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

CeliacShield Study Group; Joseph A Murray; Jack A Syage; Tsung-Teh Wu; Matthew A Dickason; Ana G Ramos; Carol Van Dyke; Irina Horwath; Philip T Lavin; Markku Mäki; Isabel Hujoel; Konstantinos A Papadakis; Adam C Bledsoe; Chaitan Khosla; Jennifer A Sealey-Voyksner

doi:10.1053/j.gastro.2022.07.071

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

CeliacShield Study Group, Joseph A Murray, Jack A Syage, Tsung-Teh Wu, Matthew A Dickason, Ana G Ramos, Carol Van Dyke, Irina Horwath, Philip T Lavin, Markku Mäki, Isabel Hujoel, Konstantinos A Papadakis, Adam C Bledsoe, Chaitan Khosla, Jennifer A Sealey-Voyksner

Research output: Contribution to journal › Article › Scientific › peer-review

32 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Gluten ingestion in celiac disease (CeD) patients can lead to gastrointestinal symptoms and small intestinal mucosal injury METHODS: This gluten-challenge (GC) Phase 2 trial was double-blind, placebo-controlled, and assessed the efficacy and safety of a 1,200 mg dose of IMGX003 in CeD patients exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth (Vh:Cd) was the primary endpoint. Secondary endpoints included densities of intraepithelial lymphocytes (IEL) and symptom severity. These endpoints were evaluated by ANCOVA. Additional endpoints included serology and gluten-immunogenic peptides (GIP) in urine RESULTS: Fifty (50) patients were randomized, and 43 patients completed (n=21 IMGX003, n=22 placebo). The mean ΔVh:Cd (primary endpoint) for IMGX003 vs. placebo was -0.04 vs. -0.35 (p = .057). The mean ΔIEL (secondary endpoint) for IMGX003 vs. placebo was 9.8 vs. 24.8 (p = .018). The mean change (worsening) in symptom severity (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 x 2-week trend-line significance for these symptoms, respectively, were p = .014, .030 and .002 CONCLUSION: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity.

CLINICALTRIALS: gov number NCT03585478.

Original language	English
Pages (from-to)	1510-1521.e6
Journal	Gastroenterology
Volume	163
Issue number	6
DOIs	https://doi.org/10.1053/j.gastro.2022.07.071
Publication status	Published - 2022
Publication type	A1 Journal article-refereed

Keywords

morphometry
inflammation
treatment

Publication forum classification

Publication forum level 3

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10.1053/j.gastro.2022.07.071

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CeliacShield Study Group, Murray, J. A., Syage, J. A., Wu, T.-T., Dickason, M. A., Ramos, A. G., Van Dyke, C., Horwath, I., Lavin, P. T., Mäki, M., Hujoel, I., Papadakis, K. A., Bledsoe, A. C., Khosla, C., & Sealey-Voyksner, J. A. (2022). Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients with Celiac Disease Exposed to a Gluten Challenge. Gastroenterology, 163(6), 1510-1521.e6. https://doi.org/10.1053/j.gastro.2022.07.071

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title = "Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients with Celiac Disease Exposed to a Gluten Challenge",

abstract = "BACKGROUND & AIMS: Gluten ingestion in celiac disease (CeD) patients can lead to gastrointestinal symptoms and small intestinal mucosal injury METHODS: This gluten-challenge (GC) Phase 2 trial was double-blind, placebo-controlled, and assessed the efficacy and safety of a 1,200 mg dose of IMGX003 in CeD patients exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth (Vh:Cd) was the primary endpoint. Secondary endpoints included densities of intraepithelial lymphocytes (IEL) and symptom severity. These endpoints were evaluated by ANCOVA. Additional endpoints included serology and gluten-immunogenic peptides (GIP) in urine RESULTS: Fifty (50) patients were randomized, and 43 patients completed (n=21 IMGX003, n=22 placebo). The mean ΔVh:Cd (primary endpoint) for IMGX003 vs. placebo was -0.04 vs. -0.35 (p = .057). The mean ΔIEL (secondary endpoint) for IMGX003 vs. placebo was 9.8 vs. 24.8 (p = .018). The mean change (worsening) in symptom severity (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 x 2-week trend-line significance for these symptoms, respectively, were p = .014, .030 and .002 CONCLUSION: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity.CLINICALTRIALS: gov number NCT03585478.",

