Ionis Pharmaceuticals has dosed the first subject in the global, randomised Phase III REVEAL trial of investigational ION582, aimed at treating individuals with Angelman syndrome (AS), a rare neurodevelopmental disorder.
The placebo-controlled, double-blind trial will recruit nearly 200 AS adults and children with a maternal UBE3A gene deletion or mutation.
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Over a 52-week treatment period, subjects will be randomised in a 2:1 ratio and given either the therapy or a placebo.
Quarterly doses of either 40 mg or 80 mg of ION582 will be administered to those in the active treatment groups.
After the initial treatment phase, eligible subjects will have the opportunity to enter a long-term extension segment of the trial, where the therapy will be administered for up to two years.
The primary goal of the trial is to assess improvements in expressive communication using the Bayley Scales for Infant and Toddler Development-4 (Bayley-4), a direct clinician-administered assessment tool.
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By GlobalDataExpressive communication deficits are notably the most burdensome symptoms for caregivers of individuals with AS.
The trial will also evaluate secondary endpoints, including overall disease severity, communication, cognition, motor functioning, sleep, and daily living skills, as well as other exploratory endpoints.
ION582 has previously shown promise in the multiple ascending dose (MAD) portion of the Phase I/II open-label HALOS trial, demonstrating clinical improvement across various functional domains such as cognition, motor function, and communication.
The RNA-targeted antisense medicine, ION582, works by inhibiting the expression of the UBE3A antisense transcript (UBE3A-ATS) to potentially increase the UBE3A protein production, to treat AS.
Ionis Pharmaceuticals neurology senior vice-president Holly Kordasiewicz: “This placebo-controlled study will evaluate ION582 in both children and adults with either UBE3A deletion or mutation and builds on earlier encouraging findings from our Phase I/II HALOS study.
“With ION582, we continue to advance our leading wholly owned neurology pipeline, which includes eight medicines in clinical development across a range of rare and more prevalent diseases.”
Last year, Ionis announced the design for the Phase III trial of ION582 for the treatment of AS, following discussions with the US Food and Drug Administration (FDA).
