Inclisiran + Statins for Coronary Artery Disease

(V-PLAQUE Trial)

Not currently recruiting at 161 trial locations

Overseen By Cara East

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Statins

Disqualifiers: Cardiovascular events, Cerebrovascular events, PAD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if inclisiran, when combined with statins, can reduce plaque buildup in the heart's arteries for individuals with non-obstructive coronary artery disease (NOCAD). Participants will receive either inclisiran or a placebo (a treatment with no active medication) to assess inclisiran's effectiveness. The trial seeks individuals with NOCAD, meaning their arteries are less than 50% blocked, and who have not experienced heart-related events like a heart attack. Participants should be on a stable dose of statins or need to start taking them as part of the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require participants to be on a stable dose of statin medication for at least 4 weeks before starting. If you're not on a maximally tolerated statin, you may need to adjust your statin therapy during the study.

Is there any evidence suggesting that inclisiran is likely to be safe for humans?

Research has shown that inclisiran is generally safe for long-term use. Studies lasting over six years consistently found no new safety issues with inclisiran, indicating its usual safety for patients. Long-term use did not lead to unexpected side effects, supporting its role in managing cholesterol levels. While inclisiran effectively lowers LDL-C (bad cholesterol), evidence on its impact on heart disease outcomes, such as heart attacks, remains limited. However, its approval for other high cholesterol conditions further supports its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for coronary artery disease?

Unlike the standard of care for coronary artery disease, which typically includes statins, Inclisiran offers a new approach by targeting the PCSK9 pathway. This pathway helps regulate cholesterol levels in the blood, and Inclisiran works by reducing the production of PCSK9, thereby lowering LDL cholesterol more effectively. Additionally, Inclisiran is administered via a subcutaneous injection just twice a year, which could improve patient adherence compared to daily statin pills. Researchers are excited because this could mean better cholesterol management with fewer doses.

What evidence suggests that inclisiran might be an effective treatment for coronary artery disease?

Research shows that inclisiran, one of the treatments in this trial, helps lower LDL-C, often called "bad cholesterol." It works effectively with statins, common drugs used to lower cholesterol. Although inclisiran reduces cholesterol, limited evidence exists that it directly prevents heart attacks or strokes. However, lowering LDL-C is generally linked to a reduced risk of heart issues. This connection makes inclisiran a promising option for reducing plaque in heart vessels, which this study focuses on. Participants in this trial will receive either inclisiran or a placebo to evaluate its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inclisiran or placebo in addition to maximally tolerated statin therapy

24 months

Regular visits for subcutaneous injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inclisiran
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Inclisiran sodium Experimental Treatment 1 Intervention

Subcutaneous injection

Group II: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Inclisiran (Leqvio) is an approved treatment for adults with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease, specifically for those who still need to lower their LDL cholesterol levels despite being on maximum statin therapy.

This medication is given as a subcutaneous injection by a healthcare provider, making it a convenient option for patients needing additional cholesterol management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjunct Therapy for Elevated Lipid Levels. Aschenbrenner, DS.[2023]

Inclisiran is a novel siRNA therapy that significantly reduces LDL cholesterol levels by approximately 50% with just two injections per year, making it a convenient option for patients with high cholesterol who struggle to meet their goals on statins.

The safety profile of inclisiran is comparable to placebo, with only mild to moderate injection-site reactions being more common, indicating it is generally well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclisiran: A Review in Hypercholesterolemia. Frampton, JE.[2023]

In a study of 84 patients with 89 coronary lesions, pemirolast significantly reduced the rate of restenosis after stent placement, with rates of 15.0% in the pemirolast group compared to 34.1% in the control group.

Pemirolast treatment resulted in a larger lumen cross-sectional area and smaller neointima area, suggesting it may prevent restenosis by inhibiting neointimal hyperplasia, which is the growth of tissue that can block the artery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. Ohsawa, H., Noike, H., Kanai, M., et al.[2016]

Inclisiran, an RNA interference therapy, was found to significantly reduce levels of PCSK9 and LDL cholesterol in healthy volunteers, with reductions maintained for at least 6 months after doses of 300 mg or more.

The treatment was well-tolerated, with only mild to moderate adverse events reported and no serious adverse events, indicating a favorable safety profile for inclisiran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. Fitzgerald, K., White, S., Borodovsky, A., et al.[2021]

Inclisiran effectively reduces low-density lipoprotein cholesterol (LDL-C) levels by 65-92% and significantly inhibits PCSK9 synthesis in cynomolgus monkeys, demonstrating its potential as a powerful treatment for hypercholesterolemia.

The combination of inclisiran with atorvastatin leads to greater reductions in LDL-C and total cholesterol compared to either drug alone, and inclisiran was found to be safe with no observed toxicities or adverse effects during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lehoux, D., Kallend, D., Wijngaard, PLJ., et al.[2023]

In a study involving 10 domestic pigs, atorvastatin-coated stents did not significantly reduce neointimal formation compared to uncoated stents after 28 days, indicating limited efficacy in preventing restenosis.

