Oral PCSK9 Inhibitor for High Cholesterol

Recruiting at 58 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

303 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called MK-0616 to see if it can lower bad cholesterol levels in adults with a genetic condition that causes very high cholesterol. These patients often need special treatments because regular medications may not work well for them. The study will measure how much MK-0616 can reduce bad cholesterol over several months.

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.

What data supports the effectiveness of the drug MK-0616 for high cholesterol?

Research shows that PCSK9 inhibitors, like MK-0616, are effective in significantly lowering bad cholesterol (LDL-C) levels and improving heart health outcomes. These drugs have been shown to reduce the risk of heart attacks and strokes in people with high cholesterol. ^{1 2 3 4 5}

Is the oral PCSK9 inhibitor safe for humans?

PCSK9 inhibitors, in general, have been shown to have a favorable safety profile in clinical trials, meaning they are generally safe for humans. ^{4 5 6 7 8}

How is the drug MK-0616 different from other treatments for high cholesterol?

MK-0616 is an oral PCSK9 inhibitor, which is unique because it can be taken by mouth, unlike other PCSK9 inhibitors that are usually injected. It works by blocking a protein called PCSK9, which helps lower bad cholesterol (LDL-C) levels in the blood. ^{1 2 4 5 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Proprotein convertase subtilisin/kexin type 9: a new target molecule for gene therapy. [2021]

2. New Zealand 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

PCSK9 inhibition in clinical practice: Treatment patterns and attainment of lipid goals in a large health maintenance organization. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. [2022]

5. Iran pubmed.ncbi.nlm.nih.gov

Application Value of PCSK9 Inhibitor in Cardiovascular High Risk Patients: A Meta-Analysis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

PCSK9 inhibitors in clinical practice: Novel directions and new experiences. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Innovative, centralised, multidisciplinary medicines optimisation clinic for PCSK9 inhibitors. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Advances in the field of proprotein convertase subtilisin kexin type 9 inhibitors. [2018]