Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial.

Atreya R, Kühbacher T, Waldner M, Hirschmann S, Drvarov O, Abu Hashem R, Maaser C, Kucharzik T, Dinter J, Mertens J, Schramm C, Holler B, Mössner J, Suzuki K, Yokoyama J, Terai S, Uter W, Yoneyama H, Asakura H, Hibi T, Neurath M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 18

Pages Range: 406-415

Journal Issue: 3

DOI: 10.1093/ecco-jcc/jjad162

Abstract

BACKGROUND AND AIMS: Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC]. METHODS: In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment. RESULTS: Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated. CONCLUSION: Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC.

Authors with CRIS profile

Involved external institutions

Asklepios Kliniken Germany (DE) Städtisches Klinikum Lüneburg Germany (DE) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Köln Germany (DE) Kitasato University / 北里大学 (Kitasato Daigaku) Japan (JP) Niigata University Medical & Dental Hospital Japan (JP) Gut Inc. Japan (JP)

How to cite

APA:

Atreya, R., Kühbacher, T., Waldner, M., Hirschmann, S., Drvarov, O., Abu Hashem, R.,... Neurath, M. (2024). Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial. Journal of Crohns & Colitis, 18(3), 406-415. https://doi.org/10.1093/ecco-jcc/jjad162

MLA:

Atreya, Raja, et al. "Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial." Journal of Crohns & Colitis 18.3 (2024): 406-415.

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