However, there was a trend towards reduced local inflammation in the atorvastatin stent group, suggesting potential benefits in inflammatory response despite no significant impact on restenosis rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting. Scheller, B., Schmitt, A., Böhm, M., et al.[2018]

This study analyzed the early use of drug-eluting stents (DES) in 1833 patients undergoing percutaneous coronary intervention (PCI) in Portugal in 2003, finding that 19.1% experienced major adverse cardiac events (MACE) over a 5-year follow-up period.

The results showed that the clinical outcomes of DES use in this cohort were comparable to international registries, indicating that DES can be an effective option for patients with coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year clinical results of coronary angioplasty with drug-eluting stents. National initiative in strategic innovation, iNOS. Baptista, J., Teles, RC., da Silva, PC., et al.[2010]

Inclisiran is a novel cholesterol-lowering treatment that works by using small interfering RNA (siRNA) technology, and it was first approved in December 2020 for adults with high cholesterol conditions.

It is administered as a subcutaneous injection twice a year and can be used alone or alongside statins and other lipid-lowering therapies, making it a flexible option for patients who struggle to meet cholesterol goals with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclisiran: First Approval. Lamb, YN.[2021]

In a study of 287 patients with unprotected left main coronary artery (LMCA) stenosis, those treated with drug-eluting stents (DES) had a 1-year mortality rate of 4%, compared to 11% for those who underwent coronary artery bypass grafting (CABG), indicating that PCI with DES can be a safe option for selected patients.

The study found that after the first month, mortality rates between PCI and CABG were not significantly different, suggesting that PCI with DES offers comparable short- and midterm outcomes to CABG for treating LMCA stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary angioplasty in drug eluting stent era for the treatment of unprotected left main stenosis compared to coronary artery bypass grafting. Mäkikallio, TH., Niemelä, M., Kervinen, K., et al.[2010]

Inclisiran is an effective treatment for dyslipidemia, significantly lowering LDL cholesterol (LDL-C) levels through a novel mechanism that silences the PCSK9 gene, as demonstrated in clinical trials from the ORION program.

The safety profile of inclisiran is favorable, with adverse events similar to placebo, although injection-site reactions were more common; this suggests it is a well-tolerated option for patients compared to other PCSK9 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia. Banerjee, Y., Pantea Stoian, A., Cicero, AFG., et al.[2022]

In a study of 249 patients with left main coronary artery stenosis, there was no significant difference in mortality rates between those treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES) and those who underwent coronary artery bypass grafting (CABG) after one year.

However, PCI with DES was associated with a lower occurrence of combined adverse events, including death and myocardial infarction, suggesting it may offer some benefits in terms of safety compared to CABG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. Chieffo, A., Morici, N., Maisano, F., et al.[2022]

Inclisiran has demonstrated favorable efficacy in lowering LDL cholesterol and PSCK9 levels across eight clinical trials, indicating its effectiveness as a lipid-lowering drug.

The safety profile of inclisiran is positive, with no severe adverse effects or fatalities reported, suggesting it is a safe option for patients needing cholesterol management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Clinicians Start Prescribing Inclisiran for Hypercholesterolemia Today? A Review of Clinical Studies for Internal Medicine Physicians and Endocrinologists. Jahangir, A., Sahra, S., Krzyzak, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11868277/

Current usage of inclisiran for cardiovascular diseases Although the studies showed inclisiran to lower LDL-C effectively, the evidence is still limited with regards to cardiovascular outcomes data.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667089525000264

Inclisiran for fast-track lipid-lowering treatment early after ... Inclisiran is safe and effective in lowering LDL-C in patients with familial heterozygous hypercholesterolaemia, patients at high cardiovascular risk and ...

3. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4139801

Abstract 4139801: Predicted efficacy of Inclisiran compared ... Data quantifying how lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) and comparison ...

4. novartis.com novartis.com/news/media-releases/novartis-presents-new-long-term-leqvio-inclisiran-data-demonstrating-consistent-efficacy-and-safety-beyond-six-years

Novartis presents new long-term Leqvio® (inclisiran) data ... “These long-term results show that twice-yearly inclisiran, when used in addition to statin therapy, provides consistent LDL-C reduction in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03705234

Study Details | NCT03705234 | A Randomized Trial ... The study aims to find out if a new cholesterol-lowering injection (inclisiran) safely lowers the risk of heart attacks and strokes in people who have already ...

6. jacc.org jacc.org/doi/10.1016/j.jacc.2023.10.007

Safety and Tolerability of Inclisiran for Treatment ... Long-term treatment with inclisiran was well tolerated in a diverse population, without new safety signals, supporting the safety of inclisiran in patients ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604817/

Inclisiran (Leqvio) - NCBI Bookshelf - NIH Sample sizes were not determined based on these outcomes, events were captured via the safety population, and definitions may not have been inclusive or ...