2'-O-(2-METHOXYETHYL) MODIFIED ANTISENSE OLIGONUCLEOTIDE TARGETING UBE3A ANTISENSE TRANSCRIPT RNA for Angelman syndrome

Inclusion criteria

• {"criterion_text":"- 1. The participants caregiver(s)/ legally-authorized representative (LAR) must have given written informed consent and any authorizations required by local law and be able to comply with all study requirements.\n- 2. Medically stable and can undergo sedation and/or general anesthesia without intubation.\n- 3. Male or female between 2 and ≤50 years of age, depending on specific cohort, at the time of the in-clinic Screening visit.\n- 4. Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either a Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.\n- 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.\n- 6. LAR/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

• {"criterion_text":"- 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.\n- 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.\n- 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.\n- 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.\n- 5. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid (RNA) [siRNA], ASOs) or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed.\n- 6. Has molecular confirmation of AS due to paternal uniparental disomy, imprinting defect, or mosaic findings."}

Primary endpoints

• {"endpoint_text":"- 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 [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Expressive Communication subdomain raw score of the Bayley-4 assessed without caregiver input, measured at Baseline and at Week 52."}

Secondary endpoints

• {"endpoint_text":"- 1. Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Cognition Subdomain Raw Score without caregiver input [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Cognition subdomain raw score of Bayley-4 assessed without caregiver input at Baseline and Week 52."}
• {"endpoint_text":"- 2. Change in Symptoms of Angelman Syndrome -Clinician Global Impression of Change (SAS-CGI-C): Overall AS [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Clinician-rated SAS-CGI-C overall assessment of change in Angelman Syndrome symptoms at Baseline and Week 52."}
• {"endpoint_text":"- 3. Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Receptive Communication Subdomain Raw Score [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Receptive Communication subdomain raw score from Vineland-3 at Baseline and Week 52."}
• {"endpoint_text":"- 4. Change in Vineland Adaptive Behavior Scale-3 (Vineland-3): Daily Living Skills, Personal Subdomain Raw Score [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Daily Living Skills, Personal subdomain raw score from Vineland-3 at Baseline and Week 52."}
• {"endpoint_text":"- 5. Change in Symptoms of Angelman Syndrome - Clinician Global Impression of Change (SAS-CGI-C): Sleep Problems [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Clinician-rated SAS-CGI-C assessment specific to sleep problems at Baseline and Week 52."}
• {"endpoint_text":"- 6. Change in Bayley Scales for Infant and Toddler Development-4 (Bayley-4): Fine Motor Subdomain Raw Score without caregiver input [Time Frame: Baseline to Week 52]","definition_or_measurement_approach":"Fine Motor subdomain raw score of Bayley-4 assessed without caregiver input measured from Baseline to Week 52."}
• {"endpoint_text":"- 7. Change in Observer-Reported Communication Ability (ORCA): Overall Emerging T score [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Observer-reported ORCA overall Emerging T score at Baseline and Week 52."}
• {"endpoint_text":"- 8. Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time Frame: Up to Week 52]","definition_or_measurement_approach":"Proportion of participants experiencing TEAEs and SAEs recorded up to Week 52."}
• {"endpoint_text":"- 9. Change in Vital Signs and Clinical Laboratory Results [Time Frame: Baseline and Week 52]","definition_or_measurement_approach":"Changes from Baseline in measured vital signs and clinical laboratory results assessed at Baseline and Week 52."}

Italy

Earliest CTIS Part Ii Submission Date

09-02-2026

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

28

Number Of Sites

4

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

13-02-2026

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

03-02-2026

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

41

Number Of Sites

1

Number Of Participants

4

Poland

Earliest CTIS Part Ii Submission Date

09-02-2026

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

32

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Ionis Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

PK analysis; Pharmacovigilance

Name

Medpace Finland Oy

Responsibilities

Patient Concierge Services (PCS) for patient stipend and travel reimbursement; Central lab for sample storage; other support functions

Name

WCG Clinical Inc.

Responsibilities

eCOA Scales and Translations and Central Vineland Raters

Name

Endpoint Clinical Inc.

Responsibilities

IWRS/IRT

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK analysis; Pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Rehab Metrics","duties_or_roles":"Onsite Bayley rater, as needed","organisation_type":"Health care"}
• {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"UBE3A Genetic Testing Research – Optional","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Clouds of Care","duties_or_roles":"EEG Central Reader","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"CortiCare","duties_or_roles":"EEG (EEG technician and equipment)","organisation_type":"Industry"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"eCOA Scales and Translations and Central Vineland Raters","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Xerimis B.V.","duties_or_roles":"Study Drug Depot for EU","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cogstate Inc.","duties_or_roles":"Rater Qualification & Training","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Informed Medical Decisions Inc.","duties_or_roles":"Central review of genetic reports","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IWRS/IRT","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Patient Concierge Services (PCS) for patient stipend and travel reimbursement; Central lab for sample storage; other study support functions","organisation_type":"Pharmaceutical company"}