Inclisiran for Cardiovascular Disease

(V-INCLUSION Trial)

Not currently recruiting at 24 trial locations

Overseen By Michael Shapiro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must be taking: Statins

Must not be taking: PCSK9 antibodies, Inclisiran

Disqualifiers: Pregnancy, Heart failure, Arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 450

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests inclisiran, a new cholesterol-lowering drug, to determine its effectiveness in helping people with cardiovascular disease manage their cholesterol levels. It specifically targets those struggling to reach their LDL-C (a type of cholesterol) goals, particularly in under-studied groups. Participants will either receive inclisiran alongside their usual care or continue with their usual care alone. Suitable candidates may include individuals with cardiovascular disease or those at high risk, who have been taking statins or cannot tolerate them, and who are part of a minority group or live in a rural area. As a Phase 4 trial, inclisiran is already FDA-approved and proven effective, and this research aims to understand its benefits for a broader range of patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on statin therapy or have documented statin intolerance to participate.

What is the safety track record for inclisiran?

Research shows that inclisiran is generally safe for people. Long-term studies have found it well tolerated by many different patients. Importantly, these studies revealed no new safety issues. This suggests inclisiran is a safe choice for most people. For those considering joining a trial, this information can be comforting. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Inclisiran is unique because it targets a specific mechanism in cholesterol management. While most treatments for cardiovascular disease, like statins, work by reducing cholesterol production in the liver, inclisiran uses small interfering RNA (siRNA) technology to block the production of a protein called PCSK9. This results in lower LDL cholesterol levels in the blood. Researchers are excited about inclisiran because it offers a potentially more effective and long-lasting reduction in cholesterol with just a few doses per year, compared to daily medications.

What is the effectiveness track record for inclisiran in treating cardiovascular disease?

Research has shown that inclisiran, which participants in this trial may receive, can lower LDL cholesterol, often called "bad" cholesterol, by about 50%. This finding is based on results from several studies, including ORION-9, ORION-10, and ORION-11. In these studies, 85% of patients who took inclisiran reached their recommended LDL cholesterol levels within 90 days, compared to only 31% of those on standard treatments. Lowering LDL cholesterol is linked to a reduced risk of major heart problems. Inclisiran works by blocking a protein that helps produce cholesterol, making it a promising option for managing heart disease. Overall, inclisiran effectively lowers cholesterol and reduces the risk of heart disease. ^{1 4 6 7 8}

Who Is on the Research Team?

Neha Pagidipati, MD

Principal Investigator

Duke Clinical Research Institute

Are You a Good Fit for This Trial?

The VictORION-INCLUSION trial is for adults over 18 with cardiovascular disease or at high risk, as noted in their health records. Participants must have LDL cholesterol above certain levels despite being on statins or having a documented intolerance to them. The study focuses on including underrepresented groups such as women, ethnic minorities, and rural residents.

Inclusion Criteria

I meet all the required conditions for the study.

I am willing and able to follow the study's procedures after giving informed consent.

I am currently on statin therapy or have a documented intolerance to it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Randomized, controlled, multicenter, open-label trial comparing inclisiran and usual care versus usual care alone

52 weeks

Visits at Day 90, Day 270, and Day 360

Treatment Part 2

Single arm trial with usual care participants initiating inclisiran at Day 360, with additional doses on Day 450 and Day 630

36 weeks

Doses on Day 360, Day 450, and Day 630

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inclisiran

Trial Overview This trial tests Inclisiran's ability to manage cholesterol in heart disease patients. It uses electronic health records from US Healthcare Systems to quickly identify and treat those at high risk or with diagnosed atherosclerotic cardiovascular disease (ASCVD) to lower LDL-C levels faster.

How Is the Trial Designed?

