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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05217667




Registration number
NCT05217667
Ethics application status
Date submitted
20/01/2022
Date registered
1/02/2022
Date last updated
2/05/2024

Titles & IDs
Public title
Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
Scientific title
Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)
Secondary ID [1] 0 0
AROANG3-2003
Universal Trial Number (UTN)
Trial acronym
Gateway
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Homozygous Familial Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-ANG 3 Injection

Experimental: ARO-ANG3 Dose 1 - ARO-ANG3 Dose Level 1 subcutaneous (SC)

Experimental: ARO-ANG3 Dose 2 - ARO-ANG3 Dose Level 2 SC


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, up to Week 24
Secondary outcome [1] 0 0
Percent Change from Baseline in Fasting LDL-C (PUC) Over Time
Timepoint [1] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [2] 0 0
Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time
Timepoint [2] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [3] 0 0
Percent Change from Baseline in Fasting Calculated LDL-C Over Time
Timepoint [3] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [4] 0 0
Absolute Change from Baseline in Fasting Calculated LDL-C Over Time
Timepoint [4] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [5] 0 0
Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time
Timepoint [5] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [6] 0 0
Absolute Change from Baseline in Fasting ANGPTL3 Over Time
Timepoint [6] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [7] 0 0
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time
Timepoint [7] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [8] 0 0
Absolute Change from Baseline in Fasting Total ApoB Over Time
Timepoint [8] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [9] 0 0
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time
Timepoint [9] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period) 36
Secondary outcome [10] 0 0
Absolute Change from Baseline in Fasting HDL-C Over Time
Timepoint [10] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [11] 0 0
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time
Timepoint [11] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [12] 0 0
Absolute Change from Baseline in Fasting Non-HDL-C Over Time
Timepoint [12] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [13] 0 0
Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time
Timepoint [13] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [14] 0 0
Absolute Change from Baseline in VLDL-C Over Time
Timepoint [14] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [15] 0 0
Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time
Timepoint [15] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [16] 0 0
Absolute Change from Baseline in Fasting TC Over Time
Timepoint [16] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [17] 0 0
Percent Change from Baseline in Fasting Triglycerides (TG) Over Time
Timepoint [17] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [18] 0 0
Absolute Change from Baseline in Fasting TG Over Time
Timepoint [18] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [19] 0 0
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Timepoint [19] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [20] 0 0
Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time
Timepoint [20] 0 0
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Secondary outcome [21] 0 0
Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C = 300 mg/dL at Week 24
Timepoint [21] 0 0
Week 24
Secondary outcome [22] 0 0
Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24
Timepoint [22] 0 0
Week 24

Eligibility
Key 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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
South Africa
State/province [4] 0 0
Johannesburg

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05217667
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05217667