Recruiting
Phase 3
REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
Condition(s) studied
Angelman Syndrome
Investigational drug(s) / intervention(s)
obudanersenPlacebo
obudanersen: obudanersen will be administered by IT injection.
Placebo: obudanersen matching placebo will be administered by IT injection.
Study summary
The purpose of this study is to evaluate the efficacy and safety of obudanersen in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene.
Eligibility
Key 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 clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of 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, X (formerly Twitter), YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed.
Key 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) gene therapy or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed.
6. Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings.
Other inclusion/exclusion criteria may apply.
Primary outcome measure(s)
- 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 — Baseline and Week 52
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.
Trial sites (41)
| Facility | City | Region | Status |
| Cedars-Sinai Medical Center |
Los Angeles |
California |
Recruiting |
| UCLA Clinical & Translational Research Center (CTRC) |
Los Angeles |
California |
Recruiting |
| Rady Children's Hospital |
San Diego |
California |
Recruiting |
| Colorado Children's Hospital Research Institute |
Aurora |
Colorado |
Recruiting |
| Children's National Hospital |
Washington D.C. |
District of Columbia |
Recruiting |
| Nicklaus Children's Hospital |
Miami |
Florida |
Recruiting |
| Children's Healthcare of Atlanta |
Atlanta |
Georgia |
Recruiting |
| Rush University Medical Center |
Chicago |
Illinois |
Recruiting |
| Boston Children's Hospital |
Boston |
Massachusetts |
Recruiting |
| Children's Mercy |
Kansas City |
Missouri |
Recruiting |
| Ichan School of Medicine at Mount Sinai |
New York |
New York |
Recruiting |
| Columbia University Irving Medical Center |
New York |
New York |
Recruiting |
| University of North Carolina at Chapel Hill School of Medicine |
Carrboro |
North Carolina |
Recruiting |
| Cincinnati Children's Hospital |
Cincinnati |
Ohio |
Recruiting |
| Nationwide Children's Hospital |
Columbus |
Ohio |
Recruiting |
| Children's Hospital of Philadelphia |
Philadelphia |
Pennsylvania |
Recruiting |
| Vanderbilt Clinical Research Center |
Nashville |
Tennessee |
Recruiting |
| Texas Children's Hospital |
Houston |
Texas |
Recruiting |
| Queensland Children's Hospital |
South Brisbane |
Queensland |
Recruiting |
| Austin Hospital |
Heidelberg |
Australia |
Recruiting |
| Perth Children's Hospital |
Nedlands |
Australia |
Recruiting |
| Sydney Children's Hospital |
Randwick |
Australia |
Recruiting |
| London Health Science Centre - Children's Hospital |
London |
Ontario |
Recruiting |
| McGill University Health Centre |
Montreal |
Quebec |
Recruiting |
| University of Alberta Hospital |
Edmonton |
Canada |
Recruiting |
| British Columbia Children's Hospital |
Vancouver |
Canada |
Recruiting |
| Klinikum der Ludwig-Maximilians-Universitaet Muenchen |
München |
Germany |
Recruiting |
| Sheba Medical Center |
Ramat Gan |
Israel |
Recruiting |
| Fondazione IRCCS Istituto Neurologico Carlo Besta |
Milan |
Italy |
Recruiting |
| Azienda Ospedaliero Universitaria Pisana |
Pisa |
Italy |
Recruiting |
| Ospedale Pediatrico Bambino Gesù |
Roma |
Italy |
Recruiting |
| Osaka Women's and Children's Hospital |
Izumi |
Osaka |
Recruiting |
| National Center of Neurology and Psychiatry |
Kodaira |
Tokyo |
Recruiting |
| Uniwersyteckie Centrum Kliniczne |
Gdansk |
Poland |
Recruiting |
| KK Women's and Children's Hospital |
Singapore |
Singapore |
Recruiting |
| Seoul National University Hospital |
Seoul |
South Korea |
Recruiting |
| Samsung Medical Center |
Seoul |
South Korea |
Recruiting |
| Hospital Sant Joan de Deu |
Barcelona |
Spain |
Recruiting |
| Corporacio Sanitaria Parc Tauli - Hospital de Sabadell |
Sabadell |
Spain |
Recruiting |
| Great Ormond Street Hospital for Children - NHS Foundation Trust |
London |
United Kingdom |
Recruiting |
+ 1 more sites — see the full list on the official registry below.