Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia (SPRUCE)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Zodasiran

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: SPRUCE@arrowheadpharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zodasiran	Drug: Zodasiran; By sc injection; Other Names: ARO-ANG3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline to Month 12 in Fasting LDL-C	Baseline, Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB)	Baseline, Month 12
Change from Baseline to Month 12 in Fasting ApoB	Baseline, Month 12
Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C)	Baseline, Month 12
Change from Baseline to Month 12 in Fasting Non-HDL-C	Baseline, Month 12
Change from Baseline to Month 12 in Fasting LDL-C	Baseline, Month 12
Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C	Baseline, Month 12
Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs)	Baseline, Month 12
Change from Baseline to Month 12 in Fasting TGs	Baseline, Month 12
Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3)	Baseline, Month 12
Change from Baseline to Month 12 in Fasting ANGPTL3	Baseline, Month 12
Percent Change from Baseline to Month 12 in Fasting Total Cholesterol	Baseline, Month 12
Change from Baseline to Month 12 in Fasting Total Cholesterol	Baseline, Month 12
Percent Change from Baseline to Month 12 in Fasting HDL-C	Baseline, Month 12
Change from Baseline to Month 12 in Fasting HDL-C	Baseline, Month 12
Number of Participants who Meet European Union (EU) LDL-C Apheresis Eligibility Criteria (per German Apheresis Working Group) at Month 12	Month 12
Number of Participants who Meet United States (US) Apheresis Eligibility Criteria (per National Lipid Association) at Month 12	Month 12
Number of Participants with Fasting LDL-C <100 mg/dL at Month 12	Month 12
Percent Change from Baseline in Fasting LDL-C Over Time	Baseline, up to Month 12
Change from Baseline in Fasting LDL-C Over Time	Baseline, up to Month 12
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to 27.5 months

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Genetic Diseases, Inborn; Lipid Metabolism Disorders; Metabolic Diseases; Metabolism, Inborn Errors; Dyslipidemias; Homozygous Familial Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Lipid Metabolism, Inborn Errors; Nutritional and Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemia Type II; Zodasiran
• Additional Relevant MeSH Terms: Homozygous Familial Hypercholesterolemia; Genetic Diseases, Inborn; Dyslipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; zodasiran
• Other Study ID Numbers: AROANG3-3003; 2025-523662-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No