Inclisiran + Statins for Coronary Artery Disease

(V-PLAQUE Trial)

Recruiting at 149 trial locations

Overseen By Novartis Pharmaceuticals

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

608 Participants Needed

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.

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.

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. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

Is Inclisiran safe for use in humans?

Inclisiran has been shown to be safe and well-tolerated in clinical trials, with no severe adverse effects or safety concerns reported. Mild to moderate reactions at the injection site were more common with inclisiran compared to placebo. ^{6 7 8 9 10}

Is 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. ^{7 9 10 11 12}

How is the drug Inclisiran unique for treating coronary artery disease?

Inclisiran is unique because it is a small interfering RNA (siRNA) drug that lowers cholesterol by blocking the production of a protein called PCSK9, which is different from how traditional statins work. It is administered as a subcutaneous injection only twice a year, offering a convenient dosing schedule compared to other cholesterol-lowering treatments. ^{7 9 10 11 12}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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, 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]

References

1. Netherlands 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. [2016]

2. England 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. [2010]

3. Portugal pubmed.ncbi.nlm.nih.gov

Five-year clinical results of coronary angioplasty with drug-eluting stents. National initiative in strategic innovation, iNOS. [2010]

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

Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Inclisiran: First Approval. [2021]

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

Can Clinicians Start Prescribing Inclisiran for Hypercholesterolemia Today? A Review of Clinical Studies for Internal Medicine Physicians and Endocrinologists. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Inclisiran: A Review in Hypercholesterolemia. [2023]

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

New Adjunct Therapy for Elevated Lipid Levels. [2023]

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

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. [2021]

12. United States 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. [2023]