VERVE-201 for High Cholesterol

Recruiting at 10 trial locations

Overseen By Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Verve Therapeutics, Inc.

Must not be taking: Monoclonal antibodies

Disqualifiers: Chronic liver disease, others

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

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 tests a new treatment called VERVE-201, which aims to lower LDL cholesterol, often referred to as "bad" cholesterol. The trial targets individuals with refractory hypercholesterolemia, meaning their high cholesterol levels resist standard treatments. Participants will receive a single dose to assess the treatment's safety and its impact on cholesterol levels. Ideal candidates are those with high cholesterol unresponsive to other treatments and without liver disease. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on a monoclonal antibody targeting ANGPTL3 or have used one recently.

Is there any evidence suggesting that VERVE-201 is likely to be safe for humans?

Research has shown that VERVE-201 was well-tolerated in animal studies with primates. These studies noted only temporary increases in liver-related markers, a common occurrence with treatments using tiny fat particles to deliver drugs. No serious side effects linked to VERVE-201 were reported in these studies.

As this trial is a Phase 1 study, researchers primarily focus on assessing the treatment's safety in humans. This phase typically marks the first step in testing a new treatment in people. While results in animals have been promising, human trials are essential to fully understand how well people tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high cholesterol, which typically include statins and other cholesterol-lowering medications, VERVE-201 is unique because it uses gene-editing technology to target the root cause of high cholesterol. While most treatments work by inhibiting cholesterol production or absorption, VERVE-201 aims to make permanent changes at the genetic level, potentially providing a long-lasting solution with a single dose. Researchers are excited about VERVE-201 because it could dramatically reduce the need for lifelong medication and improve patient adherence by offering a one-time treatment option.

What evidence suggests that VERVE-201 might be an effective treatment for high cholesterol?

Research shows that VERVE-201, which uses advanced gene-editing technology, may effectively lower LDL cholesterol levels. In early studies, treatments like VERVE-201 reduced LDL cholesterol by about 47%. This treatment targets and turns off the ANGPTL3 gene in the liver, crucial for controlling cholesterol. Initial results from similar research suggest it could be a promising option for managing high cholesterol, especially for patients who haven't succeeded with other treatments. Participants in this trial will receive a single dose of VERVE-201 as part of the dose escalation study. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for men and women who cannot bear children and have refractory hypercholesterolemia, which means their high cholesterol levels remain high despite treatment. Participants should not be able to get pregnant because the effects of VERVE-201 on childbearing are unknown.

Inclusion Criteria

My high cholesterol does not improve with treatment.

I am either not able to become pregnant or I am a male.

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-201 to evaluate safety and pharmacodynamics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after receiving the single dose

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VERVE-201

Trial Overview

VERVE-201, a new therapy using base-editing technology, is being tested in this Phase 1b study. It aims to turn off a gene in the liver responsible for high LDL-C (bad cholesterol) levels. The goal is to see if it's safe and how it affects patients' cholesterol.

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-201.

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

Who Is Running the Clinical Trial?

Verve Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

230+

Published Research Related to This Trial

Drug treatments for high cholesterol, such as cholestyramine and gemfibrozil, have been proven effective and safe in reducing coronary artery disease (CAD) events, leading to their widespread use.

Newer medications like lovastatin and simvastatin show great promise in lowering cholesterol levels and are being tested in large clinical trials to determine their effectiveness in preventing CAD events in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lovastatin and simvastatin prevention studies. Jones, PH.[2019]

Aggressive lowering of LDL cholesterol is beneficial for reducing atherosclerotic disease, but achieving recommended levels with standard doses of lipid-lowering agents has been challenging.

Rosuvastatin has been shown in phase III clinical trials to provide significantly greater reductions in LDL cholesterol compared to other statins, making it a promising option for patients with high cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment. Stein, E.[2019]

Fenofibrate effectively lowers triglycerides, total cholesterol, and LDL cholesterol while raising HDL cholesterol, making it a suitable treatment for various types of hyperlipidemia beyond its FDA-approved indications for types IV and V.

The drug is generally well tolerated, with common side effects being digestive, musculoskeletal, and dermatologic, and it has a favorable safety profile when used with low doses of statins, although monitoring for potential muscle-related issues is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Micronized fenofibrate: a new fibric acid hypolipidemic agent. Guay, DR.[2022]

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]

Citations

1.

vervetx.com

vervetx.com/our-programs/verve-201

Verve 201

Mean LDL-C increased from baseline of 55 mg/dL to 458 mg/dL ... After treating with VERVE-201cyn, the following was demonstrated: 60% mean ANGPTL3 editing; 84% ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06451770

NCT06451770 | Phase 1b Study of VERVE-201 in Patients ...

This study is designed to determine the safety and pharmacodynamic profile of VERVE-201 in this patient population.

3.

vervetx.gcs-web.com

vervetx.gcs-web.com/news-releases/news-release-details/verve-therapeutics-announces-pipeline-progress-and-reports-4

Verve Therapeutics Announces Pipeline Progress and ...

Reported positive initial data from the Heart-2 Phase 1b clinical trial of VERVE-102 demonstrating dose-dependent decreases in blood LDL-C ...

4.

atherosclerosis-journal.com

atherosclerosis-journal.com/article/S0021-9150(24)01063-3/fulltext

An investigational in vivo base editing medicine targeting ...

VERVE-201 surrogates achieved significant LDL-C reduction in nonclinical disease models of homozygous FH, including a mean 47% reduction in LDL-cholesterol ...

5.

scge.mcw.edu

scge.mcw.edu/platform/data/clinicalTrials/report/NCT06451770

Phase 1b Study of VERVE-201 in Patients with Refractory ...

This study is designed to determine the safety and pharmacodynamic profile of VERVE-201 in this patient population. Verve Therapeutics, Inc.

6.

vervetrials.com

vervetrials.com/

Verve Trials

The purpose of the Pulse-1 study is to assess the safety and tolerability of the investigational medicine called VERVE-201 and see if it can help lower LDL-C ...