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RECRUITINGPhase 3INTERVENTIONAL

Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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).

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Should NOT Join This Trial: - 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) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

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.

DRUG

Placebo

Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)

Locations (18)

UC San Francisco Medical Center
San Francisco, California, United States
UC San Francisco Medical Center
San Francisco, California, United States
Childrens National Hospital
Washington D.C., District of Columbia, United States
Washington Univ School Of Medicine
St Louis, Missouri, United States
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Beijing, Beijing Municipality, China
Novartis Investigative Site
Frankfurt am Main, Hesse, Germany
Novartis Investigative Site
Ioannina, Greece
Novartis Investigative Site
Thessaloniki, Greece
Novartis Investigative Site
Kota Bharu, Kelantan, Malaysia
Novartis Investigative Site
Amsterdam, North Holland, Netherlands
Novartis Investigative Site
Bloemfontein, Free State, South Africa
Novartis Investigative Site
Taichung, Taiwan
Novartis Investigative Site
Taipei, Taiwan
Novartis Investigative Site
Adana, Saricam, Turkey (Türkiye)
Novartis Investigative Site
Ankara, Yenimahalle, Turkey (Türkiye)
Novartis Investigative Site
Izmir, Turkey (Türkiye)
Novartis Investigative Site
Southampton, United Kingdom