Familial Hypercholesterolemia - HeterozygousPhase 3ORION-20NCT06597019
Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia
A Phase 3 study testing Inclisiran in people with Familial Hypercholesterolemia - Heterozygous, run by Novartis Pharmaceuticals at 66 sites in 23 countries.
Trial summary
This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDLC). Read more about this study
- Who is it for?
- Ages 6 to 11 years
- Conditions the study is for
- Familial Hypercholesterolemia - Heterozygous
- 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
- 60 participants
- Where
- 66 sitesin 23 countries
- Study dates
- 9 Dec 2024to 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 6 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female participants, 6 to <12 years of age at screening
- HeFH diagnosed either by genetic testing or on phenotypic criteria
- Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
- For participants 8 to <12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants <8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
- Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.
Who cannot join
- Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
- Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- Homozygous familial hypercholesterolemia (HoFH)
- Body weight <16 kg at the screening and/or randomization (Day 1) visit
- 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
66 sites in 23 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
66 sites in 23 countries
United States11 sites, 11 recruiting
- Recruiting
Excel Medical Clinical Trials LLC
Boca Raton, Florida, 33434
Mariana Sanchez Villa, +1 561 756 8206, msanchezvilla@flourishresearch.com
Rasha Youssef
- Recruiting
West Virginia Childrens Hospital
Morgantown, West Virginia, 26506
Robin Hoffer, +1 724-972-9170, Robin.Hoffer1@hsc.wvu.edu
Lee Pyles
- Recruiting
West Virginia Childrens Hospital
Morgantown, West Virginia, 26506
Robin Hoffer, +1 878 379 4121, robin.hoffer1@hsc.wvu.edu
Lee Pyles
- Recruiting
Icahn School of Med at Mt Sinai
New York, New York, 10029
Jay Krishna Katragadda, +1 212 659 9174, jaykrishna.katragadda@mssm.edu
Joseph Mahgerefteh
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298
Megan Scott, megan.scott@vcuhealth.org
Bradford McQuilkin
- Not yet recruiting
Primary Childrens Medical Center
Salt Lake City, Utah, 84113
Linda Lambert, Linda.lambert@hsc.utah.edu
Adam Ware
- Recruiting
Primary Childrens Medical Center
Salt Lake City, Utah, 84113
Linda Lambert, +1 801 587 9153, 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
UC San Francisco Medical Center
San Francisco, California, 94143
Luis Gay, +1 415 990 7296, Luis.Gay@ucsf.edu
Martin Thelin
- Not yet recruiting
Children's National Hospital
Washington D.C., District of Columbia, 20010
Carlos Carhuas, +1 202 476 3578, ccarhuas@childrensnational.org
Sarah Clauss
- Recruiting
Childrens National Hospital
Washington D.C., District of Columbia, 20010
Carlos Jesus Carhuas, +1 202 476 5000, ccarhuas@childrensnational.org
Sarah Clauss
Spain8 sites, 8 recruiting
- Recruiting
Novartis Investigative Site
Badalona, Barcelona, 08916
- Recruiting
Novartis Investigative Site
Barcelona, 08041
- Recruiting
Novartis Investigative Site
Cadiz, Andalusia, 11009
- Recruiting
Novartis Investigative Site
Elche, Alicante, 03203
- Recruiting
Novartis Investigative Site
Esplugues, Barcelona, 08950
- Recruiting
Novartis Investigative Site
Málaga, 29011
- Recruiting
Novartis Investigative Site
Pamplona, Navarre, 31008
- Recruiting
Novartis Investigative Site
Seville, 41013
Brazil4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Fortaleza, Ceará, 60430-275
- Recruiting
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90020-020
- Recruiting
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20211-340
- Recruiting
Novartis Investigative Site
São Paulo, São Paulo, 05403 000
Italy4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Milan, MI, 20162
- Recruiting
Novartis Investigative Site
Roma, RM, 00165
- Recruiting
Novartis Investigative Site
Torino, TO, 10126
- Recruiting
Novartis Investigative Site
Verona, VR, 37126
Portugal4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Coimbra, 3000-602
- Recruiting
Novartis Investigative Site
Lisbon, 1649-035
- Recruiting
Novartis Investigative Site
Porto, 4050-651
- Recruiting
Novartis Investigative Site
Porto, 4200 319
France3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Marseille, 13885
- Recruiting
Novartis Investigative Site
Nantes, 44093
- Recruiting
Novartis Investigative Site
Paris, 75012
Germany3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Frankfurt am Main, Hesse, 60590
- Recruiting
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
