Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia

Official title

Phase 3 Single-Arm Open-Label Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent Participants (Age 12 to <18 Years) With Homozygous Familial Hypercholesterolemia (SPRUCE)

Overview

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.

Interventions

• Drug Zodasiran
  By sc injection

Primary outcome measures

• Percent Change from Baseline to Month 12 in Fasting LDL-C [Time frame: Baseline, Month 12]

Secondary outcome measures (12)

• Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting ApoB [Time frame: Baseline, Month 12]
• Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting Non-HDL-C [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting LDL-C [Time frame: Baseline, Month 12]
• Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C [Time frame: Baseline, Month 12]
• Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting TGs [Time frame: Baseline, Month 12]
• Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting ANGPTL3 [Time frame: Baseline, Month 12]
• Percent Change from Baseline to Month 12 in Fasting Total Cholesterol [Time frame: Baseline, Month 12]
• Change from Baseline to Month 12 in Fasting Total Cholesterol [Time frame: Baseline, Month 12]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07473843 · AROANG3-3003 · 2025-523662-24-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