. Researchers seek to determine if this treatment is more effective than a placebo, a pill with no medicine, over 24 weeks. Suitable participants must have a confirmed diagnosis of heterozygous familial hypercholesterolemia, high LDL-C levels, and be on stable doses of cholesterol-lowering medications, such as statins. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on your current cholesterol-lowering medications, including statins, without any planned changes.

Is there any evidence suggesting that enlicitide decanoate is likely to be safe for humans?

Research has shown that enlicitide decanoate, the treatment under study, has promising safety results. In earlier studies, patients with high cholesterol tolerated it well, and no major safety issues emerged. The treatment significantly improved cholesterol levels, indicating it works as intended without causing harm.

Enlicitide decanoate has been tested in other studies and has a good safety record. Most participants did not experience serious side effects. Some common, mild side effects like headaches and mild stomach upset were reported, but these were not severe enough to stop treatment.

Since this trial is in an advanced stage, earlier phases demonstrated the treatment to be generally safe for people. This is a positive sign for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, such as statins, ezetimibe, or injectable PCSK9 inhibitors, MK-0616 is an oral PCSK9 inhibitor. This oral delivery method is a game-changer because it offers a simpler and potentially more convenient way for patients to manage their cholesterol levels compared to injections. Researchers are excited because MK-0616 works by targeting the PCSK9 protein in a new way, which may provide effective cholesterol reduction without the need for frequent doctor visits associated with injectable options. This innovation could make it easier for patients to stick to their treatment plan and improve their overall health outcomes.

What evidence suggests that this treatment might be an effective treatment for high cholesterol?

Research has shown that enlicitide decanoate, which participants in this trial may receive, effectively lowers LDL cholesterol, often referred to as "bad cholesterol." In earlier studies, this pill, a type of PCSK9 inhibitor, led to significant drops in LDL levels. Some studies even reported reductions of over 50%, which is significant for people with high cholesterol. These findings suggest that enlicitide decanoate could effectively manage cholesterol levels. The treatment has demonstrated promise in both safety and effectiveness, making it a strong option for those dealing with high cholesterol issues. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with a condition called heterozygous familial hypercholesterolemia, which causes high cholesterol. Participants must have LDL-C levels above certain thresholds and be on stable doses of statins or other lipid-lowering therapies without plans to change them.

Inclusion Criteria

Your LDL cholesterol level is higher than 55 mg/dL or 70 mg/dL, depending on your medical history.

I have been diagnosed with a type of high cholesterol that runs in families.

I am on a consistent dose of my cholesterol medications with no changes expected.

Exclusion Criteria

I was hospitalized for heart failure or have a history of it within the last 3 months.

I am part of, or plan to join, an LDL cholesterol reduction program.

I have been treated with cholesterol-lowering drugs, including PCSK9 inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 mg of enlicitide decanoate or placebo orally once daily for up to 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-0616

Trial Overview The study tests MK-0616, an oral medication intended to lower 'bad' cholesterol (LDL-C), against a placebo. The main goal is to see if MK-0616 can significantly reduce LDL-C levels after 24 weeks compared to the placebo.

How Is the Trial Designed?

Group I: Enlicitide Decanoate Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 98 older adults prescribed PCSK9 inhibitors, LDL cholesterol levels were significantly reduced by an average of 60% within 6 months, demonstrating the efficacy of this treatment in lowering cholesterol levels.

While PCSK9 inhibitors were generally well-tolerated, with few side effects reported, the high out-of-pocket expenses (OPE) posed a significant barrier to therapy initiation for many patients, highlighting the need for better cost management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Chart Review Evaluating Efficacy, Tolerability, and Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Older Adults. Davis, LE., Pogge, EK.[2021]

PCSK9 is a promising target for lowering LDL cholesterol levels and reducing cardiovascular disease risk, especially since current lipid-lowering medications often increase PCSK9 levels and do not adequately protect all patients from cardiovascular events.

