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ACTIVE NOT RECRUITINGPhase3

REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome

Sponsor: Ionis Pharmaceuticals, Inc.

NCT ID: NCT06914609

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
obudanersen (drug), Placebo (drug)
How long the study runs
Study runs about 58 months (dates as stated)
About the drug or intervention
obudanersen — drug: obudanersen will be administered by IT injection. · Placebo — drug: obudanersen matching placebo will be administered by IT injection.
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
2 Years to 50 Years
Who
All
Number of participants
156
Started
2025-06-10
Last checked
2026-09

Plain English Summary

What is this study?

  • • Testing a new treatment for angelman syndrome
  • • Phase3 - 156 participants
  • • 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

Who can take part?

  • • Ages 2 Years to 50 Years
  • • Diagnosed with angelman syndrome

Where?

  • • London - Great Ormond Street Hospital for Children - NHS Foundation Trust
  • • Oxford - John Radcliffe Hospital

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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.

More detail

This is a Phase 3, randomized, double-blind, placebo-controlled study in people with Angelman syndrome. The study will consist of 4 periods: a screening period of up to 28 days, an approximate 60-week double blind, placebo-controlled treatment period, followed by an approximate 25-month Long-Term Extension (LTE) treatment period, and an approximate 8-month Post-LTE follow-up period. The study will be comprised of 2 cohorts. Cohort 1 will include pediatric participants, aged 2 to less than (\<)18 years old and serve as the population for evaluation of primary and secondary outcome measures; Cohort 2 will include adult participants, aged 18 to ≤50 years old. Participants will be randomized 1:1 to 80 mg obudanersen or placebo during the double-blind placebo-controlled treatment period. Participants from both cohorts completing the placebo-controlled treatment period will be eligible to transition into the LTE Treatment Period wherein all trial participants will receive obudanersen. Participant, Caregiver, Investigator and Sponsor will remain blinded to the obudanersen dose administered to participants during the LTE. The study initiated in 2024 with three dosing groups (40 mg obudanersen, 80 mg obudanersen, and placebo). Following additional review of data from the ongoing Phase 1/2 trial of obudanersen (HALOS), REVEAL was amended in December 2025 to its current form as a two-arm study: 80 mg obudanersen and placebo. Following the amendment, participants who were randomized to receive 40 mg obudanersen will be transitioned to receive 80 mg obudanersen.

Angelman Syndrome

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What we know so far

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 2 Years - 50 Years
  • Who can join: All genders

What the study is looking for

  • ✓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...
  • ✓Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either...

Who cannot take part

  • ✗Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings.
  • ✗Other inclusion/exclusion criteria may apply.
See the full criteria
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.

Where Is This Study? (2 UK sites)

Great Ormond Street Hospital for Children - NHS Foundation Trust

London WC1N 3JH, United Kingdom

Hospital R&D contact (matched)

Main Email: Research.Governance@gosh.nhs.uk

Research.Governance@gosh.nhs.uk0207 905 2700

John Radcliffe Hospital

Oxford OX3 9DU, United Kingdom

Data sourced from ClinicalTrials.gov · Last verified: 2026-09