Familial Hypercholesterolemia - HomozygousPhase 3ORION-19NCT06597006
Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia
A Phase 3 study testing Inclisiran in people with Familial Hypercholesterolemia - Homozygous, run by Novartis Pharmaceuticals at 19 sites in 11 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- Familial Hypercholesterolemia - Homozygous
- What is being tested?
- Inclisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 19 sitesin 11 countries
- Study dates
- 28 Feb 2025to 15 Apr 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
19 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
19 sites in 11 countries
United States4 sites, 4 recruiting
- Recruiting
Primary Childrens Medical Center
Salt Lake City, Utah, 84113
Linda Lambert, Linda.lambert@hsc.utah.edu
Adam Ware
- Recruiting
UC San Francisco Medical Center
San Francisco, California, 94143-0348
Luis Gay, +1 415 476 8338, luis.gay@ucsf.edu
Martin Thelin
- Recruiting
Washington Univ School Of Medicine
St Louis, Missouri, 63110
Jodi Pagano, jpagano@wustl.edu
Anne Goldberg
- Recruiting
Childrens National Hospital
Washington D.C., District of Columbia, 20010
Desiree Tobechukwu Nwanze, +1 202 476 5000, dnwanze@childrensnational.org
Sarah Clauss
Turkey (Türkiye)3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Adana, Saricam, 01330
- Recruiting
Novartis Investigative Site
Ankara, Yenimahalle, 06500
- Recruiting
Novartis Investigative Site
Izmir, 35100
Greece2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Ioannina, 455 00
- Recruiting
Novartis Investigative Site
Thessaloniki, 546 42
South Africa2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Bloemfontein, Free State, 9301
- Recruiting
Novartis Investigative Site
Johannesburg, Gauteng, 2193
Taiwan2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Taichung, 407219
- Recruiting
Novartis Investigative Site
Taipei, 111045
Austria1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Vienna, 1090
China1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Beijing, Beijing Municipality, 100013
Germany1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Frankfurt am Main, Hesse, 60590
Malaysia1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Kota Bharu, Kelantan, 16150
Netherlands1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Amsterdam, North Holland, 1105 AZ
United Kingdom1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Southampton, SO16 6YD
About this study
Official title: 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).
Read the 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.
- Being tested
- Inclisiran, Placebo
- Keywords
- Homozygous familial hypercholesterolemia (HoFH),, LDL-cholesterol (LDL-C), children, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Homozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Cardiovascular Diseases,, Heart Failure,, Cholesterol,, Aortic Stenosis
- Medical subject headings
- Homozygous Familial Hypercholesterolemia, Hyperlipoproteinemia Type II, Hypercholesterolemia, Hyperlipidemias, Dyslipidemias, Cardiovascular Diseases, Heart Failure, Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InclisiranDrug
Also called KJX839
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.
PlaceboDrug
Also called saline solution
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
| Study group | Role | What they receive |
|---|---|---|
| Inclisiran | Experimental | 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) Receives: Drug: Inclisiran |
| Placebo | Placebo comparator | 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1
Measured: 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)
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
Measured: Baseline, up to Day 720
Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: Baseline, up to Day 720
Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: 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)
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
Measured: Baseline, up to Day 720
Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: Baseline, up to Day 720
Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: Baseline, up to Day 720
Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: Baseline, up to Day 720
Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)
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
Measured: Baseline, up to Day 720
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start28 Feb 2025
- Primary completion21 Mar 2028 (estimated)
- Study completion15 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Hypercholesterolemia - HomozygousStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel (Year 1) to single-group (Year 2)
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06597006
- Sponsor's protocol ID
- CKJX839C12304
- Other IDs
- 2024-514595-41
- Acronym
- ORION-19
- Status last verified
- Jul 2026
- First submitted
- 11 Sep 2024
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.