Gaboxadol in angelman syndrome: A double-blind, parallel-group, randomized placebo-controlled phase 3 study

Christopher Keary*, Lynne M. Bird, Marie Claire de Wit, Shivkumar Hatti, Gali Heimer, Helen Heussler, Alexander Kolevzon, Adera Mathews, Cesar Ochoa-Lubinoff, Wen Hann Tan, Ying Yan, Maxwell Adams

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To evaluate efficacy and safety of gaboxadol for treatment of children with Angelman syndrome (AS). Method: In this international, double-blind, phase 3 trial, we randomized children 4–12 years old with a molecular diagnosis of AS and a Clinical Global Impression (CGI)-severity score ≥3 to either daily administration of weight-based gaboxadol or matching placebo for 12 weeks. The primary endpoint was the CGI-Improvement-AS (CGI-I-AS) score at week 12. Secondary endpoints included the proportion of participants with CGI-I-AS response of ≤3 (i.e., at least “minimal improvement”) and ≤2 (i.e., at least “much improvement”) at week 12. Safety and tolerability were monitored throughout the study. Weight based dosing of study drug ranged from 0.125 mg/kg to 0.24 mg/kg depending on weight range. Results: Between August 2019 and November 2020, 104 participants were enrolled: participants 4–12 years old were randomly (1:1) assigned to gaboxadol (n = 47) or placebo (n = 50), and 7 other participants 2─3 years old who received gaboxadol and were assessed for safety only. All gaboxadol-treated participants and 48 of 50 placebo-treated participants completed treatment. There was no significant difference in CGI-I-AS between groups: at week 12, mean CGI-I-AS score was 3.3 (SD, 1.00) and 3.2 (SD, 1.05) in the gaboxadol and placebo groups, respectively, yielding a least squares mean difference of zero (p = 0.83). There were no between-group significant differences with respect to CGI-I-AS responses. Gaboxadol was well tolerated in all age groups of this study. Conclusions: There was no significant difference in CGI-I-AS between gaboxadol and placebo after 12 weeks of study treatment in pediatric AS participants. Clinicaltrials.gov: NCT04106557.

Original languageEnglish
Pages (from-to)6-12
Number of pages7
JournalEuropean Journal of Paediatric Neurology
Volume47
DOIs
StatePublished - Nov 2023

Keywords

  • Angelman syndrome
  • Gaboxadol
  • Neuronal ubiquitin protein ligase E3A

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