{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T22:41:39Z","timestamp":1774392099415,"version":"3.50.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is a newly identified condition with an estimated worldwide prevalence of &lt;\u2009100 patients. Patient interviews can ensure that what is important to patients is assessed in a clinical trial program. Due to the rare and potentially fatal nature of CHAPLE disease, interviews were conducted as part of the pozelimab clinical trial, rather than in a separate study before the trial. The aim of the interviews was to identify the key disease-related signs, symptoms, and health-related quality-of-life (HRQoL) impacts that are important and relevant to patients with CHAPLE disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Interviews were conducted with patients and\/or caregivers at two timepoints (screening and Week 24) during the pozelimab trial to document the signs\/symptoms and HRQoL impacts of CHAPLE disease, and document the most bothersome sign\/symptom at screening. At Week 24, interviews gathered additional information on the patient experience from caregivers and patients (note: the impact of pozelimab treatment was also collected, though these results are presented elsewhere).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Ten patients, aged 3\u201319 years, were enrolled in the trial; caregivers contributed to nine interviews. Thirty-one signs\u200c\/symptoms and 65 HRQoL impacts were reported during the interviews. Abdominal pain, diarrhea, facial and peripheral edema\/\u200cswelling, nausea, and vomiting emerged as the core signs\/\u200csymptoms of CHAPLE disease (i.e., experienced by \u2265\u200990% of patients prior to treatment). The remaining 25 signs\/symptoms were experienced by four or fewer (<jats:italic>n<\/jats:italic>\u2009\u2264\u20094, \u2264\u200940.0%) patients, and 15 were only reported by one patient each. Abdominal pain and facial edema were reported as the most bothersome signs\/\u200csymptoms (<jats:italic>n<\/jats:italic>\u2009=\u20099, 90.0% and <jats:italic>n<\/jats:italic>\u2009=\u20091, 10.0%, respectively). The most frequently reported (i.e., \u2265\u200980% of interviews) HRQoL impacts were restricted diet (<jats:italic>n<\/jats:italic>\u2009=\u200910, 100.0%), sleep disruptions (<jats:italic>n<\/jats:italic>\u2009=\u200910, 100.0%), missing school (<jats:italic>n<\/jats:italic>\u2009=\u20099, 90.0%), ability to get dressed independently (<jats:italic>n<\/jats:italic>\u2009=\u20098, 80.0%), and difficulty engaging in play activities (<jats:italic>n<\/jats:italic>\u2009=\u20098, 80.0%).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The main finding from these patient interviews is the identification of six core signs\/symptoms of CHAPLE disease: abdominal pain, diarrhea, facial edema\/swelling, peripheral edema\/swelling, nausea, and vomiting. The severity of the core signs\/symptoms leads to substantial impacts on patients\u2019 lives.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>ClinicalTrials.gov, NCT04209634. Registered 20 December 2019 <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04209634\" ext-link-type=\"uri\">https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04209634<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-024-03436-y","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T16:11:34Z","timestamp":1739290294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The patient experience of CHAPLE disease: results from interviews conducted as part of a clinical trial for an ultra-rare condition"],"prefix":"10.1186","volume":"20","author":[{"given":"Leighann","family":"Litcher-Kelly","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"Ozen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Ollis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagit Baris","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Yaworsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Medrano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Voranush","family":"Chongsrisawat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorah","family":"Perlee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisa","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharanya","family":"Pradeep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane M.","family":"Turner-Bowker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Kurolap","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orly Eshach","family":"Adiv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Lenardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier A.","family":"Harari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-6466","authenticated-orcid":false,"given":"Jessica J.","family":"Jalbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"issue":"1","key":"3436_CR1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1056\/NEJMoa1615887","volume":"377","author":"A Ozen","year":"2017","unstructured":"Ozen A, Comrie WA, Ardy RC, Dom\u00ednguez Conde C, Dalgic B, Beser \u00d6, et al. CD55 Deficiency, early-onset protein-losing Enteropathy, and thrombosis. N Engl J Med. 2017;377(1):52\u201361.","journal-title":"N Engl J Med"},{"issue":"1","key":"3436_CR2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1056\/NEJMc1707173","volume":"377","author":"A Kurolap","year":"2017","unstructured":"Kurolap A, Eshach-Adiv O, Hershkovitz T, Paperna T, Mory A, Oz-Levi D, et al. Loss of CD55 in Eculizumab-Responsive protein-losing Enteropathy. N Engl J Med. 2017;377(1):87\u20139.","journal-title":"N Engl J Med"},{"key":"3436_CR3","unstructured":"Regeneron Pharmaceuticals. Pozelimab (C5 Antibody) BLA for Treatment of Children and Adults with Ultra-rare CHAPLE Disease Accepted for FDA Priority Review 02\/21\/2023 [05\/17\/2023]. https:\/\/investor.regeneron.com\/news-releases\/news-release-details\/pozelimab-c5-antibody-bla-treatment-children-and-adults-ultra"},{"issue":"3","key":"3436_CR4","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/MPG.0000000000002198","volume":"68","author":"A Kurolap","year":"2019","unstructured":"Kurolap A, Eshach Adiv O, Hershkovitz T, Tabib A, Karbian N, Paperna T, et al. Eculizumab is safe and effective as a long-term treatment for protein-losing Enteropathy due to CD55 Deficiency. 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Open-Label Efficacy and Safety Study of Pozelimab in Patients With CD55-Deficient Protein-Losing Enteropathy (CHAPLE Disease) 11\/10\/2022 [05\/17\/2023]. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04209634"},{"key":"3436_CR8","unstructured":"US Food and Drug Administration. FDA approves first treatment for CD55-deficient protein-losing enteropathy (CHAPLE disease) 2023 [cited 2023 9\/7\/2023]. https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-first-treatment-cd55-deficient-protein-losing-enteropathy-chaple-disease"},{"issue":"10427","key":"3436_CR9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/S0140-6736(23)02358-9","volume":"403","author":"A Ozen","year":"2024","unstructured":"Ozen A, Chongsrisawat V, Sefer AP, Kolukisa B, Jalbert JJ, Meagher KA, et al. Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study. Lancet (London England). 2024;403(10427):645\u201356.","journal-title":"Lancet (London England)"},{"key":"3436_CR10","volume-title":"Patient-focused Drug Development: collecting Comprehensive and Representative Input \u2013 Guidance for Industry, Food and Drug Administration Staff, and other stakeholders","author":"US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research","year":"2020","unstructured":"US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. 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The study protocol was approved by the local institutional review boards and\/or ethics committees prior to study initiation. All patients or their legally authorized representatives provided written informed consent prior to study enrollment. This study was conducted in accordance with the principles of the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines and was consistent with Good Clinical Practices of the International Conference on Harmonization and applicable regulatory requirements. Monitoring and site supervision were performed with oversight by the sponsor.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AO is a consultant and steering committee member for Regeneron, Pharmaceuticals, Inc.; received sample analysis support for a prior collaborative study () from Regeneron Pharmaceuticals, Inc.; and has a pending patent on C5 inhibitor treatment in CHAPLE disease. VC received support to conduct the study and provision of the investigational product from Regeneron Pharmaceuticals, Inc. JJJ, TB, and LP are Regeneron Pharmaceuticals, Inc. employees\/stockholders. OAH is an employee\/stockholder and has a pending patent on C5 inhibitor treatment in CHAPLE disease. MJL received support for a federally approved CRADA to support the clinical trial and has a pending patent on C5 inhibitor treatment in CHAPLE disease. LLK, SO, AY, PM, MW, and SP are employees of Adelphi Values who received sponsorship through Regeneron Pharmaceuticals, Inc. to conduct the study. DMTB was employed by Adelphi Values at the time this research was conducted though sponsorship by Regeneron Pharmaceuticals, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}