VERVE-102 for High Cholesterol
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Verve Therapeutics, Inc.
Must not be taking: PCSK9 inhibitors
Disqualifiers: Chronic liver disease, others
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?VT-10201 is an Open-label, Phase 1b, Single-ascending Dose Study That Will Evaluate the Safety of VERVE-102 Administered to Patients With Heterozygous Familial Hypercholesterolemia (HeFH) or Premature Coronary Artery Disease (CAD) Who Require Additional Lowering of LDL-C. VERVE-102 Uses Base-editing Technology Designed to Disrupt the Expression of the PCSK9 Gene in the Liver and Lower Circulating PCSK9 and LDL-C. This Study is Designed to Determine the Safety and Pharmacodynamic Profile of VERVE-102 in This Patient Population.
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.
What data supports the effectiveness of the drug VERVE-102 for high cholesterol?
The research indicates that lowering LDL cholesterol is beneficial in reducing cardiovascular disease risk, and treatments like statins and PCSK9 inhibitors have shown effectiveness in achieving this. While VERVE-102 is not directly mentioned, its effectiveness could be inferred if it functions similarly to these proven cholesterol-lowering drugs.
12345How does the drug VERVE-102 for high cholesterol differ from other treatments?
VERVE-102 is unique because it may target genetic factors contributing to high cholesterol, unlike traditional treatments like statins that primarily focus on lowering LDL cholesterol levels. This approach could offer a novel way to manage cholesterol by addressing underlying genetic causes.
678910Eligibility Criteria
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.
+1 more
Trial Timeline
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)
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Cohort 4: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-102.
Group II: Cohort 3: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-102.
Group III: Cohort 2: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-102.
Group IV: Cohort 1: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-102.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical Study CenterMontreal, Canada
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Who Is Running the Clinical Trial?
Verve Therapeutics, Inc.Lead Sponsor
References
LDL-cholesterol: The lower the better. [2021]The reduction of low density lipoprotein-cholesterol (LDL-chol) has been associated with a decrease in cardiovascular morbidity and mortality. It has been demonstrated that there is no value of LDL-chol below which there ceases to be a preventive benefit with its reduction, and neither has it been observed that there is a higher incidence of secondary effects associated with lower concentrations of LDL-chol. Although there is a wide range of lipid-lowering drugs available, a high percentage of patients do not achieve the desired LDL-chol levels. The high-potency statins reduce the LDL-chol by 15-30%, and can double the percentage of patients that reach their desired level. This combination has shown to be safe and effective in the primary and secondary prevention of cardiovascular disease. Another option is the combination of statins with exchange resins, although this requires a more complex management. The inhibition of PCSK9 protein with monoclonal antibodies reduces the LDL-chol by more than 60%, and is effective in the prevention of cardiovascular disease. However, due to its cost, its use is restricted to patients with ischaemia or familial hypercholesterolaemia that do not achieve the desired levels with conventional drugs. The evidence base as regards the benefit and safety of achieving the desired levels of LDL-chol is very wide and is still increasing. In the next few years, it may be necessary to adjust the intensity of the hypercholesterolaemia treatment to the level of vascular risk of the patients, and to the level of reduction necessary to achieve the therapeutic targets. This will result in a more effective cardiovascular prevention and in a better quality of life, particularly in the large group of patients at higher vascular risk.
Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. [2018]Treatment of dyslipidemia in high-risk patients specifies a low-density lipoprotein (LDL) cholesterol
Systematic review on the risk and benefit of different cholesterol-lowering interventions. [2019]Meta-analyses have investigated the efficacy of cholesterol-lowering interventions in relation to the underlying risk of coronary heart disease and the extent and duration of cholesterol reduction. We systematically reviewed the efficacy of antilipidemic interventions on major mortality outcomes in relation to drug classes. We searched MEDLINE and EMBASE from 1966 through October 1996 for randomized, controlled trials of any cholesterol-lowering interventions reporting mortality data. We included 59 trials involving 85 431 participants in the intervention and 87 729 participants in the control groups. We pooled these trials into 7 pharmacological categories of cholesterol-lowering interventions: statins (13 trials), fibrates (12 trials), resins (8 trials), hormones (8 trials), niacin acid (2 trials), n-3 fatty acids (3 trials), and dietary interventions (16 trials). Of the cholesterol-lowering interventions, only statins showed a large and statistically significant reduction in mortality from coronary heart disease (risk ratio, 0.66; 95% confidence interval [CI], 0.54 to 0. 79) and from all causes (risk ratio, 0.75; 95% CI, 0.65 to 0.86). For both all-cause and cardiovascular mortality, the difference between statins and the combined estimate of the other classes of agents was unlikely to be due to chance (P
New developments in the treatment of low high-density lipoprotein cholesterol. [2022]Reduced levels of high-density lipoprotein (HDL) cholesterol represent an important risk factor for the development and progression of coronary artery disease. In recent years, clinical outcome studies have verified that statin therapy may reduce the risk of initial or recurrent cardiovascular events in subjects with elevated or "normal" cholesterol levels. Subgroup analysis has also revealed that patients with low HDL benefit from this therapy. Two recently presented outcome trials using fibrate therapy also demonstrated a potential role for these medications in subjects with low HDL. The use of various HDL raising agents, singly or in combination on arteriographic progression and their potential mechanisms of action are reviewed. The latter may be an important consideration in the treatment of high-risk patients with low HDL.
