Capturing seizures in clinical trials of antiseizure medications for KCNQ2 -DEE.

Autor: Millichap JJ; Epilepsy Center and Division of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.; Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Harden CL; Xenon Pharmaceuticals, Inc., Burnaby, British Columbia, Canada., Dlugos DJ; Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., French JA; Department of Neurology NYU Langone School of Medicine, New York, NY, USA., Butterfield NN; Xenon Pharmaceuticals, Inc., Burnaby, British Columbia, Canada., Grayson C; Xenon Pharmaceuticals, Inc., Burnaby, British Columbia, Canada., Aycardi E; Xenon Pharmaceuticals, Inc., Burnaby, British Columbia, Canada., Pimstone SN; Xenon Pharmaceuticals, Inc., Burnaby, British Columbia, Canada.; Division of General Internal Medicine, University of British Columbia, Burnaby, British Columbia, Canada.
Jazyk: angličtina
Zdroj: Epilepsia open [Epilepsia Open] 2021 Jan 29; Vol. 6 (1), pp. 38-44. Date of Electronic Publication: 2021 Jan 29 (Print Publication: 2021).
DOI: 10.1002/epi4.12466
Abstrakt: Literature review of patients with KCNQ2 developmental and epileptic encephalopathy ( KCNQ2 -DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age- and disease-specific stereotyped seizures. The typical seizure type of KCNQ2 -DEE, focal tonic, starts within 0-5 days of life and is readily captured by video-electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, KCNQ2 -DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Therefore, we propose that the 2019 recommendations from the International League against Epilepsy (ILAE), the Pediatric Epilepsy Research Consortium (PERC), for capturing and recording seizures for clinical trials ( Epilepsia Open , 4, 2019, 537) are suitable for use in KCNQ2 -DEE‒associated antiseizure medicine (ASM) treatment trials. The ILAE/PERC consensus guidance states that a caregiver-maintained seizure diary, completed by caregivers who are trained to recognize seizures using within-patient historical recordings, accurately captures seizures prospectively in a clinical trial. An alternative approach historically endorsed by the Food and Drug Administration (FDA) compares seizure counts captured on VEEG before and after treatment. A major advantage of the ILAE/PERC strategy is that it expands the numbers of eligible patients who meet inclusion criteria of clinical trials while maintaining accurate seizure counts ( Epilepsia Open , 4, 2019, 537). Three recent phase 3 pivotal pediatric trials investigating ASMs to treat syndromic seizures in patients as young as 2 years of age ( N Engl J Med , 17, 2017, 699; Lancet , 21, 2020, 2243; Lancet , 17, 2018, 1085); and ongoing phase 2 open-label pediatric clinical trial that includes pediatric epileptic syndromes as young as 1 month of age ( Am J Med Genet A , 176, 2018, 773), have already used caregiver-maintained seizure diaries successfully. For determining the outcome of a KCNQ2 -DEE ASM treatment trial, the use of a seizure diary to count seizures by trained observers is feasible because the seizures of KCNQ2 -DEE are clinically apparent. This strategy is supported by successful precedent in clinical trials in similar age groups and has the endorsement of the international pediatric epilepsy community.
Competing Interests: Drs. Grayson, Harden, Butterfield, Pimstone, and Aycardi are employed by Xenon Pharmaceuticals Inc (“Xenon”). They receive salaries and may hold stock or stock options in Xenon. Dr Millichap reports personal fees from American Academy of Neurology, personal fees from Up‐To‐Date, personal fees from BMJ Best Practice, grants and personal fees from UCB Pharma, grants and personal fees from Mallinkrodt, personal fees from Esai, personal fees from Biomarin, personal fees from Ionis, personal fees from Greenwich, personal fees from Sunovion, personal fees from Upsher‐Smith, grants from NIH, grants from Citizens United for Research in Epilepsy, personal fees from Praxis, grants and personal fees from Trumacro, outside the submitted work; Pursuant to a Consulting Agreement between Ann and Robert H. Lurie Children's Hospital of Chicago and Xenon, it is anticipated that Dr Millichap will serve as the Global Coordinating Investigator for Xenon's planned Phase 3 study of XEN496. The Ann and Robert H. Lurie Children's Hospital of Chicago receives financial compensation from Xenon in exchange for Dr Millichap's services. In addition, Dr Millichap, in a personal capacity, is a consultant for Xenon and also serves as a member the Xenon Steering Committee for XEN496. Dr Millichap receives financial compensation from Xenon in exchange for his services. Dr French receives NYU salary support from the Epilepsy Foundation and for consulting work and/or attending Scientific Advisory Boards on behalf of the Epilepsy Study Consortium for Acadia, Adamas, Addex, Aeonian, Alexza, Anavex, Arvelle Therapeutics, Inc, Axcella Health, Axovant, Biogen, Biomotiv/Koutif, Blackfynn, Bloom Science, Bridge Valley Ventures, Cavion, Cerebral Therapeutics, Cerevel, Clinilabs, Concert Pharmaceuticals, Covance, Crossject, CuroNZ, Eisai, Empatica, Encoded, Engage Therapeutics, Encoded, Epitel, GW Pharma, Idorsia, Impax, Ionis, J&J Pharmaceuticals, Marinus, MonosolRx, Neurelis, Neurocrine, Novartis, Otsuka Pharmaceutical Development, Ovid Therapeutics Inc, Pfizer, Pfizer‐Neusentis, Praxis, Redpin, Sage, Sancillio, Shire, SK Life Sciences, Springworks, Stoke, Sunovion, Supernus, Takeda, UCB Inc, Ultragenyx, Upsher‐Smith, Vyera, West Therapeutic Development, Xenon, Xeris, Zogenix, and Zynerba. Dr French has also received research grants from Biogen, Cavion, Eisai, Engage, GW Pharma, Lundbeck, Neurelis, Ovid, SK Life Sciences, Sunovion, UCB, and Zogenix as well as grants from the Epilepsy Research Foundation, Epilepsy Study Consortium, and NINDS (#U01‐NS038455). She is on the editorial board of Lancet Neurology and Neurology Today. She is scientific officer for the Epilepsy Foundation for which NYU receives salary support. She has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Adamas, Arvelle Therapeutics, Inc, Axovant, Biogen, Blackfynn, Crossject, CuroNz, Eisai, Engage, Idorsia, Neurelis, Novartis, Otsuka, Ovid, Pfizer, Redpin, Sage, SK Life Science, Sunovion, Takeda, UCB, Ultragenyx, and Zynerba. Dr Dlugos receives salary support from NIH, Commonwealth of Pennsylvania Department of Health, Pediatric Epilepsy Research Foundation, and The Epilepsy Study Consortium. He is an investigator on research grants awarded to CHOP from Zogenix, Greenwich Biosciences, Brain Sentinel, Neurelis, Q‐State, Aquestive, Bio‐Pharm, SK Life Sciences, and Encoded Therapeutics. He has received travel expenses for protocol development conferences or investigator meetings from Marinus, Ovid/Takeda, Ultragenyx, Pfizer, Biogen, BioMarin, and Xenon. He received honoraria and/or travel support for CME and other educational programs from Wake Forest University School of Medicine, American Epilepsy Society, American Academy of Neurology, Epilepsy Foundation of America, Epilepsy Foundation of North Carolina, Medscape, Miller Medical Communications, Ecuador Neurology Project, Ministry of Health of the United Arab Emirates, Seoul National University, and the Chinese Pediatric Society.
(© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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