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

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Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge
Gastroenterology ( IF 25.7 ) Pub Date : 2022-08-02 , DOI: 10.1053/j.gastro.2022.07.071
Joseph A Murray ₁ , Jack A Syage ₂ , Tsung-Teh Wu ₃ , Matthew A Dickason ₂ , Ana G Ramos ₂ , Carol Van Dyke ₁ , Irina Horwath ₁ , Philip T Lavin ₄ , Markku Mäki ₅ , Isabel Hujoel ₁ , Konstantinos A Papadakis ₃ , Adam C Bledsoe ₁ , Chaitan Khosla ₆ , Jennifer A Sealey-Voyksner ₂ ,

Affiliation

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)

中文翻译：

Latiglutenase 可保护接受麸质挑战的乳糜泻患者的粘膜并减轻症状严重程度

背景与目标

乳糜泻患者摄入麸质会导致胃肠道症状和小肠粘膜损伤。

方法

这项麸质挑战 2 期试验是双盲和安慰剂对照的，它评估了 1200 毫克剂量的 IMGX003 对于每天接触 2 g 麸质、持续 6 周的乳糜泻患者的有效性和安全性。绒毛高度与隐窝深度之比的变化是主要终点。次要终点包括上皮内淋巴细胞密度和症状严重程度。通过协方差分析来评估这些终点。其他终点包括血清学和尿液中的麸质免疫原性肽。

结果

50 名患者被随机分配，43 名患者完成了研究（IMGX003，n = 21；安慰剂，n = 22）。 IMGX003 与安慰剂相比，绒毛高度与隐窝深度之比（主要终点）的平均变化分别为 –0.04 与 –0.35 ( P = .057)。 IMGX003 与安慰剂相比，上皮内淋巴细胞密度的平均变化（次要终点）分别为 9.8 个细胞/mm 上皮和 24.8 个细胞/mm 上皮 ( P = .018)。 IMGX003 与安慰剂相比，相对单位（次要终点）症状严重程度的平均变化（恶化）分别为 0.22 vs 1.63（腹痛， P = 0.231）、0.96 vs 3.29（腹胀， P = 0.204）和 0.02 vs 3.20 （疲劳， P = .113）。这些症状的 3 × 2 周趋势线显着性值分别为P = .014、.030 和 .002。