Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)

NCT05217667 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: AROANG3-2003
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 7

Brief Summary

Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change from Baseline in Fasting Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) and LDL-C by Preparative Ultracentrifugation (LDL-C [PUC]) up to Week 24

  Baseline, up to Week 24

Secondary Outcomes (22)

• Percent Change from Baseline in Fasting LDL-C (PUC) Over Time

  Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)

• Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time

  Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)

• Percent Change from Baseline in Fasting Calculated LDL-C Over Time

  Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)

• Absolute Change from Baseline in Fasting Calculated LDL-C Over Time

  Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)

• Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time

  Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)

Study Arms (2)

ARO-ANG3 Dose 1

EXPERIMENTAL

ARO-ANG3 Dose Level 1 subcutaneous (SC)

Drug: ARO-ANG 3 Injection

ARO-ANG3 Dose 2

EXPERIMENTAL

ARO-ANG3 Dose Level 2 SC

Drug: ARO-ANG 3 Injection

Interventions

ARO-ANG 3 Injection DRUG

Participants will be randomized to receive ARO-ANG3 SC on Day 1 and Day 84 during the initial 36 Weeks of the study and on Day1 and Months 3, 6, 9, 12, 15, 18, and 21 of the extension period

ARO-ANG3 Dose 1; ARO-ANG3 Dose 2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Fasting LDL-C \>100 mg/dL at Screening
• Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2
• Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis
• On stable maximally tolerated lipid lowering therapy
• Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1
• Participants of childbearing potential (males \& females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication.
• Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medications for \> 2 menstrual cycles prior to Day 1
• Willing to provide written informed consent and to comply with study requirements

You may not qualify if:

• Current use or use within 365 days from Day 1 of any hepatocyte targeted small interfering RNA oligonucleotides (siRNA) or antisense oligonucleoside molecule
• Use of evinacumab (some exceptions apply)
• Fasting TG \> 300 mg/dL at Screening
• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
• Newly diagnosed (within 3 months prior to informed consent) or poorly controlled diabetes (Hemoglobin A1c \> 9%)
• Use of systemic corticosteroids (some exceptions apply)
• Symptoms of myocardial ischemia or severe left ventricular dysfunction
• History of metastatic malignancy within 3 years of Day 1 (some exceptions apply)
• Planned cardiac procedure/surgery such as coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), carotid surgery or stenting, or carotid revascularization

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (7)

Research Site 4

Mount Sinai, New York, 10029, United States

Location

Research Site 5

Cincinnati, Ohio, 45227, United States

Location

Research Site 8

Camperdown, New South Wales, 2050, Australia

Location

Research Site 3

Nedlands, Western Australia, 6009, Australia

Location

Research Site 2

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Research Site 1

Québec, Quebec, G1V 4W2, Canada

Location

Research Site 7

Johannesburg, 2193, South Africa

Location

Related Publications (2)

• Raal FJ, Bergeron J, Gaudet D, Rosenson RS, Sullivan DR, Turner T, Hegele RA, Ballantyne CM, Knowles JW, Leeper NJ, Goldberg IJ, Zhou R, Muhsin M, Hellawell J, Hamilton J, Watts GF. Zodasiran, an RNAi therapeutic targeting ANGPTL3, for treating patients with homozygous familial hypercholesterolaemia (GATEWAY): an open-label, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2026 Feb;14(2):123-136. doi: 10.1016/S2213-8587(25)00290-6. Epub 2025 Dec 18.

  PMID: 41422812 DERIVED

• Dimitriadis K, Theofilis P, Iliakis P, Pyrpyris N, Dri E, Sakalidis A, Soulaidopoulos S, Tsioufis P, Fragkoulis C, Chrysohoou C, Tsiachris D, Tsioufis K. Management of dyslipidemia in coronary artery disease: the present and the future. Coron Artery Dis. 2024 Sep 1;35(6):516-524. doi: 10.1097/MCA.0000000000001375. Epub 2024 Apr 29.

  PMID: 38682459 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: February 1, 2022
• Study Start: April 22, 2022
• Primary Completion: May 2, 2023
• Study Completion: November 1, 2025
• Last Updated: October 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); CA (2); ZA (1); US (2)