NCT06914609

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome

Phase 3 Study of the Efficacy and Safety of ION582 in Children and Adults With Angelman Syndrome

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 158 (estimated)
• Sponsor: Ionis Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 2 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of ION582 in children and adults with Angelman syndrome caused by a deletion or mutation of the UBE3A gene.

Detailed description

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 ION582 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 ION582. Participant, Caregiver, Investigator and Sponsor will remain blinded to the ION582 dose administered to participants during the LTE. The study initiated in 2024 with three dosing groups (40 mg ION582, 80 mg ION582, and placebo). Following additional review of data from the ongoing Phase 1/2 trial of ION582 (HALOS), REVEAL was amended in December 2025 to its current form as a two-arm study: 80 mg ION582 and placebo. Following the amendment, participants who were randomized to receive 40 mg ION582 will be transitioned to receive 80 mg ION582.

Conditions

• Angelman Syndrome

Interventions

Type	Name	Description
DRUG	ION582	ION582 will be administered by IT injection.
DRUG	Placebo	ION582 matching placebo will be administered by IT injection.

Timeline

• Start date: 2025-06-10
• Primary completion: 2027-08-01
• Completion: 2030-04-01
• First posted: 2025-04-06
• Last updated: 2026-04-08

Locations

37 sites across 12 countries: United States, Australia, Canada, Germany, Israel, Italy, Japan, Poland, Singapore, South Korea, Spain, United Kingdom

Regulatory

• FDA-regulated drug study