A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome - 07/11/17
, Jeffrey. L. Neul, MD, PhD a, 1, Alan Percy, MD b, Tim Feyma, MD c, Arthur Beisang, MD c, Alex Yaroshinsky, PhD d, George Stoms, BS d, David Zuchero, MS, JD e, Joseph Horrigan, MD f, Larry Glass, BA g, Nancy E. Jones, PhD gAbstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Rett syndrome, trofinetide, double-blind, placebo-controlled, treatment
Plan
| Author contributions: DG, JN, JH, LG conceived the study and JH and LG designed the study. AY and GS provided statistical advice and analyzed the data. AY, GS, NJ, JH, LG, DG, AP, and JN interpreted the data. DZ, JH, LG, and NJ drafted the manuscript. DG, AP, JN, AB, and TF provided critical revision on the manuscript. DG takes responsibility for the article as a whole. |
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| Potential conflicts of interest: DG, JN, AP, TF, and AB were participating investigators in the Neuren trofinetide clinical trial. DZ and AY were consultants of Neuren Pharmaceuticals at the time of the study. JH was an executive at Neuren Pharmaceuticals at the time of the study. NJ and LG are executives of Neuren Pharmaceuticals. GS is a consultant to Neuren Pharmaceuticals. |
Vol 76
P. 37-46 - novembre 2017 Retour au numéro
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