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

"reporting summary supplementary data 1 final version of the statistical analysis plan.; supplementary data 2 final version of the study protocol."

"Competing interests J.L.N. has received research funding from the International Rett Syndrome Foundation, the National Institutes of Health and Rett Syndrome Research Trust; and personal consultancy fees from Acadia Pharmaceuticals, Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La Roche, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health and Taysha Gene Therapies and for the preparation of CME activities for Medscape and PeerView Institute; serves on the scientific advisory board of Alcyone Lifesciences; is a scientific cofounder of LizarBio Therapeutics; and was a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. A.K.P. is coeditor of Translational Science of Rare Diseases, received research funding from the National Institutes of Health and is a consultant for Acadia Pharmaceuticals, AveXis, GW Pharmaceuticals and Anavex Life Science as well as an adviser to the International Rett Syndrome Foundation. T.A.B. received research funding from the GRIN2B Foundation, the International Foundation for CDKL5 Research, the Loulou Foundation, the National Institutes of Health and the Simons Foundation; has consultancies for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics and Takeda Pharmaceutical; has clinical trials with Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Ovid Therapeutics and Rett Syndrome Research Trust; all remuneration has been made to his department. E.M.B.-K. has received funding from Acadia Pharmaceuticals, Alcobra Pharmaceuticals, AMO Pharma, Asuragen, AveXis, Biogen, BioMarin, Cydan Development, EryDel, Fulcrum Therapeutics, GeneTx, GW Pharmaceuticals, Ionis Pharmaceuticals, Jaguar Health, Lumos Pharma, Marinus Pharmaceuticals, Neuren Pharmaceuticals, Neurogene, Neurotrope, Novartis, Orphazyme, Ovid Therapeutics, Retrophin, Roche, Seaside Therapeutics, Taysha Gene Therapies, Tetra Bio-Pharma, Ultragenyx, Yamo Pharmaceuticals, Zynerba Pharmaceuticals and Vtesse–Sucampo–Mallinckrodt Pharmaceuticals to consult on trial design or run clinical or laboratory validation trials in genetic neurodevelopmental or neurodegenerative disorders, all of which is directed to Rush University Medical Center in support of rare disease programs; E.M.B.-K. receives no personal funds, and Rush University Medical Center has no relevant financial interest in any of the commercial entities listed. D.G.G. has received personal compensation and research support from Acadia Pharmaceuticals, Neuren Pharmaceuticals and Newron Pharmaceuticals. E.D.M. has received research support from the National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development, the Eagles Autism Foundation, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, the International CDKL5 Research Foundation and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, GW Pharmaceuticals, Zogenix, Acadia Pharmaceuticals and Marinus Pharmaceuticals. He has received personal compensation for consulting from Stoke Therapeutics and Acadia Pharmaceuticals. J.M.Y., K.M.B., S.S. and T.L. are employees of and stockholders in Acadia Pharmaceuticals. S.S. is also a board director and stockholder of Neurogene."

