UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Double-Blind, Randomized, Placebo-Controlled Study of Trofinetide in Pediatric Rett Syndrome

Glaze, DG; Neul, JL; Kaufmann, WE; Berry-Kravis, E; Condon, S; Stoms, G; Oosterholt, S; ... Percy, AK; + view all (2019) Double-Blind, Randomized, Placebo-Controlled Study of Trofinetide in Pediatric Rett Syndrome. Neurology , 92 (16) e1912-e1925. 10.1212/WNL.0000000000007316. Green open access

[thumbnail of Della Pasqua_e1912.full.pdf]
Preview
Text
Della Pasqua_e1912.full.pdf - Published Version

Download (999kB) | Preview

Abstract

OBJECTIVE: To determine safety, tolerability and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are available. METHODS: This was a Phase 2, multicenter, double-blind, placebo-controlled, parallel group study, in which safety/tolerability, pharmacokinetics, and clinical response to trofinetide were characterized in 82 children/adolescents with RTT, aged 5-15 years. 62 participants were randomized 1:1:1:1 to receive placebo BID for 14 days, followed by placebo, 50 mg/kg, 100 mg/kg or 200 mg/kg BID of trofinetide for 42 days. Following blinded safety data review, 20 additional participants were randomized 1:1 to the 200 mg/kg or placebo BID groups. Safety assessments included adverse events (AEs), clinical laboratory tests, physical examinations and concomitant medications. Clinician- and caregiver-based efficacy measurements assessed clinically relevant, phenotypic dimensions of impairment of RTT. RESULTS: All dose levels were well tolerated and generally safe. Trofinetide at 200 mg/kg BID showed statistically significant and clinically relevant improvements relative to placebo on the Rett Syndrome Behaviour Questionnaire, RTT-Clinician Domain Specific Concerns-Visual Analog Scale, and Clinical Global Impression Scale-Improvement. Exploratory analyses suggested that observed changes correlated with plasma trofinetide exposure. CONCLUSION: These results, together with those from a previous adolescent/adult trial, indicate trofinetide’s potential for treating core RTT symptoms and support further trials. CLASSIFICATION OF EVIDENCE: This study provides class I evidence that for children/adolescents with RTT, trofinetide was safe, well tolerated, and demonstrated improvement over placebo at 200mg/kg BID in functionally important dimensions of RTT.

Type: Article
Title: Double-Blind, Randomized, Placebo-Controlled Study of Trofinetide in Pediatric Rett Syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000007316
Publisher version: https://doi.org/10.1212/WNL.0000000000007316
Language: English
Additional information: Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Keywords: All clinical neurology, All Pediatric, All clinical trials, Clinical trials Randomized controlled, Rett syndrome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10068302
Downloads since deposit
88Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item