Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia
ORION-19
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
2 other identifiers
interventional
9
11 countries
18
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Feb 2025
Typical duration for phase_3
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 11, 2024
CompletedFirst Posted
Study publicly available on registry
September 19, 2024
CompletedStudy Start
First participant enrolled
February 28, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 23, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 15, 2029
February 20, 2026
February 1, 2026
3.1 years
September 11, 2024
February 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage change in LDL-C from baseline to Day 330 (Year 1)
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \[percent change\] at Day 330
Baseline and Day 330
Secondary Outcomes (9)
Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (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)
Baseline, up to Day 720
Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
Baseline, up to Day 720
Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
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)
Baseline, up to Day 720
- +4 more secondary outcomes
Study Arms (2)
Inclisiran
EXPERIMENTALYear 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)
Placebo
PLACEBO COMPARATORYear 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium subcutaneous injection (given at Days 360, 450, and 630)
Interventions
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.
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Eligibility Criteria
You may qualify if:
- Male or female participants, 2 to \<12 years of age at screening
- HoFH diagnosed by genetic confirmation
You may not qualify if:
- 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.
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
UC San Francisco Medical Center
San Francisco, California, 94143, United States
UC San Francisco Medical Center
San Francisco, California, 94143, United States
Childrens National Hospital
Washington D.C., District of Columbia, 20010, United States
Washington Univ School Of Medicine
St Louis, Missouri, 63110, United States
Novartis Investigative Site
Vienna, 1090, Austria
Novartis Investigative Site
Beijing, Beijing Municipality, 100013, China
Novartis Investigative Site
Frankfurt am Main, Hesse, 60590, Germany
Novartis Investigative Site
Ioannina, 455 00, Greece
Novartis Investigative Site
Thessaloniki, 546 42, Greece
Novartis Investigative Site
Kota Bharu, Kelantan, 16150, Malaysia
Novartis Investigative Site
Amsterdam, North Holland, 1105 AZ, Netherlands
Novartis Investigative Site
Bloemfontein, Free State, 9301, South Africa
Novartis Investigative Site
Taichung, 407219, Taiwan
Novartis Investigative Site
Taipei, 111045, Taiwan
Novartis Investigative Site
Adana, Saricam, 01330, Turkey (Türkiye)
Novartis Investigative Site
Ankara, Yenimahalle, 06500, Turkey (Türkiye)
Novartis Investigative Site
Izmir, 35100, Turkey (Türkiye)
Novartis Investigative Site
Southampton, SO16 6YD, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Masked (Year 1) to No Masking (Year 2)
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 11, 2024
First Posted
September 19, 2024
Study Start
February 28, 2025
Primary Completion (Estimated)
March 23, 2028
Study Completion (Estimated)
April 15, 2029
Last Updated
February 20, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
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.