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REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome

NCT ID: NCT06914609

Last Updated: 2025-11-06

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

PHASE3

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-10

Study Completion Date

2030-04-30

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of ION582 in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene.

Detailed Description

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This is a Phase 3, randomized, double-blind, placebo-controlled study in people with Angelman syndrome. The study will consist of 4 periods: a screening period of up to 28 days, an approximate 60-week double blind, placebo-controlled treatment period, followed by an approximate 25-month Long-Term Extension (LTE) treatment period, and an approximate 8-month Post-LTE follow-up period. The study will be comprised of 2 cohorts. Cohort 1 will include pediatric participants, aged 2 to less than (\<)18 years old and serve as the population for evaluation of primary and secondary outcome measures; Cohort 2 will include adult participants, aged 18 to ≤50 years old. Participants will be randomized 1:1:1 to 40 mg ION582, 80 mg ION582 or placebo during the double-blind placebo-controlled treatment period. Participants from both cohorts completing the placebo-controlled treatment period will be eligible to transition into the LTE Treatment Period wherein all trial participants will receive ION582. Participant, Caregiver, Investigator and Sponsor will remain blinded to the ION582 dose administered to participants during the LTE.

Conditions

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Angelman Syndrome

Keywords

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ION582 Angelman Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort 1 ION582 40 milligrams (mg)

Participants (aged 2 to \<18 years old) will be administered ION582 40 mg via intrathecal (IT) injection every 12 weeks (Q12W) during the double blind and LTE treatment periods.

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Cohort 1 ION582 80 mg

Participants (aged 2 to \<18 years old) will be administered ION582 80 mg via IT injection Q12W during the double blind and LTE treatment periods.

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Cohort 1 Placebo

Participants (aged 2 to \<18 years old) will be administered ION582 matching placebo via IT injection Q12W during the double-blind treatment period and then administered ION582 40 mg or 80 mg Q12W during the LTE treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

ION582 matching placebo will be administered by IT injection.

Cohort 2 ION582 40 mg

Participants (aged 18 to ≤50 years old) will be administered ION582 40 mg via IT injection Q12W during the double blind and LTE treatment periods.

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Cohort 2 ION582 80 mg

Participants (aged 18 to ≤50 years old) will be administered ION582 80 mg via IT injection Q12W during the double blind and LTE treatment periods.

Group Type EXPERIMENTAL

ION582

Intervention Type DRUG

ION582 will be administered by IT injection.

Cohort 2 Placebo

Participants (aged 18 to ≤50 years old) will be administered ION582 matching placebo via IT injection Q12W during the double-blind treatment period and then randomized to ION582 40 mg or 80 mg Q12W during the LTE treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

ION582 matching placebo will be administered by IT injection.

Interventions

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ION582

ION582 will be administered by IT injection.

Intervention Type DRUG

Placebo

ION582 matching placebo will be administered by IT injection.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. The participants caregiver(s)/ legally authorized representative must have given written informed consent and any authorizations required by local law and be able to comply with all study requirements.
2. Medically stable and can undergo sedation and/or general anesthesia without intubation.
3. Male or female between 2 and lesser than or equal to (≤)50 years of age, depending on specific cohort, at the time of the in-clinic Screening visit.
4. Participant has a documented diagnosis of Angelman syndrome (AS) due to either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.
5. Currently receiving stable doses of concomitant medications typically prescribed for AS, such as anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and special diets, supplements, or nutritional support for at least 8 weeks prior to the Baseline visit.
6. Legally authorized representative/caregiver(s) agree(s) not to post any of the participant's personal medical data or information related to the study on any website or social media site (e.g., Facebook, Instagram, Twitter, YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed.

Exclusion Criteria

1. Must not have any clinically significant abnormalities in medical history (e.g., major surgery within 3 months of screening), or on physical examination for which treatment with an antisense oligonucleotide (ASO) would be contraindicated or which, in the opinion of the Principal Investigator (PI), could confound the results of this study.
2. Known brain or spinal disease that would interfere with the lumbar puncture (LP) procedure, cerebrospinal fluid (CSF) circulation, or presence of other factors would affect the safety of the LP procedure.
3. Must not have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.
4. Must not have any laboratory abnormalities or any other clinically significant abnormalities that would, as assessed by the Investigator, at screening or Baseline, render a participant unsuitable for inclusion.
5. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid (RNA) \[siRNA\], ASOs) or gene therapy. This exclusion criterion does not apply to coronavirus disease 2019 (COVID-19) vaccinations, which are allowed.
6. Has documented molecular AS confirmation of paternal uniparental disomy or imprinting center defect.
Minimum Eligible Age

2 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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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

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

Children's National Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Children's Mercy

Kansas City, Missouri, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill School of Medicine

Carrboro, North Carolina, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Sydney Children's Hospital

Randwick, , Australia

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada United Kingdom

Central Contacts

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Ionis Pharmaceuticals, Inc.

Role: CONTACT

Phone: (844) 285-7172

Email: [email protected]

Other Identifiers

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2024-519711-33-00

Identifier Type: CTIS

Identifier Source: secondary_id

U1111-1319-2765

Identifier Type: OTHER

Identifier Source: secondary_id

ION582-CS2

Identifier Type: -

Identifier Source: org_study_id