What side effects are associated with this type of intervention?

The most common treatments for hypercholesterolemia include statins, ezetimibe, and PCSK9 inhibitors like Inclisiran. Statins can cause side effects such as muscle pain, liver enzyme abnormalities, and, rarely, rhabdomyolysis. Ezetimibe is generally well-tolerated but can cause gastrointestinal issues and, infrequently, muscle pain. PCSK9 inhibitors, including Inclisiran, are associated with injection site reactions, nasopharyngitis, and flu-like symptoms. Serious adverse events are rare but can include hypersensitivity reactions.

What prior FDA approvals exist?

The FDA has approved several PCSK9 inhibitors for the treatment of hypercholesterolemia, including evolocumab and alirocumab. These drugs are particularly effective in lowering LDL-C levels in patients with familial hypercholesterolemia and are often used in combination with statins and ezetimibe. PCSK9 inhibitors are generally well-tolerated, with common side effects being mild injection site reactions. These treatments have demonstrated significant efficacy in reducing cardiovascular events in high-risk patients.

What other types of research exist?

Promising alternatives to Inclisiran for hypercholesterolemia treatment in 2024 include Evolocumab and Alirocumab, both of which are PCSK9 inhibitors with proven efficacy in reducing LDL cholesterol. Additionally, Bempedoic Acid and Ezetimibe are other non-statin options, though they are generally less effective than PCSK9 inhibitors. Evinacumab, a monoclonal antibody targeting ANGPTL3, is another novel option, particularly for patients with homozygous familial hypercholesterolemia.

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siRNA

Inclisiran for High Cholesterol (ORION-13 Trial)

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation

Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening

Must not have

Documented evidence of a null (negative) mutation in both LDLR alleles

Active liver disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, after day 90 up to day 330

Awards & highlights

Pivotal Trial

Summary

This trial tests inclisiran, a medication that lowers bad cholesterol, in adolescents with a genetic condition causing very high cholesterol. Inclisiran works by blocking a protein that increases cholesterol levels, leading to significant reductions in bad cholesterol.

Who is the study for?

This trial is for adolescents with a genetic condition called homozygous familial hypercholesterolemia (HoFH) and high LDL cholesterol levels, despite being on the highest dose of statins they can tolerate. They should not have used certain other cholesterol drugs recently and must have decent kidney function.

What is being tested?

The study tests Inclisiran, a new medication aimed at lowering LDL cholesterol, against a placebo in young people with severe inherited high cholesterol. It's designed to see if it's safe and effective in reducing their cholesterol levels.

What are the potential side effects?

While specific side effects for Inclisiran are not listed here, common ones may include injection site reactions, allergic responses, liver enzyme changes, muscle pain or weakness, and potential interactions with other lipid-lowering therapies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been genetically diagnosed with Homozygous Familial Hypercholesterolemia.

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My kidney function is above the minimum level required.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My tests show a negative mutation in both LDLR genes.

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I have an ongoing liver condition.

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I have not had a major heart problem in the last month.

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I have a genetic condition that causes high cholesterol.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, after day 90 up to day 330

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, after day 90 up to day 330

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, after day 90 up to day 330 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Low-Density Lipoproteins

Secondary study objectives

% change and absolute change in LDL-C from baseline up to Day 720

% change and absolute change in other lipoprotein and lipid parameters from baseline up to Day 720

% change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720

+1 more

Side effects data

From 2019 Phase 3 trial • 482 Patients • NCT03397121

12%

Nasopharyngitis

Injection site reaction

Upper respiratory tract infection

Back pain

Influenza

Acute myocardial infarction

Aortic valve stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Inclisiran

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: InclisiranExperimental Treatment1 Intervention

Year 1 - inclisiran sodium 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 450 and 630)

Group II: PlaceboPlacebo Group1 Intervention

Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 360, 450, and 630)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inclisiran

2021

Completed Phase 3

~2820

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for hypercholesterolemia include statins, ezetimibe, and PCSK9 inhibitors. Statins work by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis in the liver, leading to reduced LDL-C levels. Ezetimibe reduces cholesterol absorption in the intestines, further lowering LDL-C. PCSK9 inhibitors, such as Inclisiran, work by inhibiting the PCSK9 protein, which increases the number of LDL receptors on liver cells, enhancing the clearance of LDL-C from the bloodstream. These treatments are crucial for hypercholesterolemia patients as they significantly lower LDL-C levels, reducing the risk of cardiovascular events and improving overall heart health.

PCSK9 Inhibitors in Secondary Prevention-An Opportunity for Personalized Therapy.PCSK9 inhibition in LDL cholesterol reduction: genetics and therapeutic implications of very low plasma lipoprotein levels.