Angelman Syndrome
Conditions
Interventions
ION582 40 mg or 80 mg or placebo, each administered every 12 weeks, delivered via lumbar intrathecal injection.
Sponsors
Junge Candice
Eligibility
Sex/Gender
All
Inclusion criteria
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 documented diagnosis of Angelman syndrome (AS) with molecular confirmation of either a 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. *Not approved for use in Japan. 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.
Exclusion criteria
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 or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed. 6. Has documented molecular AS confirmation of AS due to paternal uniparental disomy or imprinting center defect.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Performance on the Expressive Communication Subdomain Raw Score of the Bayley Scales for Infant and Toddler Development-4 (Bayley-4) in Cohort 1 (aged 2 to <18 years old) | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Fine Motor Subdomain Raw Score Change in Observer-Reported Communication Ability (ORCA): Overall Emerging T score Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Change in Vital Signs and Clinical Laboratory Results | — |
Countries
Argentina, Australia, Belgium, Canada, Colombia, Ireland, Israel, Italy, Japan, Poland, Singapore, South Korea, Spain, United Kingdom, United States
Contacts
Public ContactYuki Nagata
Medpace Japan K.K.
Outcome results
None listed