VERVE-201 for High Cholesterol

Recruiting at 3 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

Trial Summary

What is the purpose of this trial?

VT-20101 is an Open-label, Phase 1b, Single-ascending dose study that will evaluate the safety of VERVE-201 administered to patients with Refractory Hypercholesterolemia. VERVE-201 uses base-editing technology designed to inactivate the expression of the ANGPTL3 gene in the liver and lower circulating low-density lipoprotein cholesterol (LDL-C). This study is designed to determine the safety and pharmacodynamic profile of VERVE-201 in this patient population.

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.

What data supports the effectiveness of the drug VERVE-201 for high cholesterol?

The research suggests that lowering LDL cholesterol (the 'bad' cholesterol) is beneficial for heart health, and treatments that significantly reduce LDL cholesterol, like certain statins and PCSK9 inhibitors, have been effective in preventing heart disease. This implies that if VERVE-201 works similarly to these treatments, it could be effective in managing high cholesterol. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

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

Participants will receive a single dose of VERVE-201.

Group IV: 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+

Findings from Research

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]

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]

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]

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]

References

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

Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. [2018]

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

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

3. Spain pubmed.ncbi.nlm.nih.gov

LDL-cholesterol: The lower the better. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Lovastatin and simvastatin prevention studies. [2019]