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NCT05127226

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

NCT ID: NCT05127226

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-22

Study Completion Date

2029-03-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Angelman Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1 MAD: Cohort A

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 1 MAD: Cohort B

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 1 MAD: Cohort C

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 1 MAD: Cohort D

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 1 MAD: Cohort E

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.

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 1 MAD: Cohort F

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 2 Group 1

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 2 Group 2

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 3 Group 1

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Part 3 Group 2

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

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Interventions

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ION582

ION582 will be administered by IT injection.

Intervention Type DRUG

Eligibility Criteria

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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.

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.

Minimum Eligible Age

0 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Rady Children's Hospital

San Diego, California, United States

Site Status RECRUITING

Colorado Children's Hospital Research Institute

Aurora, Colorado, United States

Site Status RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill School of Medicine

Carrboro, North Carolina, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

Sydney Children's Hospital, Kids Cancer Centre

Randwick, , Australia

Site Status ACTIVE_NOT_RECRUITING

Necker-Enfants Malades Hospital

Paris, , France

Site Status RECRUITING

Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Azienda Ospedaliera Universitaria Pisana

Pisa, , Italy

Site Status RECRUITING

STRONG Group University of Oxford

Oxford, Oxfordshire, United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Australia France Israel Italy United Kingdom

Central Contacts

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Ionis Pharmaceuticals

Role: CONTACT

Phone: (844) 200-6263

Email: [email protected]

Other Identifiers

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2021-003009-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ION582-CS1

Identifier Type: -

Identifier Source: org_study_id