Inclisiran + Statins for Coronary Artery Disease
(V-PLAQUE Trial)
Recruiting in Palo Alto (17 mi)
+147 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Novartis Pharmaceuticals
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing inclisiran, an injectable medication, to see if it can reduce plaque in heart arteries of patients with non-obstructive coronary artery disease who have not had previous heart events. Inclisiran works by lowering 'bad' cholesterol levels in the blood.
Do I have to stop taking my current medications for this trial?
The trial does not specify if you need to stop taking your current medications. However, you must be on a stable dose of statin therapy for at least 4 weeks before the trial. If you're not on a maximally tolerated statin, you may need to go through a Statin Optimization Period.
What data supports the idea that Inclisiran + Statins for Coronary Artery Disease is an effective drug?
The available research does not provide specific data on the effectiveness of Inclisiran + Statins for Coronary Artery Disease. Instead, it focuses on other treatments like drug-eluting stents and their benefits in coronary artery conditions. Without direct evidence from the provided studies, we cannot conclude the effectiveness of Inclisiran + Statins for this condition.
12345What safety data exists for Inclisiran + Statins treatment?
Inclisiran has been evaluated in multiple clinical trials, including the ORION trials and earlier phase 1 trials. The safety profile of Inclisiran is similar to placebo, with mild to moderate, transient injection-site reactions being more frequent. No severe adverse effects, safety concerns, or fatalities directly attributable to Inclisiran were reported. It is considered safe and well-tolerated as a lipid-lowering drug.
678910Is the drug Inclisiran a promising treatment for coronary artery disease?
Yes, Inclisiran is a promising drug for coronary artery disease because it can significantly lower bad cholesterol (LDL-C) levels, especially in people who can't reach their cholesterol goals with statins alone. It is convenient because it only needs to be taken twice a year, and it works well with statins to further reduce cholesterol.
79101112Eligibility Criteria
This trial is for adults aged 18-80 with non-obstructive coronary artery disease (NOCAD) and no past heart events. They must be on a stable dose of the highest tolerated statin therapy, have specific LDL cholesterol levels, and confirmed NOCAD via CCTA scans without severe hypertension, liver disease, or history of cardiovascular events.Inclusion Criteria
My heart scan shows significant plaque but good blood flow and no past heart events.
Participants may have already been identified based on certain heart imaging tests showing specific results.
Your cholesterol levels need to meet certain standards when you haven't eaten for a while, depending on whether you are taking statin medication or not.
+4 more
Exclusion Criteria
My heart's pumping ability is significantly reduced.
I have a history of Peripheral Artery Disease.
My kidney function is not normal, as confirmed by a specific test.
+10 more
Participant Groups
The study tests if inclisiran plus maximum tolerated statins can slow down plaque buildup in heart vessels compared to placebo. Participants' plaque levels are measured using CCTA at the start and after 24 months to see if there's any difference between the two groups.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Inclisiran sodiumExperimental Treatment1 Intervention
Subcutaneous injection
Group II: PlaceboPlacebo Group1 Intervention
Subcutaneous injection
Inclisiran is already approved in European Union, United States, China for the following indications:
🇪🇺 Approved in European Union as Leqvio for:
- Primary hypercholesterolemia (heterozygous familial and non-familial)
- Mixed dyslipidemia
🇺🇸 Approved in United States as Leqvio for:
- Heterozygous familial hypercholesterolemia (HeFH)
- Clinical atherosclerotic cardiovascular disease (ASCVD)
- Primary hypercholesterolemia
🇨🇳 Approved in China as Leqvio for:
- Primary hypercholesterolemia (heterozygous familial and non-familial)
- Mixed dyslipidemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Novartis Investigative SiteLa Jolla, CA
Novartis Investigative SiteCanton, OH
Novartis Investigative SitePasadena, TX
R Ins For Heart And Vascular Health .Reno, NV
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. [2016]The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated.
Coronary angioplasty in drug eluting stent era for the treatment of unprotected left main stenosis compared to coronary artery bypass grafting. [2010]Improved outcomes of percutaneous coronary interventions (PCI) with drug-eluting stents (DES) have resulted in their expanded use for left main coronary artery (LMCA) stenosis.
Five-year clinical results of coronary angioplasty with drug-eluting stents. National initiative in strategic innovation, iNOS. [2010]The use of drug-eluting stents (DES) is beneficial in patients undergoing percutaneous coronary intervention (PCI) and there is particular interest in long-term follow-up.
Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. [2022]Improvements in results with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may extend their use in patients with left main coronary artery (LMCA) stenosis.
Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting. [2018]Statins seem to be suitable for restenosis prevention via reduction of smooth muscle cell proliferation, anti-inflammatory effects, and improvement of endothelial function. The aim of the present study was to test the efficacy of an atorvastatin stent coating for restenosis inhibition in the porcine coronary stent model.
Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia. [2022]Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated.
