{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:10:00Z","timestamp":1781518200442,"version":"3.54.1"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Akari Therapeutics"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To evaluate the safety and preliminary efficacy of topical rVA576, a dual inhibitor of complement component 5 (C5) and leukotriene B4 (LTB4), in patients with recalcitrant atopic keratoconjunctivitis (AKC) in the open label phase 1 TRACKER clinical trial.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Three patients diagnosed with moderate or severe AKC who had been on maximal topical treatment (antihistamines and ciclosporin) for at least three months prior to entry, and showed persistent symptoms and signs of inflammation, were recruited into the trial. Patients received rVA576 eye drops twice a day for 8\u00a0weeks. Patients were seen at baseline and weeks 1, 2, 4, 6 and 8. Safety data was recorded and a composite sum score of symptoms and signs was obtained. This score comprised symptoms such as itching, mucous discharge and photophobia, and conjunctival and corneal signs such as hyperemia, tarsal papillae, punctate keratitis and corneal neovascularization, all rated individually from 0 to 3 for a maximum score of 33.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Two of the three patients completed the initial open label phase of the trial. The third patient was unable to attend appointments and terminated the study early at day 14. Topical rVA576 was well tolerated with no serious adverse events reported. There was an average improvement in overall clinical score of 53%, composed of an improvement in symptoms of 65% [63.64\u201366.67%] and signs of 40% [40\u201340.12%] by day 56.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this open label phase 1 TRACKER trial, rVA576 eye drops were well tolerated and showed a response across signs and symptoms of active inflammation. This study is exploratory but supports topical rVA576 safety and shows promising efficacy for recalcitrant AKC. A phase 2 randomised control trial is currently underway.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-01890-6","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T13:02:50Z","timestamp":1623416570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dual inhibition of complement component 5 and leukotriene B4 by topical rVA576 in atopic keratoconjunctivis: TRACKER phase 1 clinical trial results"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-2890","authenticated-orcid":false,"given":"Sara","family":"S\u00e1nchez-Tabernero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Fajardo-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wynne","family":"Weston-Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Kriman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"issue":"4","key":"1890_CR1","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.4049\/jimmunol.174.4.2084","volume":"174","author":"MA Nunn","year":"2005","unstructured":"Nunn MA, Sharma A, Paesen GC, Adamson S, Lissina O, Willis AC, Nuttall PA. Complement inhibitor of C5 activation from the soft tick Ornithodoros moubata. J Immunol. 2005;174(4):2084\u201391. https:\/\/doi.org\/10.4049\/jimmunol.174.4.2084.","journal-title":"J Immunol"},{"issue":"10","key":"1890_CR2","first-page":"1945","volume":"31","author":"BJ Mondino","year":"1990","unstructured":"Mondino BJ, Sumner HL. Generation of complement-derived anaphylatoxins in normal human donor corneas. Investig Ophthalmol Vis Sci. 1990;31(10):1945\u20139.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1890_CR3","doi-asserted-by":"publisher","first-page":"247e57","DOI":"10.1007\/bf01664932","volume":"85","author":"H Nathan","year":"1994","unstructured":"Nathan H, Naveh N, Meyer E. Levels of prostaglandin E2 and leukotriene B4 in tears of vernal conjunctivitis patients during a therapeutic trial with indomethacin. 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Ophthalmology. 2004;111(3):476\u201382. https:\/\/doi.org\/10.1016\/j.ophtha.2003.05.035.","journal-title":"Ophthalmology"},{"key":"1890_CR6","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16305","author":"S Schols","year":"2019","unstructured":"Schols S, Nunn MA, Mackie I, Weston-Davies W, Nishimura JI, Kanakura Y, Blijlevens N, Muus P, Langemeijer S. Successful treatment of a PNH patient non-responsive to eculizumab with the novel complement C5 inhibitor coversin (nomacopan). Br J Haematol. 2019. https:\/\/doi.org\/10.1111\/bjh.16305.","journal-title":"Br J Haematol"},{"issue":"5","key":"1890_CR7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/nsmb.3196","volume":"23","author":"MM Jore","year":"2016","unstructured":"Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, Elmlund H, Lea SM. Structural basis for therapeutic inhibition of complement C5. 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Informed consent for experimentation with human subjects was obtained from the patients prior to entering the trial.","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":"Mr. Wynne Weston-Davies works for Akari Therapeutics as Medical Director. The remaining authors declare they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"270"}}