Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia (ORION-19)

February 18, 2026 updated by: Novartis Pharmaceuticals

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Children (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Novartis Investigative Site
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100013
        • Recruiting
        • Novartis Investigative Site
  • Germany
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60590
        • Recruiting
        • Novartis Investigative Site
  • Greece
      • Ioannina, Greece, 455 00
        • Recruiting
        • Novartis Investigative Site
      • Thessaloniki, Greece, 546 42
        • Recruiting
        • Novartis Investigative Site
  • Malaysia
    • Kelantan
      • Kota Bharu, Kelantan, Malaysia, 16150
        • Recruiting
        • Novartis Investigative Site
  • Netherlands
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1105 AZ
        • Recruiting
        • Novartis Investigative Site
  • South Africa
    • Free State
      • Bloemfontein, Free State, South Africa, 9301
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Taichung, Taiwan, 407219
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 111045
        • Recruiting
        • Novartis Investigative Site
  • Turkey (Türkiye)
      • Izmir, Turkey (Türkiye), 35100
        • Recruiting
        • Novartis Investigative Site
    • Saricam
      • Adana, Saricam, Turkey (Türkiye), 01330
        • Recruiting
        • Novartis Investigative Site
    • Yenimahalle
      • Ankara, Yenimahalle, Turkey (Türkiye), 06500
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • Novartis Investigative Site
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • UC San Francisco Medical Center
        • Principal Investigator:
          • Martin Thelin
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • Childrens National Hospital
        • Principal Investigator:
          • Sarah Clauss
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington Univ School Of Medicine
        • Principal Investigator:
          • Anne Goldberg
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female participants, 2 to <12 years of age at screening

  • HoFH diagnosed by genetic confirmation

    - Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also exclusion criteria)

  • Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
  • On an optimal dose of statin (investigator's discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)
  • Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation
  • Participants on a documented regimen of LDL-apheresis for ≥ 3 months before screening will be allowed to continue the apheresis during the study, if needed. The apheresis schedule/settings/duration must be stable prior to screening, are not allowed to change during the double-blind period of the trial and must permit that an apheresis coincides with each study visit.

Exclusion Criteria:

  • Documented evidence of a null (negative) mutation in both LDLR alleles
  • Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
  • History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
  • Treatment with mipomersen or lomitapide (within 5 months of screening)
  • Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
  • Heterozygous familial hypercholesterolemia (HeFH)
  • Body weight (at the screening and/or randomization (Day 1) visit) <16 kg for participants 6 to <12 years (at screening) or <11 kg for participants 2 to <6 years (at screening)
  • Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome)
  • Pregnant or nursing females
  • Recent and/or planned use of other investigational medicinal products or devices

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Inclisiran
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)
Drug: Inclisiran
Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg, inclisiran sodium 180 mg s.c. for participants with body weight <23 kg to ≥16 kg, or inclisiran sodium 100 mg s.c. for participants with body weight <16 kg. The dose level is based on the participant's body weight on Day 1 (for Part 1) and Day 360 (for Part 2), respectively.
Other Names:
  • KJX839
Placebo Comparator: Placebo
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)
Drug: Placebo
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Other Names:
  • saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage change in LDL-C from baseline to Day 330 (Year 1)
Time Frame: Baseline and Day 330
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [percent change] at Day 330
Baseline and Day 330

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)
Time Frame: Baseline, after Day 90 up to Day 330
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1
Baseline, after Day 90 up to Day 330
Percent change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720
Absolute change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)
Time Frame: Baseline, up to Day 720
Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
Baseline, up to Day 720

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2025

Primary Completion (Estimated)

March 23, 2028

Study Completion (Estimated)

April 15, 2029

Study Registration Dates

First Submitted

September 11, 2024

First Submitted That Met QC Criteria

September 11, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

February 20, 2026

Last Update Submitted That Met QC Criteria

February 18, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CKJX839C12304
  • 2024-514595-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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