Inclisiran for High Cholesterol

(ORION-13 Trial)

Recruiting at 17 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Statins

Must not be taking: PCSK9 antibodies, Mipomersen, Lomitapide

Disqualifiers: Active liver disease, Secondary hypercholesterolemia, 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: 6

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on a stable dose of statins or other lipid-lowering therapy for at least 30 days before joining. If you are taking certain medications like mipomersen or lomitapide, you need to stop them 5 months before screening.

How is the drug Inclisiran different from other treatments for high cholesterol?

Inclisiran is unique because it uses a small interfering RNA (siRNA) mechanism to lower cholesterol by targeting the PCSK9 protein, which is different from traditional statins that inhibit cholesterol production in the liver. It is administered as an injection every six months, offering a less frequent dosing schedule compared to daily oral medications. ^{1 2 3 4 5}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have been genetically diagnosed with Homozygous Familial Hypercholesterolemia.

Your cholesterol level is too high when you haven't eaten for a while.

I have been on the highest dose of statin I can tolerate for at least 30 days.

Exclusion Criteria

My tests show a negative mutation in both LDLR genes.

I have not taken mipomersen or lomitapide in the last 5 months.

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 either 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
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Part 2 - Inclisiran (Total) Experimental Treatment 1 Intervention

Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.

Group II: Part 1 - Inclisiran Experimental Treatment 1 Intervention

Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

Group III: Part 1 - Placebo Placebo Group 1 Intervention

Placebo sc injection (given at Day 1, 90 and 270)

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 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]

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]

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 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]

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]

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology. [2022]

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

Small Molecules for Psoriasis. [2019]

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

Small Molecules for Psoriasis. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Open-label exploratory study of acitretin for the treatment of severe chronic hand dermatitis. [2018]

5. Sweden pubmed.ncbi.nlm.nih.gov

Effects of gemfibrozil (Lopid) on hyperlipidemia in acitretin-treated patients. Results of a double-blind cross-over study. [2019]