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

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Pubblicato in:Nature Medicine vol. 29, no. 6 (Jun 2023), p. 1468
Autore principale: Neul, Jeffrey L.
Altri autori: 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.
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024 7 |a 10.1038/s41591-023-02398-1  |2 doi 
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100 1 |a Neul, Jeffrey L.  |u Vanderbilt University Medical Center, Vanderbilt Kennedy Center, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
245 1 |a Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study 
260 |b Nature Publishing Group  |c Jun 2023 
513 |a Evidence Based Healthcare Journal Article 
520 3 |a 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 
653 |a Neurodevelopmental disorders 
653 |a Health services 
653 |a Proline 
653 |a Glycine 
653 |a Growth factors 
653 |a Placebos 
653 |a Rett syndrome 
653 |a Diarrhea 
653 |a Effectiveness 
653 |a Behavior 
653 |a Medicine 
653 |a Communication 
653 |a Quarantine 
653 |a Questionnaires 
653 |a Ostomy 
653 |a Coronaviruses 
653 |a Insulin-like growth factors 
653 |a Consent 
653 |a Proteins 
653 |a Skills 
653 |a COVID-19 
653 |a Hospitals 
653 |a Social 
700 1 |a Percy, Alan K.  |u University of Alabama at Birmingham, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187) 
700 1 |a Benke, Timothy A.  |u Children’s Hospital of Colorado and University of Colorado School of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
700 1 |a Berry-Kravis, Elizabeth M.  |u Rush University Medical Center, Chicago, USA (GRID:grid.240684.c) (ISNI:0000 0001 0705 3621) 
700 1 |a Glaze, Daniel G.  |u Texas Children’s Hospital and Baylor College of Medicine, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
700 1 |a Marsh, Eric D.  |u Children’s Hospital of Philadelphia, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770) 
700 1 |a Lin, Tim  |u Acadia Pharmaceuticals Inc., San Diego, USA (GRID:grid.417646.6) (ISNI:0000 0004 0407 8796) 
700 1 |a Stankovic, Serge  |u Acadia Pharmaceuticals Inc., San Diego, USA (GRID:grid.417646.6) (ISNI:0000 0004 0407 8796) 
700 1 |a Bishop, Kathie M.  |u Acadia Pharmaceuticals Inc., San Diego, USA (GRID:grid.417646.6) (ISNI:0000 0004 0407 8796) 
700 1 |a Youakim, James M.  |u Acadia Pharmaceuticals Inc., San Diego, USA (GRID:grid.417646.6) (ISNI:0000 0004 0407 8796) 
773 0 |t Nature Medicine  |g vol. 29, no. 6 (Jun 2023), p. 1468 
786 0 |d ProQuest  |t Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/2828554641/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/2828554641/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch