Abstract
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.
Keywords
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Article info
Publication history
Published online: July 07, 2017
Accepted:
July 1,
2017
Received in revised form:
June 29,
2017
Received:
April 19,
2017
Footnotes
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.
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.
Identification
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© 2017 Elsevier Inc. All rights reserved.