The review discusses various therapeutic strategies under investigation, including antibodies, antisense oligonucleotides, and small interfering RNAs (siRNAs), which aim to inhibit PCSK9 expression and activity, offering new hope for treating hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9: a new target molecule for gene therapy. Banaszewska, A., Piechota, M., Plewa, R.[2021]

A new centralized multidisciplinary clinic successfully initiated PCSK9 inhibitor therapy for 48 out of 100 referred patients, leading to significant reductions in cholesterol levels: total cholesterol decreased by 41% and LDL-C by 58% after 3 months.

The positive outcomes were maintained over 12 months, with LDL-C reductions of 65% and high patient satisfaction, indicating that this model could enhance access and adherence to PCSK9i therapy in other regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative, centralised, multidisciplinary medicines optimisation clinic for PCSK9 inhibitors. Khatib, R., Khan, M., Barrowcliff, A., et al.[2022]

In a study of 1600 patients using PCSK9 inhibitors (PCSK9i) for cholesterol management, nearly half (49.9%) discontinued treatment after 3 years, highlighting a significant challenge in long-term adherence.

Despite the high discontinuation rates, 58% of those who stopped therapy eventually re-initiated treatment, but overall adherence was low, with only 29% maintaining a high level of medication coverage (≥80%), which correlated with lower success in achieving LDL cholesterol targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCSK9 inhibition in clinical practice: Treatment patterns and attainment of lipid goals in a large health maintenance organization. Zafrir, B., Egbaria, A., Stein, N., et al.[2021]

PCSK9 inhibitors significantly reduce the incidence of myocardial infarction by 19% and stroke by 25%, based on a meta-analysis of 81,700 patients, with 41,979 receiving the treatment.

The treatment did not show any effect on mortality rates, indicating that while PCSK9 inhibitors are effective in reducing certain cardiovascular events, they do not impact overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. Cordero, A., Rodríguez-Mañero, M., Fácila, L., et al.[2022]

A large analysis of over 103,000 reports found that PCSK9 inhibitors are associated with increased occurrences of ocular adverse events, particularly increased lacrimation, seasonal allergies, and eye operations, especially in women and individuals over 65 years old.

The study suggests that these ocular adverse events typically occur within 30 days of starting treatment, highlighting the need for monitoring in at-risk populations when prescribing PCSK9 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis. Zhao, X., Wu, J., Zhu, S.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05261126

A Study of the Efficacy and Safety of Enclitide Chloride (MK ... The purpose of this study is to evaluate the efficacy and safety of enclitide chloride, an oral PCSK9 inhibitor, in lowering low-density lipoprotein ...

2. merck.com merck.com/news/merck-announces-positive-topline-results-from-the-first-two-phase-3-coralreef-trials-evaluating-enlicitide-decanoate-for-the-treatment-of-adults-with-hyperlipidemia/

Merck Announces Positive Topline Results From the First ... Enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in both Phase 3 CORALreef HeFH and CORALreef AddOn trials.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11722601/

Emerging oral therapeutic strategies for inhibiting PCSK9 At 8 week follow-up, enlicitide decanoate reduced, in a dose dependent manner, LDL cholesterol by −41.2 %, −55.7 %, −59.1 %, and −60.9 % after ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06008756

Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor ... This is a phase 3, randomized, placebo-controlled study of the efficacy and safety of enlicitide decanoate, an oral proprotein convertase subtilisin/kexin ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-mk-0616-for-adults-with-high-cholesterol/

Study on the Effectiveness and Safety of MK-0616 for ... The study aims to provide valuable information on whether MK-0616 can effectively lower cholesterol levels and improve heart health in individuals with ...

6. merck.com merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/

Merck's Investigational Oral PCSK9 Inhibitor Enlicitide ... Enlicitide is the first oral PCSK9 inhibitor to demonstrate statistically significant and clinically meaningful reductions in LDL-C compared ...