This study will evaluate the efficacy and safety of zodasiran subcutaneous (sc) injection in participants 12 to <18 years of age with genetically or clinically diagnosed homozygous familial hypercholesterolemia (HoFH) and low-density lipoprotein cholesterol (LDL-C) ≥116 milligrams per deciliter (mg/dL) on maximally tolerated lipid-lowering therapy.

Inclusion Criteria:

• Adolescents 12 to <18 years of age who are nonpregnant, nonlactating, and do not plan to become pregnant during the study
• Body weight ≥35 kilograms (kg) at screening
• HoFH based on a supportive genetic test (from a source-verifiable medical record or based on screening genotype) or clinical diagnosis
• Screening LDL-C ≥116 mg/dL (3 mmol/L)
• Screening hemoglobin A1c (HbA1c) ≤9.5%
• Total bilirubin <2×upper limit of normal (ULN), unless in previously confirmed cases of Gilbert's syndrome
• Alanine aminotransferase or aspartate aminotransferase <3×ULN

Exclusion Criteria:

• Use of a hepatocyte-targeted siRNA within 365 days before Day 1 (except inclisiran, which is permitted; administration of inclisiran and study drug must be separated by at least 4 weeks)
• Use of an antisense oligonucleotide molecule within 3 months before Day 1
• Use of evinacumab within 3 months before Day 1
• Non-response to evinacumab, defined as LDL-C reduction <15% from baseline after 2 doses
• Use of systemic corticosteroids (unless used as replacement therapy for pituitary/adrenal disease with a stable regimen)

NOTE: Additional inclusion/exclusion criteria may apply per protocol