Daniel G Glaze1, Jeffrey L Neul2, Alan Percy3, Tim Feyma4, Arthur Beisang4, Alex Yaroshinsky5, George Stoms5, David Zuchero6, Joseph Horrigan7, Larry Glass8, Nancy E Jones8. 1. Baylor College of Medicine, Houston, Texas. Electronic address: dglaze@bcm.edu. 2. Baylor College of Medicine, Houston, Texas. 3. University of Alabama, Birmingham, Birmingham, Alabama. 4. Gillette Children's Specialty Healthcare, Saint Paul, Minnesota. 5. Vital Systems, Inc., Rolling Meadows, Illinois. 6. Chesapeake Regulatory Group, Inc., Highland, Maryland. 7. University of North Carolina, Chapel Hill, Chapel Hill, North Carolina. 8. Neuren Pharmaceuticals, Ltd., Camberwell, Victoria, Australia.
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.
RCT Entities:
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.
Authors: Melissa Raspa; Carla M Bann; Angela Gwaltney; Timothy A Benke; Cary Fu; Daniel G Glaze; Richard Haas; Peter Heydemann; Mary Jones; Walter E Kaufmann; David Lieberman; Eric Marsh; Sarika Peters; Robin Ryther; Shannon Standridge; Steven A Skinner; Alan K Percy; Jeffrey L Neul Journal: Am J Intellect Dev Disabil Date: 2020-11-01
Authors: Jan-Marino Ramirez; Marlusa Karlen-Amarante; Jia-Der Ju Wang; Nicholas E Bush; Michael S Carroll; Debra E Weese-Mayer; Alyssa Huff Journal: Physiology (Bethesda) Date: 2020-11-01
Authors: Jonathan K Merritt; Bridget E Collins; Kirsty R Erickson; Hongwei Dong; Jeffrey L Neul Journal: Hum Mol Genet Date: 2020-08-29 Impact factor: 6.150
Authors: Clare Cutri-French; Dallas Armstrong; Joni Saby; Casey Gorman; Jane Lane; Cary Fu; Sarika U Peters; Alan Percy; Jeffrey L Neul; Eric D Marsh Journal: Ann Neurol Date: 2020-06-29 Impact factor: 10.422
Authors: Jennifer L Stallworth; Marisela E Dy; Caroline B Buchanan; Chin-Fu Chen; Alexandra E Scott; Daniel G Glaze; Jane B Lane; David N Lieberman; Lindsay M Oberman; Steven A Skinner; Aubin E Tierney; Gary R Cutter; Alan K Percy; Jeffrey L Neul; Walter E Kaufmann Journal: Neurology Date: 2019-05-03 Impact factor: 9.910