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

Arrowhead Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2

Conditions: Homozygous Familial Hypercholesterolemia

Treatments: Drug: ARO-ANG 3 Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05217667

AROANG3-2003

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 2 patient groups

ARO-ANG3 Dose 1

Experimental group

Description:

ARO-ANG3 Dose Level 1 subcutaneous (SC)

Treatment:

Drug: ARO-ANG 3 Injection

ARO-ANG3 Dose 2

Experimental group

Description:

ARO-ANG3 Dose Level 2 SC

Treatment:

Drug: ARO-ANG 3 Injection