VERVE-102 for High Cholesterol

Recruiting at 13 trial locations

Overseen By Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Verve Therapeutics, Inc.

Must not be taking: PCSK9 inhibitors

Disqualifiers: Chronic liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called VERVE-102, designed to help people with high cholesterol. It targets individuals with conditions like heterozygous familial hypercholesterolemia (a genetic disorder causing high cholesterol) or premature coronary artery disease (early heart artery problems) who need additional help lowering their LDL cholesterol (often called "bad" cholesterol). The study will assess the safety of VERVE-102 and its effects on the body. People diagnosed with these conditions and not currently treated with certain cholesterol medications might be suitable candidates. Participants will receive a single dose of the treatment to observe its effects. As a Phase 1 trial, this research focuses on understanding how VERVE-102 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you are not currently being treated with a PCSK9 inhibitor or have not been treated with one recently. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that VERVE-102 is likely to be safe for humans?

Research has shown that VERVE-102 has been tested in people with promising safety results. Early findings from past studies indicate that a single dose of VERVE-102 significantly lowered LDL cholesterol, often known as "bad" cholesterol, without causing serious side effects. These studies found that higher doses led to greater reductions in cholesterol, suggesting the treatment is well-tolerated even at increased doses.

The treatment uses a technology that targets the PCSK9 gene, which helps control cholesterol levels. The main focus is on ensuring safety and understanding how the treatment works in the body. Current results are encouraging, showing no major negative effects linked to the treatment. This suggests that VERVE-102 is safe to use, at least in the short term, based on the data available so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, which often include statins and lifestyle changes, VERVE-102 is unique because it targets the genetic root of the condition. Researchers are excited about VERVE-102 because it uses a gene-editing approach to potentially make long-lasting reductions in LDL cholesterol levels with just a single dose. This innovative mechanism could offer a more permanent solution compared to ongoing medication regimens, revolutionizing how high cholesterol is managed.

What evidence suggests that VERVE-102 might be an effective treatment for high cholesterol?

Research has shown that VERVE-102 can effectively lower cholesterol levels. Studies have found that just one dose of VERVE-102 significantly reduces levels of the protein PCSK9 and LDL-C, often referred to as "bad cholesterol." Results indicate that higher doses lead to greater reductions. In animal studies, a single treatment led to an 80% drop in PCSK9 and a 62% drop in LDL-C. These findings suggest that VERVE-102 could be a strong option for managing high cholesterol by targeting the PCSK9 gene in the liver. Participants in this trial will receive a single dose of VERVE-102 as part of a dose escalation study to further evaluate its effectiveness and safety. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with familial hypercholesterolemia or premature coronary artery disease who need extra help lowering their LDL cholesterol. It's open to men and women who can't have children.

Inclusion Criteria

I have been diagnosed with familial hypercholesterolemia or early-onset coronary artery disease.

I am either a male or a female who cannot become pregnant.

Exclusion Criteria

I have a genetic condition that causes very high cholesterol.

Clinically significant or abnormal laboratory values as defined by the protocol

I have or had liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single ascending dose of VERVE-102 to evaluate safety and pharmacodynamics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after receiving the dose

12 weeks

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• VERVE-102

Trial Overview VERVE-102, a new treatment using base-editing technology, is being tested. It aims to disrupt the PCSK9 gene in the liver, which should lower bad cholesterol levels. This early-phase study will check its safety and how it affects patients.

How Is the Trial Designed?

Group I: Cohort 6: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Group II: Cohort 5: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Group III: Cohort 4: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Group IV: Cohort 3: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Group V: Cohort 2: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Group VI: Cohort 1: Single Ascending Dose Escalation Experimental Treatment 1 Intervention

Participants will receive a single dose of VERVE-102.

Who Is Running the Clinical Trial?

Verve Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

230+

Published Research Related to This Trial

Despite the effectiveness of statin therapy in lowering LDL cholesterol and reducing cardiovascular events, there remains a significant residual risk of cardiac events, particularly in high-risk patients, indicating the need to explore additional risk factors beyond LDL.

Elevated levels of high-density lipoprotein (HDL) cholesterol are associated with protective effects against atherosclerosis, and low HDL levels are independent predictors of cardiovascular risk, suggesting that therapies aimed at raising HDL could further reduce cardiac risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low high-density lipoprotein cholesterol: current status and future strategies for management. Singh, V., Sharma, R., Kumar, A., et al.[2021]

The VA-HIT trial showed that gemfibrozil treatment significantly reduces the risk of major coronary events by 22% and cardiovascular events by 24% in men with coronary heart disease and low HDL cholesterol levels.

Gemfibrozil works by increasing HDL cholesterol levels by 6% and decreasing triglyceride levels by 31%, while not affecting LDL cholesterol concentrations, making it an effective option for secondary prevention in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of the month. Usefulness of increasing HDL cholesterol in secondary prevention of coronary heart disease: results of the VA-HIT study]. Scheen, AJ.[2015]

In Tayside, Scotland, only 7.9% of Type 1 diabetes patients and 18.3% of Type 2 diabetes patients with macrovascular disease were using lipid-lowering therapy, indicating a significant gap in treatment for those who need it.

Factors such as being a current or former smoker and having a history of coronary heart disease increased the likelihood of using lipid-lowering therapy, while older age (over 70 years) decreased the likelihood, highlighting the need for targeted interventions in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment gap in the use of lipid-lowering drug therapy in diabetes: a population-based study. James, P., Tan, HH., MacAlpine, R., et al.[2010]

Lowering LDL cholesterol levels with statins has been shown to reduce recurrent cardiovascular events by nearly 25%, highlighting their efficacy in managing hyperlipidemia and preventing atherosclerotic disease.

