Inclisiran for Hypercholesterolemia

(ORION-20 Trial)

Recruiting at 84 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Statins, Ezetimibe

Must not be taking: PCSK9 inhibitors

Disqualifiers: Secondary hypercholesterolemia, HoFH, Active liver disease, 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

Compensation: Varies

Number of Visits: 6

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called inclisiran, a cholesterol-lowering injection, to evaluate its safety and effectiveness for children with heterozygous familial hypercholesterolemia (HeFH), a condition characterized by very high, often inherited, cholesterol levels. The study includes two groups: one receives inclisiran shots, while the other starts with a placebo (a harmless shot) and switches to inclisiran later. Eligible participants have HeFH with high cholesterol levels and have been on stable doses of cholesterol-lowering medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for high cholesterol in children.

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

Participants must be on a stable dose of their current lipid-lowering medications, like statins or ezetimibe, for at least 30 days before the trial and cannot change these medications or doses during the study.

Is there any evidence suggesting that inclisiran is likely to be safe for children with hypercholesterolemia?

Research has shown that inclisiran is generally safe and well-tolerated for treating high cholesterol. Studies have found a higher chance of mild side effects and reactions at the injection site. Inclisiran has been used extensively in adults with cholesterol issues and has demonstrated a good safety record. Notably, the FDA has already approved inclisiran for lowering cholesterol in other conditions, indicating its safety. This information may help prospective trial participants feel more confident about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inclisiran is unique because it uses a novel approach called RNA interference to lower cholesterol. Unlike traditional statins that work by inhibiting an enzyme in the liver, inclisiran targets the production of PCSK9, a protein that degrades receptors responsible for clearing LDL cholesterol from the blood. This mechanism allows for less frequent dosing, with injections needed only a few times a year, offering convenience and potentially better adherence for patients. Researchers are excited about inclisiran because it could significantly improve cholesterol management with a more targeted and sustained effect.

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

Research shows that inclisiran effectively lowers LDL cholesterol, often called "bad" cholesterol, which is linked to heart problems. Studies have found that inclisiran consistently reduces LDL cholesterol levels significantly in people with heterozygous familial hypercholesterolemia (HeFH). This trial will evaluate inclisiran, administered as a subcutaneous injection, to determine if it lowers LDL and other related fats in the blood without increasing the risk of serious side effects. In addition to reducing cholesterol, inclisiran may lower the risk of heart-related issues, such as heart attacks, by about 15%. These findings suggest that inclisiran could be a promising option for managing HeFH in children. ^{1 3 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 children aged 6 to under 12 with heterozygous familial hypercholesterolemia (HeFH) and high LDL cholesterol levels. They must be on a stable dose of lipid-lowering treatments like statins or ezetimibe for at least 30 days before the study, with no changes expected during the trial.

Inclusion Criteria

I am between 6 and 11 years old.

Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening

I have been diagnosed with HeFH through genetic tests or based on symptoms.

Exclusion Criteria

I do not have active liver disease or unexplained high liver enzyme levels.

I am not pregnant or nursing.

Recent and/or planned use of other investigational medicinal products or devices

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Year 1)

Participants receive inclisiran or placebo subcutaneous injections at Days 1, 90, and 270

12 months

3 visits (in-person)

Open-label Treatment (Year 2)

All participants receive inclisiran subcutaneous injections at Days 360, 450, and 630

12 months

3 visits (in-person)

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 tests Inclisiran's safety and effectiveness in lowering bad cholesterol compared to a placebo in kids with HeFH. It's a phase III trial where participants are randomly assigned to receive either Inclisiran or an inactive substance.

How Is the Trial Designed?

Group I: Inclisiran Experimental Treatment 1 Intervention

Year 1 - inclisiran sodium subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium subcutaneous injection (given at Days 450 and 630)

Group II: Placebo Placebo Group 1 Intervention

Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium subcutaneous injection (given at Days 360, 450, and 630)

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

Citations

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

Safety and Efficacy of Inclisiran in Hyperlipidemia Inclisiran reduces LDL‐C, PCSK9, cholesterol and apo‐B levels in the body without increasing the risk of serious adverse events.

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

Long-term efficacy and safety of inclisiran in patients with ... Statin monotherapy results in only 20–40% of very high-risk patients achieving new, lower, recommended LDL cholesterol goals, meaning that those ...

3. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(24)00313-6/fulltext

Inclisiran—Amazing for Cholesterol but Outcome Data ... Both drugs reduced cholesterol by an impressive 50 mg/dL, and both reduced the risk of cardiovascular events by a more modest 15%. The drugs are expensive and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666602222000441

Efficacy and safety of inclisiran a newly approved FDA drug According to our results, inclisiran exerts consistent, favourable effects on several lipid/lipoprotein parameters, including TC, LDL-C, HDL-C, non-HDL-C, apoB ...

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

Inclisiran for the Treatment of Heterozygous Familial ... Among adults with heterozygous familial hypercholesterolemia, those who received inclisiran had significantly lower levels of LDL cholesterol than those who ...

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

Safety and Tolerability of Inclisiran for Treatment ... This analysis indicates that long-term inclisiran is safe and generally well tolerated in a diverse population of patients with dyslipidemia ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1615758

Inclisiran in Patients at High Cardiovascular Risk with ... In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels.