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Current standard of care for the treatment of MPS II is enzyme replacement therapy with intravenous recombinant human iduronate-2-sulfatase (idursulfase). To target cognitive manifestations of MPS II, idursulfase has been formulated for intrathecal administration into the cerebrospinal fluid (idursulfase-IT). In accordance with recommendations for patient-focused drug development, semi-structured interviews were conducted to assess caregiver experiences and observations in a 52-week phase 2\/3 trial\u00a0of idursulfase-IT, in addition to intravenous idursulfase in pediatric patients with neuronopathic MPS II, or a substudy which enrolled patients younger than 3\u00a0years old, all of whom received idursulfase-IT.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, 46 caregivers providing care for 50 children (mean [range] age 7.9 [3\u201317] years at interview) took part in a single 60-min exit interview; six of these children had participated in the substudy. Qualitative and quantitative data were obtained demonstrating the burden of MPS II experienced by caregivers and their families. Following participation in the trials, 39 (78%) of the children were reported by their caregivers to have experienced improvements in the symptoms and impact of disease. Of those with improvements, 37 (95%) experienced cognitive improvements and 26 (67%) experienced emotional\/behavioral improvements. Overall, 43 children (86%) were rated by caregivers as having moderate or severe symptoms before the trials; after the trials, 28 children (56%) were considered to have mild or no symptoms. For the six children who participated in the substudy, these proportions were 83% and 100%, respectively. Caregivers\u2019 qualitative descriptions of trial experiences suggested improvements in children\u2019s verbal and non-verbal functioning and spatial and motor skills, as well as a positive impact on family life.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study revealed caregiver-reported improvements in children\u2019s MPS II symptoms and the impact of the disease on patients and their families. There was a trend for cognitive improvement and a reduction in severity of MPS II symptoms. After many years of extensive review and regulatory discussions of idursulfase-IT, the clinical trial data were found to be insufficient to meet the evidentiary standard to support regulatory filings.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03034-y","type":"journal-article","created":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T23:01:28Z","timestamp":1710111688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2\/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-1435","authenticated-orcid":false,"given":"Karen S.","family":"Yee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Alexanderian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,10]]},"reference":[{"issue":"1\u20132","key":"3034_CR1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ymgme.2020.08.007","volume":"131","author":"JH van der Lee","year":"2020","unstructured":"van der Lee JH, Morton J, Adams HR, Clarke L, Eisengart JB, Escolar ML, et al. 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For all patients, written informed consent was obtained from the parent(s) or legally authorized guardian(s); assent from the patient was also acquired, if applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent to participate and for the interviews to be audio-recorded was obtained from each caregiver prior to interview.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Caregivers provided written consent for transcripts to be made available to the sponsor and included in associated publications.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KSY was an employee of Takeda Development Center Americas, Inc., and stockholder of Takeda Pharmaceuticals Company Limited at the time of study and of the writing of the manuscript (now at Alexion Pharmaceuticals, Inc., AstraZeneca Rare Disease). 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