Group I: Inclisiran Experimental Treatment 1 Intervention

Inclisiran + Usual Care

Group II: Usual Care Active Control 1 Intervention

Usual Care

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?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Novartis Pharmaceuticals

Industry 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

The XLIMUS sirolimus-eluting stent demonstrated a high delivery success rate of 98% in a study involving 200 patients with complex coronary artery lesions, indicating its effectiveness in challenging cases.

The 1-year rate of major adverse cardiac events (MACE) was 9%, suggesting that the XLIMUS SES is not only deliverable but also safe for patients undergoing percutaneous coronary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of the XLIMUS Sirolimus-Eluting Coronary Stent in Very Complex Lesions. Briguori, C., Visconti, G., Donahue, M., et al.[2022]

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]

The Inspiron™ sirolimus-eluting stent (SES) demonstrated a significant reduction in the need for repeat revascularization procedures (0.0% vs. 23.5%) compared to the bare metal stent after 4 years, indicating its efficacy in long-term cardiac outcomes.

There were no occurrences of stent thrombosis in the study population, highlighting the safety of the Inspiron™ SES over the 4-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year clinical follow-up of the first-in-man randomized comparison of a novel sirolimus eluting stent with abluminal biodegradable polymer and ultra-thin strut cobalt-chromium alloy: the INSPIRON-I trial. Oliveira, MD., Ribeiro, EE., Campos, CM., et al.[2020]

The NEVO sirolimus-eluting stent (SES) demonstrated significantly less neointimal proliferation compared to the TAXUS Liberté paclitaxel-eluting stent (PES), resulting in better arterial response and less late lumen area loss after 6 months in a study of 100 patients.

The NEVO SES showed a more uniform distribution of neointimal thickness, indicating a more consistent performance, while the TAXUS PES exhibited greater positive vessel remodeling, suggesting different mechanisms of action between the two stent types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravascular ultrasound results from the NEVO ResElution-I trial: a randomized, blinded comparison of sirolimus-eluting NEVO stents with paclitaxel-eluting TAXUS Liberté stents in de novo native coronary artery lesions. Otake, H., Honda, Y., Courtney, BK., et al.[2016]

Tranilast is being tested in a large multicenter study involving 11,500 patients to see if it can effectively reduce the risk of restenosis after coronary revascularization procedures, with a focus on its mechanisms that inhibit smooth muscle cell proliferation and collagen synthesis.

This study is significant as it aims to confirm previous positive results seen in Japanese populations and assess whether tranilast can also lower clinical events like death and myocardial infarction in a Western population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial. Holmes, D., Fitzgerald, P., Goldberg, S., et al.[2019]

Citations

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

Current usage of inclisiran for cardiovascular diseases Across pivotal trials, including ORION-9, ORION-10, and ORION-11, inclisiran demonstrated LDL-C reductions of approximately 50%, with effects ...

2. novartis.com novartis.com/news/media-releases/novartis-leqvio-shows-statistically-significant-and-clinically-meaningful-early-ldl-c-goal-achievement-less-muscle-pain

Novartis Leqvio® shows statistically significant and ... After 90 days of treatment with Leqvio on top of LLT, 85% of patients achieved their guideline-recommended LDL-C target compared to 31% of those ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03705234

Study Details | NCT03705234 | A Randomized Trial ... Inclisiran is a PCKS9 synthesis inhibitor which has been found to reduce LDL-cholesterol by about 50-60%. ORION-4 will investigate the effects of inclisiran on ...

5. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(22)00353-9/fulltext

Long-term efficacy and safety of inclisiran in patients with ... In the inclisiran-only arm, LDL cholesterol was reduced by 47·5% (95% CI 50·7–44·3) at day 210 and sustained over 1440 days. The 4-year averaged ...

6. 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 ... Nearly 80% (78.4% (95% CI: 76.8, 80.0)) of patients reached their pre-specified LDL-C targets**, and on average, LDL-C levels were reduced by ...

7. 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 ...

8. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.032031

Harnessing RNA Interference for Cholesterol Lowering Long‐term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on ...