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

Phase 2

Active, not recruiting

• Conditions: Homozygous Familial Hypercholesterolemia
• Interventions: Drug: ARO-ANG 3 Injection

• Registration Number: NCT05217667
• Lead Sponsor: Arrowhead Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-20
• Study First Submitted QC: 2022-01-20
• Study First Posted: 2022-02-01
• Study Start: 2022-04-22
• Primary Completion: 2023-05-02
• Disposition First Posted: 2023-08-22
• Status Verified: 2024-04
• Disposition First Submitted: 2024-04-30
• Last Update Submitted: 2024-04-30
• Last Update Posted: 2024-05-02
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Note: additional inclusion/exclusion criteria may apply per protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARO-ANG3 Dose 1	ARO-ANG 3 Injection	ARO-ANG3 Dose Level 1 subcutaneous (SC)
ARO-ANG3 Dose 2	ARO-ANG 3 Injection	ARO-ANG3 Dose Level 2 SC

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) 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 Non-HDL-C Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Absolute Change from Baseline in VLDL-C Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24	Week 24
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)
Absolute Change from Baseline in Fasting Total ApoB Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Absolute Change from Baseline in Fasting HDL-C Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Absolute Change from Baseline in Fasting TG Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Absolute Change from Baseline in Fasting ANGPTL3 Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period) 36
Absolute Change from Baseline in Fasting TC Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Percent Change from Baseline in Fasting Triglycerides (TG) Over Time	Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24	Week 24

Trial Locations

Locations (7)

Icahn School of Medicine at Mt. Sinai; 🇺🇸 Mount Sinai, New York, United States

Metabolic and Atherosclerosis Research Center; 🇺🇸 Cincinnati, Ohio, United States

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Clinique des Maladies Lipidiques de Quebec Inc; 🇨🇦 Québec, Quebec, Canada

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

WCR-Lipids, Carbohydrate Metabolism Unit Area 551, Department of Medicine; 🇿🇦 Johannesburg, South Africa