- Recruiting
Novartis Investigative Site
Hanover, 30173
Poland3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Bialystok, 15-274
- Recruiting
Novartis Investigative Site
Gdansk, 80 952
- Recruiting
Novartis Investigative Site
Lodz, Łódź Voivodeship, 93-338
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
Argentina2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Buenos Aires, C1245AAM
- Recruiting
Novartis Investigative Site
CABA, C1181ACH
Austria2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Salzburg, 5020
- Recruiting
Novartis Investigative Site
Vienna, 1090
Belgium2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Brussels, 1200
- Recruiting
Novartis Investigative Site
Leuven, 3000
China2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Beijing, Beijing Municipality, 100013
- Recruiting
Novartis Investigative Site
Shanghai, 200127
Czechia2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Prague, 128 08
- Recruiting
Novartis Investigative Site
Prague, 150 06
Greece2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Athens, 115 27
- Recruiting
Novartis Investigative Site
Ioannina, 455 00
Israel2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Jerusalem, 9112001
- Recruiting
Novartis Investigative Site
Ramat Gan, 5265601
Taiwan2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Taipei, 111045
- Recruiting
Novartis Investigative Site
Taipei, 11217
United Kingdom2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
London, NW3 2QG
- Recruiting
Novartis Investigative Site
West Midlands, Birmingham, B4 6NH
Hong Kong1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Hong Kong, 999077
Hungary1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Budapest, 1026
Malaysia1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Netherlands1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Amsterdam, North Holland, 1105 AZ
South Africa1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Bloemfontein, Free State, 9301
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 (6 to Less Than 12 Years) With Heterozygous 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 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) 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 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.
- Being tested
- Inclisiran, Placebo
- Keywords
- Heterozygous familial hypercholesterolemia (HeFH),, LDL-cholesterol (LDL-C),, Children,, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Heterozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Heart Failure,, Cardiovascular Diseases,, Cholesterol,, Aortic Stenosis
- Medical subject headings
- Hyperlipoproteinemia Type II, Hypercholesterolemia, Hyperlipidemias, Dyslipidemias, Heart Failure, Cardiovascular Diseases, 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 and inclisiran sodium 180 mg s.c. for participants with body weight <23 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)
Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [percent change] at Day 330
Measured: Baseline and Day 330
Secondary outcomes (13)
Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)
Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [time-adjusted percent change] over Year 1
Measured: Baseline, after Day 90 up to Day 330
Absolute change in LDL-C from baseline to Day 330 (Year 1)
Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [absolute change] at Day 330 (Year 1)
Measured: Baseline and Day 330
Percent change in PCSK9 from baseline to Day 330 (Year 1)
Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C [percent change] at Day 330 (Year 1)
Measured: Baseline and Day 330
Percent change in total cholesterol, non-HDL-C from baseline to Day 330 (Year 1)
Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C [percent change] at Day 330 (Year 1)
Measured: Baseline and Day 330
Percent change in Apo B from baseline to Day 330 (Year 1)
Demonstrate superiority of inclisiran compared to placebo in reducing PCSK9, total cholesterol, Apo B, and non-HDL-C [percent change] at Day 330 (Year 1)
Measured: Baseline and Day 330
Percent change in LDLC, total cholesterol, non-HDLC, 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 LDLC, total cholesterol, non-HDLC, 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 start9 Dec 2024
- 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 - HeterozygousStudies 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
- 60 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
- NCT06597019
- Sponsor's protocol ID
- CKJX839C12303
- Other IDs
- 2024-514594-21
- Acronym
- ORION-20
- Status last verified
- May 2026
- First submitted
- 11 Sep 2024
- Last updated
- 15 May 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.