Study to evaluate efficacy and safety of inclisiran in children aged 2 to under 12 years of age with homozygous familial hypercholesterolemia

Prior treatment

• Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
• Treatment with mipomersen or lomitapide (within 5 months of screening)

Other illness

• History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome

Lab values

• 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)

Age

• 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)

Other

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Recent and/or planned use of other investigational medicinal products or devices
• Heterozygous familial hypercholesterolemia (HeFH)
• Pregnant or nursing females

• 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
• 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 (≥90 days for evinacumab) 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.