"We thank the trial participants, their families and our fellow investigators involved in this trial: B. Suter (Texas Children’s Hospital, Houston, Texas, US), C. Buhrfiend, P. Heydemann (Rush University Children’s Hospital, Chicago, Illinois, US), S. Standridge, E. Broomall, K. Peariso (Cincinnati Children’s Hospital Medical Center, Division of Neurology and University of Cincinnati, College of Medicine, Department of Pediatrics, Cincinnati, OH, US), C. Fu, S. Peters (Vanderbilt University Medical Center, Nashville, Tennessee, US), R. Haas, N. Guido-Estrada (University of California, San Diego, La Jolla, California, US), S. Kessler, S. Massey (Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, US), A. Ananth (University of Alabama at Birmingham, Birmingham, Alabama, US), R. Ryther, J. Weisenberg (Washington University School of Medicine, Saint Louis, Missouri, US), D. Lieberman, R. Witt, D. Friedman (Boston Children’s Hospital Harvard Medical School, Boston, Massachusetts, US), A. Stratton (Children’s Hospital Colorado, Aurora, Colorado, US), V. Narayanan, N. Belnap (Translational Genomics Research Institute, Phoenix, Arizona, US), R.J. Hagerman, B. Restrepo, M. Jones* (UC Davis MIND Institute, Sacramento, California, US; *investigator passed away before participating in the trial), S.A. Skinner (Greenwood Genetic Center, Greenwood, South Carolina, US), T. Feyma, A. Beisang (Gillette Children’s Specialty Healthcare, Saint Paul, Minnesota, US), A. Djukic (Montefiore Medical Center, Children’s Hospital at Montefiore, Bronx, New York, US), Y. Shiloh-Malawsky, D. Cejas, Z. Fan (the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, US), R. Saneto (Seattle Children’s, Seattle, Washington, US), J. Ranells, A. Sanchez-Valle, C. Griffith, K. Morgan (University of South Florida Children’s Medical Services, Tampa, Florida, US), C. Smith-Hicks, M. Jain (Kennedy Krieger Institute, Clinical Trials Unit, Baltimore, Maryland, US), S. Parikh, G. Hsich (Cleveland Clinic, Cleveland, Ohio, US), A.L. Talboy, R. Sanchez (Emory Genetics Clinical Trial Center, Atlanta, Georgia, US). We also thank K. Raudibaugh, K. O’Rourke-Kosko, C. Murphy and R. Nunez of Acadia Pharmaceuticals. The study was funded by Acadia Pharmaceuticals. The study sponsor (Acadia Pharmaceuticals) contributed to the study design, the writing of the report and the decision to submit the article for publication. Medical writing support was provided by S. Murray, MSc, CMPP, of Evidence Scientific Solutions and funded by Acadia Pharmaceuticals. Data availability: This clinical trial was sponsored by Acadia Pharmaceuticals. Acadia supports data sharing consistent with the Principles for Responsible Clinical Trial Data Sharing and International Committee of Medical Journal Editors’ recommendations. Acadia shares data from completed clinical trials through public registries (https://clinicaltrials.gov), presentation at scientific congresses and through open access in peer-reviewed journals. Clinical study results from this study were submitted to https://clinicaltrials.gov in April 2023. Additional, related information necessary to appraise the quality and robustness of the findings (study protocol, statistical analysis plan) is available in the Supplementary Information. The authors will provide access to individual-deidentified participant-level data that underlie the data presented in this paper, including data dictionaries, the study protocol and other relevant information, to any researcher who provides a methodologically sound proposal for academic purposes to interpret, verify and extend research in the article beginning 6 months and ending 5 years after article publication. Requests for the ‘minimum dataset’ should go through Acadia Medical Information and will be reviewed by the sponsor (Acadia) to verify whether the request is subject to any intellectual property or confidentiality obligations. For additional information, please contact Acadia Medical Information at medicalinformation@acadia-pharm.com. Source data are provided with this paper. Competing interests: J.L.N. has received research funding from the International Rett Syndrome Foundation, the National Institutes of Health and Rett Syndrome Research Trust; and personal consultancy fees from Acadia Pharmaceuticals, Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La Roche, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health and Taysha Gene Therapies and for the preparation of CME activities for Medscape and PeerView Institute; serves on the scientific advisory board of Alcyone Lifesciences; is a scientific cofounder of LizarBio Therapeutics; and was a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. A.K.P. is coeditor of Translational Science of Rare Diseases, received research funding from the National Institutes of Health and is a consultant for Acadia Pharmaceuticals, AveXis, GW Pharmaceuticals and Anavex Life Science as well as an adviser to the International Rett Syndrome Foundation. T.A.B. received research funding from the GRIN2B Foundation, the International Foundation for CDKL5 Research, the Loulou Foundation, the National Institutes of Health and the Simons Foundation; has consultancies for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics and Takeda Pharmaceutical; has clinical trials with Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Ovid Therapeutics and Rett Syndrome Research Trust; all remuneration has been made to his department. E.M.B.-K. has received funding from Acadia Pharmaceuticals, Alcobra Pharmaceuticals, AMO Pharma, Asuragen, AveXis, Biogen, BioMarin, Cydan Development, EryDel, Fulcrum Therapeutics, GeneTx, GW Pharmaceuticals, Ionis Pharmaceuticals, Jaguar Health, Lumos Pharma, Marinus Pharmaceuticals, Neuren Pharmaceuticals, Neurogene, Neurotrope, Novartis, Orphazyme, Ovid Therapeutics, Retrophin, Roche, Seaside Therapeutics, Taysha Gene Therapies, Tetra Bio-Pharma, Ultragenyx, Yamo Pharmaceuticals, Zynerba Pharmaceuticals and Vtesse–Sucampo–Mallinckrodt Pharmaceuticals to consult on trial design or run clinical or laboratory validation trials in genetic neurodevelopmental or neurodegenerative disorders, all of which is directed to Rush University Medical Center in support of rare disease programs; E.M.B.-K. receives no personal funds, and Rush University Medical Center has no relevant financial interest in any of the commercial entities listed. D.G.G. has received personal compensation and research support from Acadia Pharmaceuticals, Neuren Pharmaceuticals and Newron Pharmaceuticals. E.D.M. has received research support from the National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development, the Eagles Autism Foundation, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, the International CDKL5 Research Foundation and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, GW Pharmaceuticals, Zogenix, Acadia Pharmaceuticals and Marinus Pharmaceuticals. He has received personal compensation for consulting from Stoke Therapeutics and Acadia Pharmaceuticals. J.M.Y., K.M.B., S.S. and T.L. are employees of and stockholders in Acadia Pharmaceuticals. S.S. is also a board director and stockholder of Neurogene."