A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: This study aimed to determine the safety and tolerability of trofinetide and to evaluate efficacy measures in adolescent and adult females with Rett syndrome, a serious and debilitating neurodevelopmental condition for which no therapies are available for its core features. METHODS: This was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, dose-escalation study of the safety and tolerability of trofinetide in 56 adolescent and adult females with Rett syndrome. Subjects were randomly assigned in a 2:1 ratio to 35 mg/kg twice daily of trofinetide or placebo for 14 days; 35 mg/kg twice daily or placebo for 28 days; or 70 mg/kg twice daily or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant, phenotypic dimensions of impairment associated with Rett syndrome. RESULTS: Both 35 mg/kg and 70 mg/kg dose levels of trofinetide were well tolerated and generally safe. Trofinetide at 70 mg/kg demonstrated efficacy compared with placebo based on prespecified criteria. CONCLUSION: Trofinetide was well tolerated in adolescent and adult females with Rett syndrome. Although this study had a relatively short duration in a small number of subjects with an advanced stage of disease, consistent efficacy trends at the higher dose were observed in several outcome measures that assess important dimensions of Rett syndrome. These results represented clinically meaningful improvement from the perspective of the clinicians as well as the caregivers.

Full Text

Duke Authors

Cited Authors

  • Glaze, DG; Neul, JL; Percy, A; Feyma, T; Beisang, A; Yaroshinsky, A; Stoms, G; Zuchero, D; Horrigan, J; Glass, L; Jones, NE

Published Date

  • November 2017

Published In

Volume / Issue

  • 76 /

Start / End Page

  • 37 - 46

PubMed ID

  • 28964591

Electronic International Standard Serial Number (EISSN)

  • 1873-5150

Digital Object Identifier (DOI)

  • 10.1016/j.pediatrneurol.2017.07.002


  • eng

Conference Location

  • United States