TY - JOUR
T1 - Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge
AU - CeliacShield Study Group
AU - Murray, Joseph A.
AU - Syage, Jack A.
AU - Wu, Tsung Teh
AU - Dickason, Matthew A.
AU - Ramos, Ana G.
AU - Van Dyke, Carol
AU - Horwath, Irina
AU - Lavin, Philip T.
AU - Mäki, Markku
AU - Hujoel, Isabel
AU - Papadakis, Konstantinos A.
AU - Bledsoe, Adam C.
AU - Khosla, Chaitan
AU - Sealey-Voyksner, Jennifer A.
AU - Hinson, Chad
AU - Loskutov, Vasiliy
AU - Norum, Anna
AU - Linberg, Steven
AU - Goldkind, Lawrence
AU - Isola, Jorma
AU - Voyksner, Robert
AU - Luong, Pauline
AU - Baldwin, Matthew
AU - Nezzer, Jennifer
N1 - Publisher Copyright:
© 2022 AGA Institute
PY - 2022/12
Y1 - 2022/12
N2 - 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,
AB - 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,
KW - Inflammation
KW - Morphometry
KW - Treatment
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U2 - 10.1053/j.gastro.2022.07.071
DO - 10.1053/j.gastro.2022.07.071
M3 - Article
C2 - 35931103
AN - SCOPUS:85141968523
SN - 0016-5085
VL - 163
SP - 1510-1521.e6
JO - Gastroenterology
JF - Gastroenterology
IS - 6
ER -