Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 148; no. 7; pp. 1311 - 1319.e6
• Main Authors: Leffler, Daniel A, Kelly, Ciaran P, Green, Peter H.R, Fedorak, Richard N, DiMarino, Anthony, Perrow, Wendy, Rasmussen, Henrik, Wang, Chao, Bercik, Premysl, Bachir, Natalie M, Murray, Joseph A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2015
• Subjects: Adult; Celiac Disease; Celiac Disease - complications; Celiac Disease - diagnosis; Celiac Disease - diet therapy; Celiac Disease - drug therapy; Combined Modality Therapy; Diet, Gluten-Free; Double-Blind Method; Female; Gastroenterology and Hepatology; Gastrointestinal Agents - adverse effects; Gastrointestinal Agents - therapeutic use; Gluten; Humans; Male; Middle Aged; North America; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Therapeutic; Tight Junction; Time Factors; Treatment Outcome; North America; GI; CeD; GFD; gluten-free diet; body mass index; tTG; CeD PRO; Therapeutic; Celiac Disease Patient-Reported Outcome; DGP; tissue transglutaminase; mixed model for repeated measures; gastrointestinal; ANCOVA; CeD-GSRS; Celiac Disease Gastrointestinal Symptom Rating Scale; TJ; Celiac Disease; Gluten; analysis of covariance; deamidated gliadin peptide; Tight Junction; BMI; MMRM
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2015.02.008

Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P  = .022; mixed model for repeated measures, P  = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P  = .017), a 31% increase in improved symptom days ( P  = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P  = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P  = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov : NCT01396213.