Beyond the gluten-free diet: Innovations in celiac disease therapeutics

Table 4 Phase 2 studies exploring lymphocyte trafficking and homing inhibitors

NCT number	Study title	Study status (Completion date)	Drug	Mechanism	Primary outcome measures	Sponsor	Phases
NCT00540657	A Phase 2 study of CCX282-B in patients with CD	Completed (July 2008)	CCX282 vs placebo	CCX282-B is a chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine	Evaluation of the effect of CCX282-B compared to placebo on the Vh:Cd ratio of small intestinal biopsy specimens taken from patients with CD, before and after gluten exposure	ChemoCentryx	Phase 2
NCT02929316	Vedolizumab induction may prevent celiac enteritis	Terminated (October 5, 2018)	Vedolizumab	Vedolizumab is a monoclonal antibody against integrin α4β7 that inhibit lymphocyte homing to the bowel	Histopathologic remission following induction with vedolizumab (defined as negative CD antibodies and normal duodenal biopsies) at 12 weeks	AGA Clinical Research Associates, LLC	Phase 2
NCT04806737	A Phase 2a, double-blind, randomized, placebo-controlled study on the efficacy and tolerability of a 14-day treatment with teriflunomide vs placebo in subjects with coeliac disease undergoing a 3-day gluten challenge	Unknown (August 15, 2022)	Oral teriflunomide vs placebo	Teriflunomide inhibits de novo synthesis of pyrimidine, performing a cytostatic effect on lymphocyte proliferation	Check the adaptive T-cell activation, evaluating the expression of CD38 on HLA-DQ: Gluten tetramer-positive T cells on peripheral blood on day 4 after a 3-day gluten challenge	Oslo University Hospital	Phase 1-phase 2
NCT02637141	A Phase 2a, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of AMG 714 in adult patients with CD	Completed (May 2, 2017)	AMG 714 vs placebo	AMG 714 is a monoclonal antibody an anti-IL-15, a pivotal cytokine in CD pathogenesis	Percent change from baseline in Vh:CD. To evaluate the attenuation of the effects of gluten exposure after 10 weeks of gluten challenge at week 12	Amgen	Phase 2
NCT02633020	A Phase 2a, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of AMG 714 in adult patients with type II refractory CD	Completed (May 2, 2017)	AMG 714 vs placebo	AMG 714 is a monoclonal antibody anti-IL-15	Percent change from baseline in the percentage of aberrant intestinal intraepithelial lymphocytes with respect to all intraepithelial lymphocytes at baseline and week 12	Amgen	Phase 2
NCT04424927 proactive	A Phase 2b, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of PRV-015 in adult patients with non-responsive CD as an adjunct to a gluten-free diet	Recruiting (August 31, 2024)	PRV-015 vs placebo	PRV-015 is a monoclonal antibody against IL-15, a pivotal cytokine in CD pathogenesis	Efficacy of PRV-015 in attenuating the symptoms of CD in non-responsive CD as measured by the celiac disease patient-reported outcome questionnaire at 24 weeks	Provention Bio, Inc.	Phase 2
NCT05636293	Double-blind, placebo-controlled trial to establish safety and efficacy of ritlecitinib to prevent gluten-induced celiac enteropathy and symptoms in CD patients in remission	Recruiting (January 1, 2025)	Ritlecitinib vs placebo	Ritlecitinib is a selective Janus kinase 3 inhibitors that prevent lymphocyte activation and proliferation	Change in small intestinal histology based on Vh:Cd ratio to characterize the gluten-challenge induced changes. Patient-reported outcomes defined as CD PRO to evaluate gluten challenge-triggered symptoms. Through study completion, average of 1 year	Massachusetts General Hospital	Phase 2

CD: Celiac disease; CCR9: C-C chemokine receptor type 9; IL: Interleukin; PROs: Patient-reported outcomes; Vh:Cd: Villous height to crypt depth ratio.