An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects with Homozygous Familial Hypercholesterolemia

1. Males and females, * 12 years of age with a diagnosis of homozygous familial hypercholesterolemia 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. ;2. Stable on a low-fat diet ;3. Stable on their pre-existing, lipid-lowering therapies (such as statins, cholesterol-absorption inhibitors, bile-acid sequestrants, or combinations thereof) for at least 4 weeks with no planned medication or dose change for the duration of study participation ;4. Fasting central lab LDL-C concentration >130 mg/dl (3.4 mmol/L) and triglyceride concentration < 400 mg/dL (4.5 mmol/L), ;5. Bodyweight of 40 kg or greater at screening. ;6. Subjects should be willing and able to give written informed consent before initiation of any study-related procedures (if the subject is less than 18 years of age, written consent will be obtained from their guardian or legally authorized representative, with verbal assent from the child).

1. LDL or plasma apheresis within 8 weeks prior to the screening visit, and no plan to receive it during the study because of the attendant difficulty in maintaining stable concentrations of LDL-C while receiving apheresis.;2. Use of Mipomersen or Lomitapide therapy within 5 months of screening.;3. Previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.;4. New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction < 30% or any cardiac arrhythmia within past 3 months that is not controlled by medication.;5. Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of enrollment;6. Planned cardiac surgery or revascularization;7. Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg despite anti-hypertensive therapy.;8. Poorly controlled diabetes mellitus, i.e., glycated hemoglobin A1c (HbA1c) >10.0%.;9. Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2;10. 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 the upper limit of normal (ULN), at screening confirmed by a repeat measurement at least 1 week apart.;11. Creatine kinase (CK) > 5x ULN without a known cause;12. Other serious comorbid disease in which the life expectancy of the subject is shorter than the duration of the trial (e.g., acute systemic infection or other serious illnesses).;13. Any history of malignant disease, with the exception of treated basal-cell carcinoma occurring >5 years before screening.;14. Females who are pregnant or nursing, or who are of childbearing potential (includes adolescent females who have reached menarche and are sexually active) and unwilling to use at least two methods of contraception (e.g., oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion:;a. Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age ;b. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of enrollment ;c. Women who are surgically sterilized at least 3 months prior to enrollment;d. Adolescent females who have not reached menarche;15. Males who are unwilling to use an acceptable method of birth control during the entire study period (e.g., condom with spermicide).;16. Known history of alcohol and/or drug abuse within 5 years.;17. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:;a. Inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator.;b. 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).;c. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).;d. 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.;e. Involved with, or a relative of, someone directly involved in the conduct of the study.;18. Any clinically significant disease or condition affecting a major organ system, including but not limited to gastrointestinal, renal, hepatic, endocrinologic, pulmonary, neurological, metabolic or cardiovascular disease.;19. Any surgical or medical condition which, in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug (if applicable).;20. Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives, whichever is longer, prior to the administration of the study drug, planned use of investigational medicinal products or devices.;21. Previous participation in this study or any preceding study with ALN-PCSSC.;22. Hypersensitivity to any of the ingredients of the study drug being used.