The STARS phase 2 study: a randomized controlled trial of gaboxadol in Angelman syndrome

Objective: To evaluate safety and tolerability and exploratory efficacy
endpoints for gaboxadol (OV101) compared with placebo in individuals with
Angelman syndrome (AS). Methods: Gaboxadol is a highly selective
orthosteric agonist that activates γ-subunit–containing extrasynaptic
γ-aminobutyric acid type A (GABAA) receptors. In a multicenter,
double-blind, placebo-controlled, parallel-group trial, adolescent and
adult individuals with a molecular diagnosis of AS were randomized (1:1:1)
to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose
and gaboxadol 15 mg evening dose (qd); gaboxadol 10 mg morning dose and 15
mg evening dose (bid); or placebo morning and evening dose. Safety and
tolerability were monitored throughout the study. Prespecified exploratory
efficacy endpoints included adapted Clinical Global Impression–Severity
(CGI-S) and Clinical Global Impression–Improvement (CGI-I) scales which
documented the clinical severity at baseline and change after treatment,
respectively. Results: Eighty-eight individuals were randomized. Of 87
individuals (aged 13–45 years) who received at least 1 dose of study drug,
78 (90%) completed the study. Most adverse events (AEs) were mild to
moderate, and no life-threatening AEs were reported. Efficacy of
gaboxadol, as measured by CGI-I improvement in an exploratory analysis,
was observed in gaboxadol qd vs placebo (p = 0.0006). Conclusion: After 12
weeks of treatment, gaboxadol was found to be generally well tolerated
with a favorable safety profile. The efficacy as measured by the
AS-adapted CGI-I scale warrants further studies.