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A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome
Open accessAbstract
BACKGROUND: We analyze the safety and tolerability of trofinetide and provide a preliminary evaluation of its efficacy in adolescent and adult males with fragile X syndrome. METHODS: This study was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, parallel group study of the safety and tolerability of orally administered trofinetide in 72 adolescent and adult males with fragile X syndrome. Subjects were randomly assigned in a 1:1:1 ratio to 35 or 70 mg/kg twice daily trofinetide 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 fragile X syndrome. RESULTS: Both 35 and 70 mg/kg dose levels of trofinetide were well tolerated and appeared to be generally safe. Trofinetide at the 70 mg/kg dose level demonstrated efficacy compared with placebo based on prespecified criteria. On the basis of a permutation test, the probability of a false-positive outcome for the achieved prespecified success was 0.045. In the group analysis, improvement from treatment baseline was demonstrated on three fragile X syndrome-specific outcome measures. CONCLUSIONS: Trofinetide was well tolerated in adolescent and adult males with fragile X syndrome. Despite the relatively short duration of the study, a consistent signal of efficacy at the higher dose was observed in both caregiver and clinician assessments, based on a novel analytical model incorporating evaluation of multiple key symptom areas of fragile X syndrome. This finding suggests a potential for trofinetide treatment to provide clinically meaningful improvement in core fragile X syndrome symptoms.
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“Results demonstrated that the 70 mg/kg/day was significantly beneficial compared to placebo with a permutation test utilizing the primary components of the Fragile X Syndrome Rating Scale, a Fragile X Specific Domain Scale on a visual analogue format, and the ABCFX.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [138]
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Metadata
- Authors
- Berry-Kravis, E., Horrigan, J. P., Tartaglia, N., Hagerman, R., Kolevzon, A., Erickson, C. A., Hatti, S., Snape, M., Yaroshinsky, A., Stoms, G., Sanders, K., Frazier, J., Challman, T., Innis, J., King, B., Cubells, J., Visootsak, J., Skinner, S., Treadwell-Deering, D., Vinson, S. S., Needelman, H., Glass, L., & Jones, N. E.
- Affiliations
- Duke University (US)
- Children's Hospital Colorado (US)
- University of California, Davis (US)
- Mount Sinai Hospital (US)
- Cincinnati Children's Hospital Medical Center (US)
- Suburban Research Associates (US)
- AMO Pharma (United Kingdom) (GB)
- ORCID
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 110
- Pages
- 30-41
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W2734032654
- Cited by
- 102
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 25 · 2023: 18 · 2022: 12 · 2021: 13 · 2020: 15
- FWCI
- 8.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pediatric Neurology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Neuren Pharmaceuticals, Ltd
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- trofinetide, fragile X syndrome, FMRP, safety and tolerability, efficacy, symptom domains, dose comparison
- MeSH terms
- Adolescent, Adult, Child, Double-Blind Method, Fragile X Syndrome, Glutamates, Humans, Male, Outcome Assessment, Health Care, Young Adult
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