Randomised clinical trial: a placebo‐controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease

摘要: Background Nexvax2 contains three gluten-derived peptides, intended to tolerize coeliac disease patients gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen-DQ2.5-positive patients, most notably after an initial dose. Patients experience gastrointestinal symptoms with increases serum interleukin-2. Consistent Nexvax2's induction of non-responsiveness, reactivity disappears repeated doses, or is avoided gradual dose escalation. Early clinical trials used intradermal dosing, but pharmacokinetics and rapid onset effect suggest subcutaneous delivery may also be effective. Aims To document the relative bioavailability Nevax2 peptides tolerability ability dosing induce non-responsiveness peptides. Methods A randomised, double-blind, placebo-controlled study was conducted assess plasma HLA DQ2.5-positive who had oral gluten challenge. Randomisation semi-weekly (n = 12) placebo 2) injections, over a 5-week escalation 2-week maintenance period, latter four doses 900 mu g, two intradermal. Post-dose circulating peptide interleukin-2 levels were assessed. Investigators recorded adverse events experienced by patients. Results Subcutaneous resulted slightly greater exposure. Interleukin-2 responses seen challenge not g. Adverse generally mild self-limited. Conclusions yield similar constituent peptides; avoids response dominant epitopes.