keywords = "morphometry, inflammation, treatment",

author = "{CeliacShield Study Group} and Murray, {Joseph A} and Syage, {Jack A} and Tsung-Teh Wu and Dickason, {Matthew A} and Ramos, {Ana G} and {Van Dyke}, Carol and Irina Horwath and Lavin, {Philip T} and Markku M{\"a}ki and Isabel Hujoel and Papadakis, {Konstantinos A} and Bledsoe, {Adam C} and Chaitan Khosla and Sealey-Voyksner, {Jennifer A}",

year = "2022",

doi = "10.1053/j.gastro.2022.07.071",

language = "English",

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pages = "1510--1521.e6",

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publisher = "W.B. Saunders",

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CeliacShield Study Group, Murray, JA, Syage, JA, Wu, T-T, Dickason, MA, Ramos, AG, Van Dyke, C, Horwath, I, Lavin, PT, Mäki, M, Hujoel, I, Papadakis, KA, Bledsoe, AC, Khosla, C & Sealey-Voyksner, JA 2022, 'Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients with Celiac Disease Exposed to a Gluten Challenge', Gastroenterology, vol. 163, no. 6, pp. 1510-1521.e6. https://doi.org/10.1053/j.gastro.2022.07.071

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

PY - 2022

Y1 - 2022

N2 - BACKGROUND & AIMS: Gluten ingestion in celiac disease (CeD) patients can lead to gastrointestinal symptoms and small intestinal mucosal injury METHODS: This gluten-challenge (GC) Phase 2 trial was double-blind, placebo-controlled, and assessed the efficacy and safety of a 1,200 mg dose of IMGX003 in CeD patients exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth (Vh:Cd) was the primary endpoint. Secondary endpoints included densities of intraepithelial lymphocytes (IEL) and symptom severity. These endpoints were evaluated by ANCOVA. Additional endpoints included serology and gluten-immunogenic peptides (GIP) in urine RESULTS: Fifty (50) patients were randomized, and 43 patients completed (n=21 IMGX003, n=22 placebo). The mean ΔVh:Cd (primary endpoint) for IMGX003 vs. placebo was -0.04 vs. -0.35 (p = .057). The mean ΔIEL (secondary endpoint) for IMGX003 vs. placebo was 9.8 vs. 24.8 (p = .018). The mean change (worsening) in symptom severity (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 x 2-week trend-line significance for these symptoms, respectively, were p = .014, .030 and .002 CONCLUSION: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity.CLINICALTRIALS: gov number NCT03585478.

AB - BACKGROUND & AIMS: Gluten ingestion in celiac disease (CeD) patients can lead to gastrointestinal symptoms and small intestinal mucosal injury METHODS: This gluten-challenge (GC) Phase 2 trial was double-blind, placebo-controlled, and assessed the efficacy and safety of a 1,200 mg dose of IMGX003 in CeD patients exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth (Vh:Cd) was the primary endpoint. Secondary endpoints included densities of intraepithelial lymphocytes (IEL) and symptom severity. These endpoints were evaluated by ANCOVA. Additional endpoints included serology and gluten-immunogenic peptides (GIP) in urine RESULTS: Fifty (50) patients were randomized, and 43 patients completed (n=21 IMGX003, n=22 placebo). The mean ΔVh:Cd (primary endpoint) for IMGX003 vs. placebo was -0.04 vs. -0.35 (p = .057). The mean ΔIEL (secondary endpoint) for IMGX003 vs. placebo was 9.8 vs. 24.8 (p = .018). The mean change (worsening) in symptom severity (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 x 2-week trend-line significance for these symptoms, respectively, were p = .014, .030 and .002 CONCLUSION: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity.CLINICALTRIALS: gov number NCT03585478.

KW - morphometry

KW - inflammation

KW - treatment

U2 - 10.1053/j.gastro.2022.07.071

DO - 10.1053/j.gastro.2022.07.071

M3 - Article

C2 - 35931103

SN - 0016-5085

VL - 163

SP - 1510-1521.e6

JO - Gastroenterology

JF - Gastroenterology

IS - 6

ER -

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

Abstract

Keywords

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