First-line treatment for patients with atherosclerotic vascular disease includes statins and lifestyle changes, while second-line options like fibrates and ezetimibe can be used to further lower cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approach to lipid therapy in the patient with atherosclerotic vascular disease. Pande, RL.[2021]

Reducing low-density lipoprotein cholesterol (LDL-chol) is crucial for lowering cardiovascular disease risk, with high-potency statins effectively lowering LDL-chol by 15-30% and improving patient outcomes in both primary and secondary prevention.

Monoclonal antibodies that inhibit the PCSK9 protein can reduce LDL-chol by over 60%, but their high cost limits their use to patients with severe conditions like ischaemia or familial hypercholesterolaemia who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LDL-cholesterol: The lower the better. Pedro-Botet, J., Pintó, X.[2021]

In a study of high-risk patients switched from simvastatin therapy, the combination of ezetimibe/simvastatin led to significantly greater reductions in LDL cholesterol (37 mg/dL) compared to rosuvastatin (25 mg/dL) and atorvastatin (26 mg/dL).

All treatment regimens improved other lipid parameters, such as total cholesterol and triglycerides, with no significant differences in adverse events among the different therapies, indicating a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. Furman, A., Meier, JL., Malmstrom, RA., et al.[2018]

Atherosclerotic vascular disease is a leading cause of death in the U.S., with 13-14 million adults affected by coronary artery disease (CAD), highlighting the critical need for effective cholesterol management.

Statins, a class of drugs that lower LDL cholesterol, have been shown in clinical trials to effectively reduce LDL levels and decrease the risk of coronary events, making them a key treatment for patients with elevated cholesterol and CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials. Eisenberg, DA.[2019]

In a systematic review of 59 trials with over 173,000 participants, statins were found to significantly reduce mortality from coronary heart disease by 34% and all-cause mortality by 25%, making them the most effective cholesterol-lowering intervention.

The effectiveness of statins compared to other cholesterol-lowering drugs is likely due to their greater ability to reduce cholesterol levels, as shown by meta-regression analysis that linked cholesterol reduction to improved mortality outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review on the risk and benefit of different cholesterol-lowering interventions. Bucher, HC., Griffith, LE., Guyatt, GH.[2019]

Statin therapy has been shown to reduce the risk of cardiovascular events in patients with low HDL cholesterol, indicating its efficacy even in those with normal or elevated cholesterol levels.

Recent trials suggest that fibrate therapy may also be beneficial for patients with low HDL, highlighting the potential for various HDL-raising agents to play a role in treating high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of low high-density lipoprotein cholesterol. Miller, M.[2022]

In a study involving 876 Japanese patients with coronary heart disease, adding probucol to standard lipid-lowering therapy showed a trend towards reducing cardiovascular events, despite a decrease in HDL-cholesterol levels.

Probucol's potential benefits may stem from its strong antioxidant properties and its ability to enhance reverse cholesterol transport, although further research is needed to confirm its clinical effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Coronary Heart Disease (PROSPECTIVE). Yamashita, S., Arai, H., Bujo, H., et al.[2021]

Citations

1. vervetx.com vervetx.com/sites/default/files/2025-07/newsarticle-asset-auto-20250414-8921.pdf

Verve Therapeutics Announces Positive Initial Data from ... A single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 protein levels and LDL-C, with a mean reduction in blood. LDL-C of ...

2. tctmd.com tctmd.com/news/topline-data-point-promise-verve-102-gene-editing-therapy

Topline Data Point to Promise for VERVE-102 Gene- ... The new topline data from Heart-2 show that a single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 and LDL levels among ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1933287425001710

VERVE-102, a clinical stage in vivo base editing medicine ... In NHPs, a single infusion of VERVE-102 (3 mg/kg) led to durable mean reductions of 80% and 62% in blood PCSK9 and LDL-C, respectively. Editing efficiency was ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06164730

NCT06164730 | A Study of VERVE-102 in Patients with ... This Study is Designed to Determine the Safety and Pharmacodynamic Profile of VERVE-102 in This Patient Population. Official Title. Open-label, Phase 1b, Single ...

5. vervetx.com vervetx.com/sites/default/files/2025-04/VERV%20Heart-2%20Data%20Call%20Deck_041425_PP%20page.pdf

Initial Data from the Heart-2 Clinical Trial of VERVE-102 What is ASCVD? ASCVD is the leading cause of death in the world. HeFH is the most prevalent genetic disease in humans.

6. vervetrials.com vervetrials.com/

Verve Trials The purpose of the Heart-2 study is to assess the safety and tolerability of the investigational medicine called VERVE-102 and see if it can help lower LDL-C ...

7. statnews.com statnews.com/2025/04/14/verve-102-gene-editing-therapy-cholesterol-phase-1-study-safety/

Verve therapy lowers cholesterol without serious side effects ... Initial Phase 1 data show that a single infusion of Verve-102 led to greater decreases in "bad" LDL cholesterol with higher doses.

8. vervetx.gcs-web.com vervetx.gcs-web.com/news-releases/news-release-details/verve-therapeutics-receives-us-fda-fast-track-designation-verve

Verve Therapeutics Receives U.S. FDA Fast Track ... VERVE-102 is currently being tested in the Phase 1b Heart-2 clinical trial, which is designed to evaluate the safety and tolerability of VERVE- ...