VERVE-201 for High Cholesterol
Recruiting in Palo Alto (17 mi)
+2 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: Monoclonal antibodies
Disqualifiers: Chronic liver disease, others
No Placebo Group
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.
12345Eligibility 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.
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-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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Cohort 4: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-201.
Group II: Cohort 3: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-201.
Group III: Cohort 2: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-201.
Group IV: Cohort 1: Single Ascending Dose EscalationExperimental Treatment1 Intervention
Participants will receive a single dose of VERVE-201.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical Study CenterToronto, Canada
Clinical Study CenterChicoutimi, Canada
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Who Is Running the Clinical Trial?
Verve Therapeutics, Inc.Lead Sponsor
References
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
Micronized fenofibrate: a new fibric acid hypolipidemic agent. [2022]To review the efficacy and safety of fenofibrate in the management of hyperlipidemias.
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.
The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment. [2019]There is considerable evidence that more aggressive lowering of low-density lipoprotein (LDL) cholesterol is associated with increased benefits in reducing atherosclerotic disease burden, supporting the notion of 'the lower, the better.' However, achievement of currently recommended goals has proven difficult with lipid-lowering agents at the commonly used doses. Current options for achieving greater LDL cholesterol reductions include use of high doses of the most effective of the available statins and use of high or moderate statin doses in combination with agents that work in a complementary manner (e.g. bile acid sequestrants or niacin). Near-term options may include statins with increased LDL cholesterol-lowering effectiveness and better-tolerated secondary agents that can be combined with statin therapy. Rosuvastatin (Crestor, AstraZeneca) is a new statin that may prove to be of considerable utility in achieving greater LDL cholesterol reductions than are currently possible with existing statins. Recent phase III clinical trials have shown that this agent produces significantly greater LDL cholesterol reductions than atorvastatin, simvastatin, or pravastatin in patients with primary hypercholesterolemia and significantly greater reductions than the maximal dose of atorvastatin in patients with familial hypercholesterolemia.
Lovastatin and simvastatin prevention studies. [2019]There is substantial evidence that drug treatment of hypercholesterolemia in patients without known coronary artery disease (CAD) can reduce fatal and nonfatal CAD events. Two trials, the Lipid Research Clinics Coronary Primary Prevention Trial and the Helsinki Heart Study used cholestyramine and gemfibrozil, respectively, to alter lipoprotein levels; their demonstrated efficacy and safety have led to their widespread use in hyperlipidemic patients. Recently, a new class of hypolipidemic agents has been shown to be extremely effective in lowering total and low-density lipoprotein cholesterol levels. These drugs, including lovastatin and simvastatin, competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of intracellular cholesterol synthesis. Results of safety and efficacy studies suggest that they may be valuable first-line treatment options for high-risk hypercholesterolemic patients. Two long-term clinical trials are planned with lovastatin and simvastatin. In the United States, lovastatin will be used in a double-blind, placebo-controlled, primary prevention trial involving 8,000 patients without clinical evidence of CAD, slight to moderate elevations of total cholesterol, and low- and high-density lipoprotein cholesterol to establish whether 5 years of treatment will decrease the rate of fatal CAD or nonfatal myocardial infarction. A Scandinavian study of 4,000 patients with ischemic heart disease and hypercholesterolemia will determine if simvastatin will improve total survival and reduce fatal or nonfatal myocardial infarction and sudden death for at least 3 years. These study designs will be discussed and compared with other studies, and the expected impact on CAD event rates presented.