Esophagus to Small Intestine
Latiglutenase protects the mucosa and attenuates symptom severity in patients with celiac disease exposed to a gluten challenge
Background and aims: Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury.
Methods: This gluten challenge phase 2 trial was double-blind and placebo-controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary end point. Secondary end points included density of intraepithelial lymphocytes and symptom severity. These end points were evaluated by analysis of covariance. Additional end points included serology and gluten-immunogenic peptides in urine.
Results: 50 patients were randomized, and 43 patients completed the study (IMGX003, n = 21; placebo, n = 22). The mean change in the ratio of villus height to crypt depth (primary end point) for IMGX003 versus placebo was -0.04 versus -0.35 (p = 0.057). The mean change in the density of intraepithelial lymphocytes (secondary end point) for IMGX003 versus placebo was 9.8 versus 24.8 cells/mm epithelium (p = 0.018). The mean change (worsening) in symptom severity in relative units (secondary end point) for IMGX003 versus placebo was 0.22 versus 1.63 (abdominal pain, p = 0.231), 0.96 versus 3.29 (bloating, p = 0.204), and 0.02 versus 3.20 (tiredness, p = 0.113). The 3 x 2-week trend line significance values for these symptoms, respectively, were p = 0.014, 0.030, and 0.002.
Conclusions: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity.