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Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia
NCT06597006 · Novartis
In plain English
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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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 9 participants
Allocation: randomized
Masking: double
Age groups: child
Timeline
Starts: 2025-02-28
Estimated completion: 2029-04-15
Last updated: 2026-02-20
Interventions
Drug: InclisiranDrug: Placebo
Primary outcomes
- • Percentage change in LDL-C from baseline to Day 330 (Year 1) (Baseline and Day 330)
Sponsor
Novartis Pharmaceuticals · industry
Contacts & investigators
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · 1-888-669-6682
ContactNovartis Pharmaceuticals · contact · +41613241111
InvestigatorNovartis Pharmaceuticals · study_director, Novartis Pharmaceuticals
All locations (18)
UC San Francisco Medical CenterRecruiting
San Francisco, California, United States
UC San Francisco Medical CenterRecruiting
San Francisco, California, United States
Childrens National HospitalRecruiting
Washington D.C., District of Columbia, United States
Washington Univ School Of MedicineRecruiting
St Louis, Missouri, United States
Novartis Investigative SiteRecruiting
Vienna, Austria
Novartis Investigative SiteRecruiting
Beijing, Beijing Municipality, China
Novartis Investigative SiteRecruiting
Frankfurt am Main, Hesse, Germany
Novartis Investigative SiteRecruiting
Ioannina, Greece
Novartis Investigative SiteRecruiting
Thessaloniki, Greece
Novartis Investigative SiteRecruiting
Kota Bharu, Kelantan, Malaysia
Novartis Investigative SiteRecruiting
Amsterdam, North Holland, Netherlands
Novartis Investigative SiteRecruiting
Bloemfontein, Free State, South Africa
Novartis Investigative SiteRecruiting
Taichung, Taiwan
Novartis Investigative SiteRecruiting
Taipei, Taiwan
Novartis Investigative SiteRecruiting
Adana, Saricam, Turkey (Türkiye)
Novartis Investigative SiteRecruiting
Ankara, Yenimahalle, Turkey (Türkiye)
Novartis Investigative SiteRecruiting
Izmir, Turkey (Türkiye)
Novartis Investigative SiteRecruiting
Southampton, United Kingdom