Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge

Abstract

Background & 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 endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine.

Results: Fifty 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 endpoint) for IMGX003 vs placebo was -0.04 vs -0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P = .231), 0.96 vs 3.29 (bloating, P = .204), and 0.02 vs 3.20 (tiredness, P = .113). The 3 × 2-week trend line significance values for these symptoms, respectively, were P = .014, .030, and .002.

Conclusions: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. (ClinicalTrials.gov, Number: NCT03585478).

Keywords: Inflammation; Morphometry; Treatment.

Figure 1.

IMGX003-NCCIH-1721 CeliacShield study (A) schematic and (B) enrollment flow chart.

Figure 2.

Symptom results for abdominal pain, bloating, tiredness, and non-stool composite which includes these symptoms and nausea. (A) Absolute severity for baseline and the 6-week GC treatment period for IMGX003 vs. placebo groups. Also shown are the magnitude of worsening for baseline vs. 6-week GC period. P-values are by ANCOVA for inter-group and paired t-test for intra-group results. (B) Mean change from baseline (% worsening) for three 2-week sequential GC treatment periods for IMGX003 vs. placebo. Also shown are the unpaired, 2-tailed, t-test p-values.

Figure 3.

(A) Mean gluten immunogenic peptide (GIP) concentration in urine before (V3), during (6 weekly readings) and after (V4) the GC treatment period with unpaired, 2-tailed, t-test p-value. (B) Subject responses for GIP concentration in urine showing individual subject changes. (C) Box and whisker plot showing min and max, 1^st and 3^rd quartile and median and ANCOVA p-value.