Inclisiran for High Cholesterol

(V-PEDS-OLE Trial)

Not currently recruiting at 74 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Inclisiran

Disqualifiers: Uncontrolled disease, Serious condition, others

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

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: Up to 1080 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of inclisiran, a treatment for high cholesterol, specifically in individuals with two types of inherited high cholesterol, known as HeFH and HoFH. It targets those who participated in earlier studies with inclisiran and found it beneficial. Individuals with HeFH or HoFH who completed the ORION-16 or ORION-13 studies without serious issues might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to contribute to the approval of a potentially life-changing treatment.

Do I have to stop taking my current medications for the Inclisiran trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research shows that inclisiran is generally safe for people. Past studies found no new safety issues with long-term use, which is encouraging for potential clinical trial participants. Inclisiran is already approved to lower bad cholesterol in some patients, indicating it has passed safety tests for that purpose. While some individuals might experience mild side effects, previous research suggests the overall safety is strong. For those considering joining a trial, past findings indicate that inclisiran is likely safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inclisiran is unique because it uses a small interfering RNA (siRNA) mechanism to lower high cholesterol by targeting the PCSK9 protein, which plays a role in regulating cholesterol levels. This approach is different from standard treatments like statins, which work by inhibiting an enzyme involved in cholesterol production. Inclisiran's siRNA method allows for less frequent dosing, potentially just twice a year, offering convenience and potentially better adherence compared to daily medications. Researchers are excited about inclisiran because it represents a novel way to manage cholesterol, possibly providing an option for those who struggle with conventional treatments.

What evidence suggests that inclisiran might be an effective treatment for high cholesterol?

Research shows that inclisiran, the investigational treatment in this trial, can significantly lower LDL cholesterol, often called "bad" cholesterol, which is linked to heart disease. Studies have found that inclisiran reduces LDL cholesterol levels by about 50% on average, typically with just two doses a year. However, inclisiran is less effective for individuals with homozygous familial hypercholesterolemia (HoFH), a rare inherited condition. In these cases, inclisiran lowers a protein called PCSK9 but does not reduce LDL cholesterol. Overall, inclisiran works well for many people with high cholesterol, particularly those with heterozygous familial hypercholesterolemia (HeFH). ^{5 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for men and women who have a condition called HeFH or HoFH, which are types of high cholesterol, and have already been part of the ORION-16 or ORION-13 studies. They should have seen benefits from taking inclisiran previously without serious safety issues.

Inclusion Criteria

People who were part of the ORION-16 or ORION-13 studies and have been diagnosed with HeFH or HoFH.

Your doctor believes that you benefited from taking inclisiran in the ORION-16 or ORION-13 studies.

Exclusion Criteria

Any uncontrolled or serious disease, or any medical, physical, or surgical condition, that may either interfere with participation in the clinical study or interpretation of clinical study results, and/or put the participant at significant risk

I was previously in ORION-16 or ORION-13 studies but had to stop due to serious side effects or other reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inclisiran sodium 300mg in an open-label extension to evaluate long-term safety and tolerability

Up to 1080 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inclisiran

Trial Overview The study is testing the long-term safety and how well people can tolerate inclisiran, a medication for lowering cholesterol levels in patients with HeFH or HoFH who completed prior related studies.

How Is the Trial Designed?

Group I: Inclisiran Experimental Treatment 1 Intervention

Inclisiran sodium 300mg (equivalent to 284mg inclisiran\*) in 1.5mL solution

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

Acitretin is a non-immunosuppressive oral medication that has been used for treating psoriasis, providing efficacy without the risks associated with immunosuppressive therapies.

Tofacitinib, an oral Janus kinase inhibitor, also shows effectiveness in psoriasis treatment but comes with significant safety concerns, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small Molecules for Psoriasis. Leonardi, CL.[2016]

In a study of 22 patients treated with acitretin for psoriasis, gemfibrozil significantly reduced high triglyceride levels associated with retinoid treatment, indicating its efficacy in managing hyperlipidemia (p < 0.01).

Gemfibrozil did not adversely affect the effectiveness of acitretin or cause additional side effects, suggesting it is a safe option for patients experiencing retinoid-induced hyperlipidemia that does not respond to diet changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of gemfibrozil (Lopid) on hyperlipidemia in acitretin-treated patients. Results of a double-blind cross-over study. Vahlquist, C., Olsson, AG., Lindholm, A., et al.[2019]

Acitretin is a valuable treatment option for psoriasis, effective both alone and in combination with other therapies, due to its long-term efficacy and lack of direct immunosuppressive effects.

The consensus guidelines from the Spanish Academy of Dermatology provide comprehensive information on the safe use of acitretin, including its pharmacological properties, indications, contraindications, and treatment strategies for clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Carretero, G., Ribera, M., Belinchón, I., et al.[2022]

In a pilot study of nine patients with severe chronic hand dermatitis (CHD), acitretin showed promising results, with 33.3% of patients achieving a physician global assessment (PGA) of clear or almost clear skin after treatment.

The study found a significant reduction in symptoms, with a 45% decrease in the modified total lesion symptom score (mTLSS), indicating that acitretin may be an effective treatment option for severe CHD, although further research is needed to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label exploratory study of acitretin for the treatment of severe chronic hand dermatitis. Tan, J., Maari, C., Nigen, S., et al.[2018]

Acitretin is a non-immunosuppressive oral medication that has been used for treating psoriasis, indicating it may have a safer profile compared to immunosuppressive treatments.

Tofacitinib, an oral Janus kinase inhibitor, also shows efficacy in psoriasis treatment but comes with significant safety risks, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small Molecules for Psoriasis. Leonardi, CL.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907238/

Safety and Efficacy of Inclisiran in Hyperlipidemia Our pooled analysis demonstrated that inclisiran was associated with a significant decline in the % of LDL‐C levels (MD = −50.42, 95% CI: −56.15 ...

2. 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 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1913805

Inclisiran for the Treatment of Heterozygous Familial ... The reduction in LDL cholesterol levels of almost 50% with twice-yearly administration of inclisiran in patients with heterozygous familial hypercholesterolemia ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.063460

Results From the ORION-5 Randomized Clinical Trial Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels.

5. 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 ...

6. leqviohcp.com leqviohcp.com/safety

well-tolerated safety profile 1 - LEQVIO® (inclisiran) | HCP Review the safety profile of LEQVIO. Access information about adverse reactions and review long-term safety data. See full Prescribing and Safety Info.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK595412/

Inclisiran (Leqvio) - NCBI Bookshelf - NIH Heterozygous familial hypercholesterolemia is a genetic disease that causes high cholesterol. ... safety data for inclisiran. Go to: Economic Evidence. Table 1.

8. 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 ...

9. leqvio.com leqvio.com/

Cholesterol-Lowering Injection | LEQVIO® (inclisiran) Learn about LEQVIO, a twice-yearly injection treatment that may help lower bad cholesterol (LDL-C) in certain patients. See full Prescribing and Safety ...