REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome
Phase 3 Study of the Efficacy and Safety of ION582 in Children and Adults With Angelman Syndrome
3 other identifiers
interventional
158
12 countries
38
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jun 2025
Longer than P75 for phase_3
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 22, 2025
CompletedFirst Posted
Study publicly available on registry
April 6, 2025
CompletedStudy Start
First participant enrolled
June 10, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2030
April 29, 2026
April 1, 2026
2.1 years
March 22, 2025
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Performance on the Expressive Communication Subdomain Raw Score of the Bayley Scales for Infant and Toddler Development-4 (Bayley-4) Without Caregiver Input in Cohort 1
The Bayley-4 is a performance-based assessment of developmental functioning across communication, cognition, and motor skills. The expressive communication subdomain of communication measures preverbal and verbal communication. The total raw score reflects the sum of all the item scores within the expressive communication subdomain, with higher scores reflecting greater expressive communication ability.
Baseline and Week 52
Secondary Outcomes (9)
Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Without Caregiver Input
Baseline and Week 52
Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS
Baseline and Week 52
Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score
Baseline and Week 52
Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score
Baseline and Week 52
Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems
Baseline and Week 52
- +4 more secondary outcomes
Study Arms (4)
Cohort 1 ION582 80 mg
EXPERIMENTALParticipants (aged 2 to \<18 years old) will be administered ION582 80 mg via IT injection Q12W during the double blind and LTE treatment periods.
Cohort 1 Placebo
PLACEBO COMPARATORParticipants (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.
Cohort 2 ION582 80 mg
EXPERIMENTALParticipants (aged 18 to ≤50 years old) will be administered ION582 80 mg via IT injection Q12W during the double blind and LTE treatment periods.
Cohort 2 Placebo
PLACEBO COMPARATORParticipants (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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- Medically stable and can undergo sedation and/or general anesthesia without intubation.
- 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.
- Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.
- 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.
- 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, X (formerly Twitter), YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed.
You may not qualify if:
- 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.
- 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.
- Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (38)
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Rady Children's Hospital
San Diego, California, 92123, United States
Colorado Children's Hospital Research Institute
Aurora, Colorado, 80045, United States
Children's National Hospital
Washington D.C., District of Columbia, 20011, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Children's Mercy
Kansas City, Missouri, 64108, United States
Ichan School of Medicine at Mount Sinai
New York, New York, 10029, United States
University of North Carolina at Chapel Hill School of Medicine
Carrboro, North Carolina, 27510, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt Clinical Research Center
Nashville, Tennessee, 37232, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Perth Children's Hospital
Nedlands, 6009, Australia
Sydney Children's Hospital
Randwick, 2031, Australia
London Health Science Centre - Children's Hospital
London, Ontario, N6A 5W9, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
University of Alberta Hospital
Edmonton, T6G 2B7, Canada
British Columbia Children's Hospital
Vancouver, V6H 3V4, Canada
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
München, 81377, Germany
Sheba Medical Center
Ramat Gan, 5265601, Israel
Associazione La Nostra Famiglia - IRCCS Eugenio Medea
Conegliano, 31015, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Ospedale Pediatrico Bambino Gesù
Roma, 00165, Italy
Osaka Women's and Children's Hospital
Izumi, Osaka, 594-1101, Japan
National Center of Neurology and Psychiatry
Kodaira, Tokyo, 187-8551, Japan
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
KK Women's and Children's Hospital
Singapore, 229899, Singapore
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital Sant Joan de Deu
Barcelona, 08950, Spain
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
Sabadell, 08208, Spain
Great Ormond Street Hospital for Children - NHS Foundation Trust
London, WC1N 3JH, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 22, 2025
First Posted
April 6, 2025
Study Start
June 10, 2025
Primary Completion (Estimated)
August 1, 2027
Study Completion (Estimated)
April 1, 2030
Last Updated
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.