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Homozygous Familial HypercholesterolemiaPhase 2GatewayNCT05217667

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

A Phase 2 study testing ARO-ANG 3 Injection in people with Homozygous Familial Hypercholesterolemia, run by Arrowhead Pharmaceuticals at 7 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Homozygous Familial Hypercholesterolemia
What is being tested?
ARO-ANG 3 Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
7 sitesin 4 countries
Study dates
22 Apr 2022to 13 Nov 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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

Who cannot join

  • 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)
Show all 10Show fewer
  • 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 locations and contacts

7 sites in 4 countries.

7 sites in 4 countries

United States2 sites

  • Research Site 5

    Cincinnati, Ohio, 45227

  • Research Site 4

    Mount Sinai, New York, 10029

Other trials in United States

Australia2 sites

  • Research Site 8

    Camperdown, New South Wales, 2050

  • Research Site 3

    Nedlands, Western Australia, 6009

Other trials in Australia

Canada2 sites

  • Research Site 2

    Chicoutimi, Quebec, G7H 7K9

  • Research Site 1

    Québec, Quebec, G1V 4W2

Other trials in Canada

South Africa1 site

  • Research Site 7

    Johannesburg, 2193

Other trials in South Africa

About this study

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

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.

Being tested
ARO-ANG 3 Injection
Medical subject headings
Homozygous Familial Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARO-ANG 3 InjectionDrug

    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

Study groups in NCT05217667
Study groupRoleWhat they receive
ARO-ANG3 Dose 1ExperimentalARO-ANG3 Dose Level 1 subcutaneous (SC)
Receives: Drug: ARO-ANG 3 Injection
ARO-ANG3 Dose 2ExperimentalARO-ANG3 Dose Level 2 SC
Receives: Drug: ARO-ANG 3 Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Fasting LDL-C at Week 24

    LDL-C, computed using Friedewald formula, Martin-Hopkins methodology and preparative ultracentrifugation (PUC).

    Measured: Baseline, Week 24

Secondary outcomes (24)

  1. Percent Change From Baseline in Fasting LDL-C (PUC) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  2. Absolute Change From Baseline in Fasting LDL-C (PUC) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  3. Percent Change From Baseline in Fasting Calculated LDL-C (Friedewald Formula) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  4. Absolute Change From Baseline in Fasting Calculated LDL-C (Friedewald Formula) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  5. Percent Change From Baseline in Fasting Calculated LDL-C (Martin-Hopkins Methodology) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  6. Absolute Change From Baseline in Fasting Calculated LDL-C (Martin-Hopkins Methodology) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  7. Percent Change From Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  8. Absolute Change From Baseline in Fasting ANGPTL3 Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  9. Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  10. Absolute Change From Baseline in Fasting Total ApoB Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  11. Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  12. Absolute Change From Baseline in Fasting HDL-C Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  13. Percent Change From Baseline in Fasting Non-HDL-C Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  14. Absolute Change From Baseline in Fasting Non-HDL-C Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  15. Percent Change From Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  16. Absolute Change From Baseline in Fasting VLDL-C Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  17. Percent Change From Baseline in Fasting Total Cholesterol (TC) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  18. Absolute Change From Baseline in Fasting TC Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  19. Percent Change From Baseline in Fasting Triglycerides (TG) Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  20. Absolute Change From Baseline in Fasting TG Over Time

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 (Day 1 of Extension Period), Extension Months 1, 2, 3, 6, 9, 12, 15, 18, 21

  21. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE occurring during any study phase that: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medically important event or reaction that may require medical intervention to prevent one of the outcomes listed above. AEs are considered treatment-related if the relationship to the study drug is 'possibly related', 'probably related'. A TEAE is defined as an AE that occurs following IP administration or a pre-existing condition exacerbated following IP administration. Injection site reactions are assessed at every visit starting on Day 1 and include any Preferred Term containing 'Injection Site'.

    Measured: From first dose of study drug up to Week 36 (initial treatment period), and up to Month 24 (extension period)

  22. Number of Participants With Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time

    Measured: Baseline, Day 1, Weeks 4, 12, 16, 24 (initial treatment period), Week 36/Day 1, Months 1, 3, 6, 9, 12, 15, 18, 21 (extension period)

  23. Percentage of Participants Meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24

    Apheresis is the extracorporeal process of removing one or more blood constituents from whole blood and returning the remainder to the circulation.The National Lipid Association outlines eligibility criteria for apheresis, particularly for patients with familial hypercholesterolemia who have not achieved target LDL cholesterol levels despite maximally tolerated pharmacotherapy. LDL-C ≥ 300 mg/dL is a criterion.

    Measured: Week 24

  24. Percentage of Participants Meeting European Union (EU) Apheresis Eligibility Criteria Per German Apheresis Working Group at Week 24

    Apheresis is the extracorporeal process of removing one or more blood constituents from whole blood and returning the remainder to the circulation. The European Union (EU) apheresis eligibility criteria (per German Apheresis Working Group) include the following categories:

    • A patient with primary cardiovascular disease (CVD) prevention is considered as meeting German apheresis eligibility criteria if LDL-C >160 mg/dL
    • A patient with secondary CVD prevention is considered as meeting German apheresis eligibility criteria if LDL-C >120 mg/dL

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2022
  2. Study start22 Apr 2022
  3. Primary completion2 May 2023
  4. Study completion13 Nov 2025

Why it stopped: Business decision, unrelated to safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05217667
Sponsor's protocol ID
AROANG3-2003
Acronym
Gateway
Status last verified
May 2026
First submitted
20 Jan 2022
Last updated
12 Jun 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Raal FJ, Bergeron J, Gaudet D, Rosenson RS, Sullivan DR, Turner T, Hegele RA, Ballantyne CM, Knowles JW, Leeper NJ, Goldberg IJ, Zhou R, Muhsin M, Hellawell J, Hamilton J, Watts GF. Zodasiran, an RNAi therapeutic targeting ANGPTL3, for treating patients with homozygous familial hypercholesterolaemia (GATEWAY): an open-label, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2026 Feb;14(2):123-136. doi: 10.1016/S2213-8587(25)00290-6. Epub 2025 Dec 18.

    PubMed 41422812

  • Dimitriadis K, Theofilis P, Iliakis P, Pyrpyris N, Dri E, Sakalidis A, Soulaidopoulos S, Tsioufis P, Fragkoulis C, Chrysohoou C, Tsiachris D, Tsioufis K. Management of dyslipidemia in coronary artery disease: the present and the future. Coron Artery Dis. 2024 Sep 1;35(6):516-524. doi: 10.1097/MCA.0000000000001375. Epub 2024 Apr 29.

    PubMed 38682459

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ARO-ANG 3 Injection in people with Homozygous Familial Hypercholesterolemia, run by Arrowhead Pharmaceuticals at 7 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Australia, Canada, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Fasting LDL-C at Week 24 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05217667, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.

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