{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:27:40Z","timestamp":1789576060114,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"IImmusanT, Inc, Cambridge, Massachusetts, USA"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nexvax2 contains three gluten\u2010derived peptides, intended to tolerize coeliac disease patients to gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen\u2010DQ2.5\u2010positive patients, most notably after an initial dose. Patients experience gastrointestinal symptoms with increases in serum interleukin\u20102. Consistent with Nexvax2\u2019s induction of non\u2010responsiveness, reactivity disappears after repeated doses, or is avoided with gradual dose escalation. Early clinical trials used intradermal dosing, but pharmacokinetics and rapid onset of effect suggest that subcutaneous delivery may also be effective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To document the relative bioavailability of Nevax2 peptides after subcutaneous and intradermal dosing, and the tolerability and ability of subcutaneous dosing to induce non\u2010responsiveness to Nexvax2 peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomised, double\u2010blind, placebo\u2010controlled study was conducted to assess plasma pharmacokinetics after subcutaneous and intradermal Nexvax2 dosing in HLA DQ2.5\u2010positive patients, who had symptoms after an oral gluten challenge. Randomisation was to semi\u2010weekly Nexvax2 (n\u00a0=\u00a012) or placebo (n\u00a0=\u00a02) injections, over a 5\u2010week subcutaneous dose escalation and 2\u2010week maintenance period, the latter with four doses of 900\u00a0\u00b5g, two subcutaneous and two intradermal. Post\u2010dose circulating peptide and interleukin\u20102 levels were assessed. Investigators recorded adverse events experienced by patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Subcutaneous dosing resulted in slightly greater exposure. Interleukin\u20102 responses were seen with the gluten challenge but not after subcutaneous or intradermal dosing of 900\u00a0\u00b5g. Adverse events were generally mild and self\u2010limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Subcutaneous and intradermal dosing of Nexvax2 yield similar bioavailability of constituent peptides; subcutaneous dose escalation avoids an immune response to dominant gluten epitopes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15435","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T09:43:59Z","timestamp":1565689439000},"page":"547-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Randomised clinical trial: a placebo\u2010controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-0212","authenticated-orcid":false,"given":"Kenneth E.","family":"Truitt","sequence":"first","affiliation":[{"name":"ImmusanT, Inc. 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