Treatment gap in the use of lipid-lowering drug therapy in diabetes: a population-based study. [2010]Lowering cholesterol is highly effective in reducing morbidity and mortality in high-risk people with prevalent cardiovascular disease.
Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Coronary Heart Disease (PROSPECTIVE). [2021]Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD).
Approach to lipid therapy in the patient with atherosclerotic vascular disease. [2021]Hyperlipidemia increases the incidence of atherosclerotic vascular disease and is associated with greater rates of recurrent cardiovascular events among individuals with established vascular disease. Several large population studies have confirmed the link between all cholesterol components (including elevated low-density lipoprotein [LDL] cholesterol, total cholesterol, and triglyceride levels, and reduced high-density lipoprotein [HDL] levels) with coronary heart disease and other manifestations of systemic atherosclerosis. In addition, landmark clinical trials have clearly established that lowering LDL cholesterol levels with statins (HMG-CoA reductase inhibitors) can lower recurrent cardiovascular events by nearly 25%. The benefits of altering non-LDL cholesterol levels (eg, triglycerides and HDL) are less clear, but several other medications are often used in conjunction with statins for cholesterol lowering. First-line therapy for lipid lowering in patients with atherosclerotic vascular disease includes statins and a recommendation for lifestyle changes (including diet and exercise). Second-line options for lowering cholesterol include fibrates, nicotinic acid, bile acid sequestrants, and ezetimibe. Therapeutic goals for patients with vascular disease are to achieve an LDL cholesterol level
Low high-density lipoprotein cholesterol: current status and future strategies for management. [2021]Atherosclerotic cardiovascular disease is the foremost cause of death and disability in the Western world, and it is rapidly becoming so in the developing nations. Even though the use of statin therapy aiming at the low-density lipoprotein cholesterol (LDL) has significantly reduced cardiovascular events and mortality, substantial residual cardiac events still occur in those being treated to the currently recommended targets. In fact, residual risk is also seen in those who are treated "aggressively" such as the "high risk" patients so defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Consequently, one must look for the predictors of risk beyond LDL reduction. High-density lipoprotein cholesterol (HDL) is the next frontier. The protectiveness of elevated HDL against atherosclerosis is well described in the literature. HDL subdues several atherogenic processes, such as oxidation, inflammation, cell proliferation and thrombosis. It also helps mobilize the excess LDL via reverse cholesterol transport. Low levels of HDL have been shown to be independent predictors of risk. Thus, therapies to raise the HDL hold promise for additional cardiac risk reduction. In this regard, several randomized trials have recently tested this hypothesis, especially in patients at high risk. In addition to the use of aggressive lifestyle modification, clinical outcomes have been measured following augmentation of HDL levels with various treatment modalities, including aggressive statin therapy, combination therapy with fibrates and niacin, and direct HDL-raising drug treatments. These data for low HDL as an independent risk factor and as the new treatment target are reviewed in this paper.
Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials. [2019]Atherosclerotic vascular disease is the major cause of death and disability in adult men and women living in the United States, where 13-14 million adults have a history of coronary artery disease (CAD). One-third of the 1.5 million individuals who experience a myocardial infarction (MI) each year will die and one half of these deaths will occur within 60 minutes of the event. The relation between elevated serum lipids and CAD has been corroborated by epidemiologic as well as pathologic evidence. Approximately 96 million people have total cholesterol levels > 200 mg/dL, with 38 million of these individuals having values > 240 mg/ dL. The National Cholesterol Education Program (NCEP) identified elevated low-density lipoprotein (LDL) cholesterol as a primary risk factor for CAD in 1988. This conclusion, along with recommendations for assessment and treatment, was reaffirmed in 1993. The NCEP also recommended that high-risk patients, with or without clinical manifestations of coronary atherosclerosis, should substantially lower their serum cholesterol levels. Specifically, the NCEP recommends that patients with CAD need to maintain serum LDL cholesterol levels of or = 30%. Aggressive dietary and/or drug therapy are recommended to achieve these reductions. In recent years, clinical trials have demonstrated the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") in lowering elevated levels of LDL cholesterol and decreasing the risk for clinical coronary events.
[Clinical study of the month. Usefulness of increasing HDL cholesterol in secondary prevention of coronary heart disease: results of the VA-HIT study]. [2015]The "Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial" (VA-HIT) is a large randomised, double-blind, placebo-controlled clinical trial for the secondary prevention of coronary heart disease. It demonstrates that a fibrate treatment (gemfibrozil) significantly reduces the relative risk of major coronary (-22%, p = 0.006) and cardiovascular (-24%, p