A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

Inclusion Criteria

• Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a history of an untreated LDL-C concentration >500 mg/dL (13 mmol/L) together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents
• Stable on a low-fat diet.
• Subjects on statins should be receiving a maximally tolerated dose. Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable adverse events.
• Subjects not receiving statins must have documented evidence of intolerance to at least two different statins.
• Subjects on lipid-lower therapies (such as statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.
• Fasting central laboratory LDL-C concentration ≥130 mg/dL (3.4 mmol/L).
• Triglyceride concentration 180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy
• 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 >2x upper limit of normal (ULN) at screening confirmed by a repeat measurement at least 1 week apart
• Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than the duration of the trial
• History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or commencement of systemic therapy as treatment during the 3 years prior to randomization
• Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one acceptable effective method of contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion:
• Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age
• Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of enrolment
• Women who are surgically sterilized at least 3 months prior to enrolment
• Known history of alcohol and/or drug abuse within 5 years
• Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
• Subjects who are unable to communicate or to cooperate with the investigator.
• Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
• Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study)
• Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study
• Persons directly involved in the conduct of the study
• Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study
• Any underlying known disease, or surgical, physical, or medical condition that, in the opinion of the Investigator, might interfere with the interpretation of clinical study results
• Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer
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