Clinical trial NCT05217667: Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
Official title: Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Homozygous Familial Hypercholesterolemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 18
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, up to Week 24
Secondary outcomes:
measure: Percent Change from Baseline in Fasting LDL-C (PUC) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Calculated LDL-C Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting Calculated LDL-C Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting ANGPTL3 Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting Total ApoB Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period) 36
measure: Absolute Change from Baseline in Fasting HDL-C Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting Non-HDL-C Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in VLDL-C Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting TC Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Percent Change from Baseline in Fasting Triglycerides (TG) Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Absolute Change from Baseline in Fasting TG Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time
timeFrame: Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
measure: Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24
timeFrame: Week 24
measure: Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Mount Sinai
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: Cincinnati
country: United States
facility: Metabolic and Atherosclerosis Research Center
state: Ohio
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc
state: Quebec
city: Johannesburg
country: South Africa
facility: WCR-Lipids, Carbohydrate Metabolism Unit Area 551, Department of Medicine
Study officials:
References: