dc.contributor.author | Neul, Jeffrey L. | |
dc.contributor.author | Peters, Sarika | |
dc.date.accessioned | 2020-08-24T18:26:42Z | |
dc.date.available | 2020-08-24T18:26:42Z | |
dc.date.issued | 2019-04-16 | |
dc.identifier.citation | Glaze, D. G., Neul, J. L., Kaufmann, W. E., Berry-Kravis, E., Condon, S., Stoms, G., Oosterholt, S., Della Pasqua, O., Glass, L., Jones, N. E., Percy, A. K., & Rett 002 Study Group (2019). Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology, 92(16), e1912–e1925. https://doi.org/10.1212/WNL.0000000000007316 | en_US |
dc.identifier.issn | 0028-3878 | |
dc.identifier.uri | http://hdl.handle.net/1803/15560 | |
dc.description | Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550498/ | en_US |
dc.description.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 to 15 years. Sixty-two participants were randomized 1:1:1:1 to receive placebo twice a day (bid) for 14 days, followed by placebo, 50, 100, 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, 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 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 200 mg/kg bid in functionally important dimensions of RTT. | en_US |
dc.description.sponsorship | The clinical trial was sponsored by Neuren Pharmaceuticals and funded by Neuren Pharmaceuticals and Rettsyndrome.org. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Neurology | en_US |
dc.rights | 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-No Derivatives 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. | |
dc.source.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550498/ | |
dc.source.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550498/ | |
dc.title | Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1212/WNL.0000000000007316 | |