HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome

Ionis Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Angelman Syndrome

Treatments: Drug: ION582

Study type: Interventional

Funder types: Industry

Identifiers

NCT05127226

ION582-CS1

2021-003009-23 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of ascending doses of ION582 administered intrathecally in participants with Angelman syndrome.

Full description

This is a Phase 1-2a, open-label study consisting of 3 parts in approximately 70 participants. Part 1 is a multiple ascending dose (MAD) study, consisting of a 13-week MAD Treatment Period and a minimum 12-week Post-MAD Follow-Up Period. Part 2 is a multi-center 49-week study where participants who completed Part 1 will receive IT bolus doses of ION582 followed by a minimum 12-week Part 2 follow up period. Part 3 extends the treatment period for participants who completed Part 2 for up to an additional 3 years followed by a 32-week post-LTE follow up period.

The study was amended in late 2025 to include a cohort of people with Angelman Syndrome under the age of 2 years old. Recruitment sites listed as "Recruiting" below are eligible to recruit individuals into this new cohort only. This page will continue to be updated to reflect the recruitment status of sites and the study. For more information, speak with your doctor or see the Study Contact information below.

Enrollment: 70 estimated patients

Sex: All

Ages: Under 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Participant has a documented and certified diagnosis of Angelman syndrome (AS) (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)
2. Male or female between the ages of 0-50 years of age, with signed informed consent from parent(s) or legal guardian(s)
3. Currently receiving stable standard of care treatments such as, stable doses of anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and including special diets, supplements or nutritional support for at least 3 months prior to first dose.
4. Follow good study practice and not participate in the sharing of personal or study information on social media platforms, such as any website or social media site (e.g., Facebook, Instagram, Twitter, YouTube, etc.) until notified that the study is completed.

Key Exclusion Criteria:

1. Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or imprinting defect (ID).
2. Any clinically significant (CS) cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, will make the patient unsuitable for participation in, and/or unable to complete the study procedures. Has poorly controlled seizures as determined by the Investigator or has documented Status Epilepticus in the past 6 months that could pose a safety risk while on study.
3. Known bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid, antisense oligonucleotide [ASOs]). COVID-19 vaccinations are allowed.
4. Any prior use of gene therapy. Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion or could interfere with the participant taking part in or completing the study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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70 participants in 10 patient groups

Part 1 MAD: Cohort A

Experimental group

Description:

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Treatment:

Drug: ION582

Part 1 MAD: Cohort B

Experimental group

Description:

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Treatment:

Drug: ION582

Part 1 MAD: Cohort C

Experimental group

Description:

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Treatment:

Drug: ION582

Part 1 MAD: Cohort D

Experimental group

Description:

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Treatment:

Drug: ION582

Part 1 MAD: Cohort E

Experimental group

Description:

ION582 will be administered as IT injection of over a period of 13 weeks, with a minimum of approximately 4 weeks between each dose administration.

Treatment:

Drug: ION582

Part 1 MAD: Cohort F

Experimental group

Description:

ION582 will be administered as IT injection over a period of 13 weeks, with a minimum of approximately 12 weeks between each dose administration.

Treatment:

Drug: ION582

Part 2 Group 1

Experimental group

Description:

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Treatment:

Drug: ION582

Part 2 Group 2

Experimental group

Description:

ION582 will be administered as IT injection of over a period of 49 weeks, with additional dosing intervals.

Treatment:

Drug: ION582

Part 3 Group 1

Experimental group

Description:

ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.

Treatment:

Drug: ION582

Part 3 Group 2

Experimental group

Description:

ION582 will be administered as IT injection of over a period of 145 weeks, with additional dosing intervals.

Treatment:

Drug: ION582