Actively Recruiting
Phase 3 Study of the Efficacy and Safety of ION582 in Children and Adults With Angelman Syndrome
Led by Ionis Pharmaceuticals, Inc. · Updated on 2026-05-15
158
Participants Needed
38
Research Sites
139 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the efficacy and safety of ION582 in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene. This Phase 3, randomized, double-blind, placebo-controlled study includes two age cohorts: children aged 2 to under 18 years and adults aged 18 to 50 years. The study aims to assess how ION582 affects communication and other developmental skills in people with Angelman syndrome. The study has four periods: a screening period up to 28 days, a 60-week double-blind treatment period where participants receive either 80 mg ION582 or a matching placebo via intrathecal injection every 12 weeks, followed by a 25-month long-term extension where all participants receive ION582, and finally an 8-month post-treatment follow-up. Participants completing the placebo-controlled phase can join the extension, with dosing blinded during that time. The study originally included a 40 mg dose group that was later transitioned to 80 mg ION582. During the study, participants will undergo multiple assessments including developmental scales like the Bayley Scales for Infant and Toddler Development and Vineland Adaptive Behavior Scale, along with clinician impressions of Angelman syndrome symptoms. Safety will be monitored through adverse event tracking, vital signs, and lab tests. The primary outcome measures changes in expressive communication over 52 weeks. Overall participation lasts over three years, with regular evaluations to understand the treatment's impact and safety.
CONDITIONS
Brief Title
REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Caregiver or legally authorized representative has provided written informed consent and can comply with study requirements
- Medically stable and able to undergo sedation or general anesthesia without intubation
- Male or female aged between 2 and 50 years, depending on cohort
- Clinical diagnosis of Angelman syndrome with molecular confirmation of UBE3A deletion or mutation
- On stable doses of medications typically used for Angelman syndrome, including anti-epileptics, behavioral or sleep medications, gabapentin, cannabidiol, special diets, supplements, or nutritional support for at least 8 weeks before baseline
- Caregivers agree not to post participant's personal medical data or study information on social media until study completion
You will not qualify if you...
- Clinically significant medical abnormalities or recent major surgery within 3 months that contraindicate antisense oligonucleotide treatment or could affect study results
- Known brain or spinal disease interfering with lumbar puncture or cerebrospinal fluid circulation
- Any other conditions deemed unsuitable by the investigator that interfere with participation or study completion
- Laboratory or clinically significant abnormalities at screening or baseline making participation unsuitable
- Previous treatment with oligonucleotide therapies, gene therapy, or gene editing (except approved nucleic acid-based vaccines)
- Molecular confirmation of Angelman syndrome due to paternal uniparental disomy, imprinting center defect, or mosaicism
- Other criteria as determined by the study team
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 60 weeks
Participants receive ION582 or placebo via intrathecal injection every 12 weeks during the double-blind placebo-controlled treatment period.
Visits every 12 weeks for dosing during the treatment period
Duration - Approximately 25 months
Participants who complete the double-blind period transition to the Long-Term Extension (LTE) treatment period, receiving ION582 every 12 weeks.
Visits every 12 weeks for dosing during the LTE period
Duration - Approximately 8 months
Participants are monitored after completing the LTE treatment period during the post-LTE follow-up phase.
Periodic visits during the follow-up period
Trial Site Locations
Total: 38 locations
1
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Actively Recruiting
2
Rady Children's Hospital
San Diego, California, United States, 92123
Actively Recruiting
3
Colorado Children's Hospital Research Institute
Aurora, Colorado, United States, 80045
Actively Recruiting
4
Children's National Hospital
Washington D.C., District of Columbia, United States, 20011
Actively Recruiting
5
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
Actively Recruiting
6
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30329
Actively Recruiting
7
Rush University Medical Center
Chicago, Illinois, United States, 60612
Actively Recruiting
8
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
9
Children's Mercy
Kansas City, Missouri, United States, 64108
Actively Recruiting
10
Ichan School of Medicine at Mount Sinai
New York, New York, United States, 10029
Actively Recruiting
11
University of North Carolina at Chapel Hill School of Medicine
Carrboro, North Carolina, United States, 27510
Actively Recruiting
12
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Actively Recruiting
13
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
14
Vanderbilt Clinical Research Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
15
Texas Children's Hospital
Houston, Texas, United States, 77030
Actively Recruiting
16
Queensland Children's Hospital
South Brisbane, Queensland, Australia, 4101
Actively Recruiting
17
Perth Children's Hospital
Nedlands, Australia, 6009
Actively Recruiting
18
Sydney Children's Hospital
Randwick, Australia, 2031
Actively Recruiting
19
London Health Science Centre - Children's Hospital
London, Ontario, Canada, N6A 5W9
Actively Recruiting
20
McGill University Health Centre
Montreal, Quebec, Canada, H4A 3J1
Actively Recruiting
21
University of Alberta Hospital
Edmonton, Canada, T6G 2B7
Actively Recruiting
22
British Columbia Children's Hospital
Vancouver, Canada, V6H 3V4
Actively Recruiting
23
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
München, Germany, 81377
Actively Recruiting
24
Sheba Medical Center
Ramat Gan, Israel, 5265601
Actively Recruiting
25
Associazione La Nostra Famiglia - IRCCS Eugenio Medea
Conegliano, Italy, 31015
Not Yet Recruiting
26
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, Italy, 20133
Actively Recruiting
27
Azienda Ospedaliero Universitaria Pisana
Pisa, Italy, 56126
Actively Recruiting
28
Ospedale Pediatrico Bambino Gesù
Roma, Italy, 00165
Actively Recruiting
29
Osaka Women's and Children's Hospital
Izumi, Osaka, Japan, 594-1101
Actively Recruiting
30
National Center of Neurology and Psychiatry
Kodaira, Tokyo, Japan, 187-8551
Actively Recruiting
31
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-952
Actively Recruiting
32
KK Women's and Children's Hospital
Singapore, Singapore, 229899
Actively Recruiting
33
Seoul National University Hospital
Seoul, South Korea, 03080
Actively Recruiting
34
Samsung Medical Center
Seoul, South Korea, 06351
Actively Recruiting
35
Hospital Sant Joan de Deu
Barcelona, Spain, 08950
Actively Recruiting
36
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
Sabadell, Spain, 08208
Actively Recruiting
37
Great Ormond Street Hospital for Children - NHS Foundation Trust
London, United Kingdom, WC1N 3JH
Actively Recruiting
38
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Actively Recruiting
Research Team
I
Ionis Pharmaceuticals, Inc.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here