Inclisiran: First Approval. [2021]Inclisiran (Leqvio®; Novartis) is a first-in-class, cholesterol-lowering small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine carbohydrates (GalNAc). Inclisiran received its first approval in December 2020 in the EU for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is intended for use in combination with a statin or a statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol goals with the maximum tolerated statin dose. In patients who are statin-intolerant or for whom a statin is contraindicated, inclisiran can be used alone or in combination with other lipid-lowering therapies. Inclisiran is administered as a twice-yearly subcutaneous injection. This article summarizes the milestones in the development of inclisiran leading to this first approval for primary hypercholesterolaemia or mixed dyslipidaemia.
Can Clinicians Start Prescribing Inclisiran for Hypercholesterolemia Today? A Review of Clinical Studies for Internal Medicine Physicians and Endocrinologists. [2021]The safety profile and efficacy margin of inclisiran as a lipid-lowering drug have been assessed in clinical trials and are underway in subgroups with relevant co-morbidities. This systematic review looks at the clinical trials that have been conducted to comment on its safety and efficacy. The conclusions can serve as a guide for practicing physicians and researchers for following current and future cohorts of patients. PubMed, Cochrane, Embase, Scopus, CINAHL, Web of Science, and Clinicaltrials.gov were searched comprehensively using the terms "Inclisiran", "ALN-PCSsc", and "ALN-PCS" using the Boolean operator "OR" with data cut-off date of June 28, 2020. The outcomes of safety and efficacy were collected and charted for the systematic review. In our study, eight clinical trials were included in the final study: the ORION (1,2,7,9-11) trials and two clinical trials (phase 1 randomized clinical trials) done before ORION trials. Favourable efficacy in terms of LDL levels and PSCK9 levels was observed across all eight clinical trials. No severe adverse effects, safety concerns, or fatalities attributable directly to inclisiran were reported. Therefore, our study results suggest a positive efficacy and safety profile of inclisiran as a lipid-lowering drug in clinical trials.
Inclisiran: A Review in Hypercholesterolemia. [2023]Inclisiran (Leqvio®) is a first-in-class, subcutaneously administered, small interfering RNA (siRNA) that prevents hepatic synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9), thereby decreasing circulating low-density lipoprotein cholesterol (LDL-C). In the EU, inclisiran is indicated in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet. It is intended for use in patients unable to reach LDL-C goals on maximally tolerated statin therapy, with or without other lipid-lowering therapies (LLTs). In patients who are statin intolerant or for whom a statin is contraindicated, it can be used with or without other LLTs. In clinical trials, twice-yearly injections of inclisiran (after initial doses at days 1 and 90) approximately halved LDL-C levels in patients with, or at high risk of developing, atherosclerotic cardiovascular disease (ASCVD) who had hypercholesterolemia, irrespective of whether or not their existing treatment included a statin. The safety and tolerability profile of the drug was similar to placebo, although mild to moderate, transient injection-site adverse reactions were more frequent with inclisiran. Pending confirmation of the expected reduction in cardiovascular (CV) events with inclisiran, it is a valuable additional/alternative antihyperlipidemic agent to a statin, as its infrequent maintenance dosing regimen confers a convenience advantage over other non-statin LLTs.
New Adjunct Therapy for Elevated Lipid Levels. [2023]Inclisiran (Leqvio) has been approved as adjunct therapy, along with diet and statin therapy, to treat adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional reduction in low-density lipoprotein cholesterol despite maximal statin therapy.Inclisiran is administered subcutaneously by a nurse or other health care provider.
A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. [2021]Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol.
The N-Acetylgalactosamine-conjugated small interfering RNA inclisiran can be coadministered safely with atorvastatin in cynomolgus monkeys resulting in additive low-density lipoprotein cholesterol reductions. [2023]Inclisiran, a small interfering RNA, selectively inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis in the liver and has been shown to reduce low-density lipoprotein cholesterol (LDL-C) by ≥50% in patients with hypercholesterolemia receiving maximally tolerated statins. The toxicokinetic, pharmacodynamic, and safety profiles of inclisiran when coadministered with a statin were characterized in cynomolgus monkeys. Six cohorts of monkeys were administered either atorvastatin (40 mg/kg, reduced to 25 mg/kg during the study, daily, oral gavage), inclisiran (300 mg/kg every 28 days, subcutaneous administration), atorvastatin (40/25 mg/kg) and inclisiran combinations (30, 100, or 300 mg/kg), or control vehicles over 85 days followed by 90 days' recovery. Inclisiran and atorvastatin toxicokinetic parameters were similar in cohorts administered either agent alone or in combination. Inclisiran exposure increased in a dose-proportional manner. At Day 86, atorvastatin increased plasma PCSK9 levels four-fold from pretreatment levels but did not significantly lower serum LDL-C levels. Inclisiran (alone or in combination) reduced PCSK9 (mean decrease 66-85%) and LDL-C (mean decrease 65-92%) from pretreatment levels at Day 86; levels were significantly lower than the control group (p ≤ .05) and remained decreased during the 90-day recovery. Coadministration of inclisiran with atorvastatin resulted in greater reductions in LDL-C and total cholesterol compared with either drug alone. No toxicities or adverse effects were observed in any cohort receiving inclisiran, either alone or in combination. In summary, inclisiran significantly inhibited PCSK9 synthesis and decreased LDL-C in cynomolgus monkeys without increasing the risk of adverse effects when coadministered with atorvastatin.