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

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 allelesare 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 beon a stable dose for ≥30 days before screening with no planned medication or dosechanges during study participation

• Participants on a documented regimen of LDL-apheresis for ≥ 3 months beforescreening will be allowed to continue the apheresis during the study, if needed. Theapheresis schedule/settings/duration must be stable prior to screening, are notallowed to change during the double-blind period of the trial and must permit thatan 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 directedtowards PCSK9

• History of poor response to therapy with any monoclonal antibody directed towardsPCSK9 (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 forparticipants 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, ormetabolic pathology of the liver or unexplained alanine aminotransferase (ALT),aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2xULN (except patients with Gilbert's syndrome)

• Pregnant or nursing females

• Recent and/or planned use of other investigational medicinal products or devices