Epitope-Specific Immunotherapy Targeting CD4-Positive T Cells in Celiac Disease: Safety, Pharmacokinetics, and Effects on Intestinal Histology and Plasma Cytokines with Escalating Dose Regimens of Nexvax2 in a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study.

Background: Nexvax2® is a novel, peptide-based, epitope-specific immunotherapy intended to be administered by regular injections at dose levels that increase the threshold for clinical reactivity to natural exposure to gluten and ultimately restore tolerance to gluten in patients with celiac disease. Celiac disease patients administered fixed intradermal doses of Nexvax2 become unresponsive to the HLA-DQ2·5-restricted gluten epitopes in Nexvax2, but gastrointestinal symptoms and cytokine release mimicking gluten exposure, that accompany the first dose, limit the maximum tolerated dose to 150μg. Our aim was to test whether stepwise dose escalation attenuated the first dose effect of Nexvax2 in celiac disease patients.