Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients : A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial
© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
|---|---|
| Enthalten in: |
Journal of Crohn's & colitis - 18(2024), 3 vom: 01. März, Seite 406-415 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Atreya, Raja [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
63231-63-0 |
|---|
| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/ecco-jcc/jjad162 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM362731349 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM362731349 | ||
| 003 | DE-627 | ||
| 005 | 20240304231951.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/ecco-jcc/jjad162 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1316.xml |
| 035 | |a (DE-627)NLM362731349 | ||
| 035 | |a (NLM)37777210 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Atreya, Raja |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients |b A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.03.2024 | ||
| 500 | |a Date Revised 04.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a 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] | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CHST15 | |
| 650 | 4 | |a GUT-1 | |
| 650 | 4 | |a RNA oligonucleotide | |
| 650 | 4 | |a Ulcerative colitis | |
| 650 | 4 | |a fibrosis | |
| 650 | 4 | |a submucosal injection | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a Oligonucleotides |2 NLM | |
| 700 | 1 | |a Kühbacher, Tanja |e verfasserin |4 aut | |
| 700 | 1 | |a Waldner, Maximilian J |e verfasserin |4 aut | |
| 700 | 1 | |a Hirschmann, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Drvarov, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Abu Hashem, Raed |e verfasserin |4 aut | |
| 700 | 1 | |a Maaser, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Kucharzik, Torsten |e verfasserin |4 aut | |
| 700 | 1 | |a Dinter, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Mertens, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Schramm, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Holler, Babett |e verfasserin |4 aut | |
| 700 | 1 | |a Mössner, Joachim |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Yokoyama, Junji |e verfasserin |4 aut | |
| 700 | 1 | |a Terai, Shuji |e verfasserin |4 aut | |
| 700 | 1 | |a Uter, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Yoneyama, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Asakura, Hitoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Hibi, Toshifumi |e verfasserin |4 aut | |
| 700 | 1 | |a Neurath, Markus F |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of Crohn's & colitis |d 2007 |g 18(2024), 3 vom: 01. März, Seite 406-415 |w (DE-627)NLM204021901 |x 1876-4479 |7 nnns |
| 773 | 1 | 8 | |g volume:18 |g year:2024 |g number:3 |g day:01 |g month:03 |g pages:406-415 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/ecco-jcc/jjad162 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 18 |j 2024 |e 3 |b 01 |c 03 |h 406-415 | ||