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

Homozygous Familial Hypercholesterolemia Clinical Trial

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Official title:

Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05217667
• Other study ID #: AROANG3-2003
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 22, 2022
• Est. completion date: May 2025

Study information

• Verified date: April 2024
• Source: Arrowhead Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: May 2025
• Est. primary completion date: May 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• ARO-ANG 3 Injection
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

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Linear Clinical Research	Nedlands	Western Australia
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc	Québec	Quebec
South Africa	WCR-Lipids, Carbohydrate Metabolism Unit Area 551, Department of Medicine	Johannesburg
United States	Metabolic and Atherosclerosis Research Center	Cincinnati	Ohio
United States	Icahn School of Medicine at Mt. Sinai	Mount Sinai	New York

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Absolute Change from Baseline in Fasting ANGPTL3 Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	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)
Secondary	Absolute Change from Baseline in Fasting Total ApoB Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	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
Secondary	Absolute Change from Baseline in Fasting HDL-C Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Absolute Change from Baseline in VLDL-C Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	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)
Secondary	Absolute Change from Baseline in Fasting TC Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	Percent Change from Baseline in Fasting Triglycerides (TG) Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	Absolute Change from Baseline in Fasting TG Over Time		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)		Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary	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)
Secondary	Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C = 300 mg/dL at Week 24		Week 24
Secondary	Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24		Week 24