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Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study

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Yayımlandı:Nature Medicine vol. 29, no. 6 (Jun 2023), p. 1468
Yazar: Neul, Jeffrey L.
Diğer Yazarlar: Percy, Alan K., Benke, Timothy A., Berry-Kravis, Elizabeth M., Glaze, Daniel G., Marsh, Eric D., Lin, Tim, Stankovic, Serge, Bishop, Kathie M., Youakim, James M.
Baskı/Yayın Bilgisi:
Nature Publishing Group
Konular:
Neurodevelopmental disorders
Health services
Proline
Glycine
Growth factors
Placebos
Rett syndrome
Diarrhea
Effectiveness
Behavior
Medicine
Communication
Quarantine
Questionnaires
Ostomy
Coronaviruses
Insulin-like growth factors
Consent
Proteins
Skills
COVID-19
Hospitals
Social
Online Erişim:Citation/Abstract
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Özet:Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine–proline–glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study (<ext-link xlink:href="https://clinicaltrials.gov" ext-link-type="url">https://clinicaltrials.gov</ext-link> identifier <ext-link xlink:href="https://clinicaltrials.gov/ct2/show/NCT04181723?term=NCT04181723&draw=2&rank=1" ext-link-type="url">NCT04181723</ext-link>), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was −4.9 versus −1.7 (P = 0.0175; Cohen’s d effect size, 0.37), and LSM Clinical Global Impression–Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant–Toddler Checklist Social Composite score was −0.1 versus −1.1 (P = 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.Results from the LAVENDER phase 3 study demonstrate that trofinetide, a synthetic analog of glycine–proline–glutamate, provides significant therapeutic benefits in the core symptoms of Rett syndrome
ISSN:1078-8956
1546-170X
DOI:10.1038/s41591-023-02398-1
Kaynak:Science Database