study to evaluate safety, tolerability and efficacy of inclisiran in children with homozygous familial hypercholesterolemia

Conditions: Familial Hypercholesterolemia - Homozygous

Summary: 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).

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

Keywords: homozygous familial hypercholesterolemia (hofh), ldl-cholesterol (ldl-c), children, pediatric, small interfering ribonucleic acid (sirna), inclisiran, familial hypercholesterolemia, homozygous fh, hypercholesterolemia, lipoprotein(a), hyperlipidemia, dyslipidemia, cardiovascular diseases, heart failure, cholesterol, aortic stenosis