Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial

Gastroenterology. 2015 Jun;148(7):1311-9.e6. doi: 10.1053/j.gastro.2015.02.008. Epub 2015 Feb 13.

Abstract

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.

Keywords: Celiac Disease; Gluten; Therapeutic; Tight Junction.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Celiac Disease / complications
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy*
  • Celiac Disease / drug therapy*
  • Combined Modality Therapy
  • Diet, Gluten-Free*
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • North America
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • AT-1001
  • Gastrointestinal Agents
  • Oligopeptides

Associated data

  • ClinicalTrials.gov/NCT01396213