IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis

Copyright © 2016 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 174(2017) vom: 01. Jan., Seite 63-72
1. Verfasser: Balak, Deepak M W (VerfasserIn)
Weitere Verfasser: van Doorn, Martijn B A, Arbeit, Robert D, Rijneveld, Rianne, Klaassen, Erica, Sullivan, Tim, Brevard, Julie, Thio, Hok Bing, Prens, Errol P, Burggraaf, Jacobus, Rissmann, Robert
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Drug-development Endosomal toll-like receptors Human beta-defensin-2 Immune-mediated inflammatory diseases Oligonucleotide antagonist Type 1 interferon signaling pathway mehr... DEFB4A protein, human TLR7 protein, human TLR8 protein, human TLR9 protein, human Toll-Like Receptor 7 Toll-Like Receptor 8 Toll-Like Receptor 9 beta-Defensins
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100 1 |a Balak, Deepak M W  |e verfasserin  |4 aut 
245 1 0 |a IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis 
264 1 |c 2017 
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500 |a Date Completed 13.06.2017 
500 |a Date Revised 06.02.2018 
500 |a published: Print-Electronic 
500 |a ClinicalTrials.gov: NCT01899729 
500 |a EudraCT: 2013-000164-28 
500 |a Citation Status MEDLINE 
520 |a Copyright © 2016 Elsevier Inc. All rights reserved. 
520 |a BACKGROUND: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial 
520 |a METHODS: Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI) 
520 |a RESULTS: IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo 
520 |a CONCLUSIONS: Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs 
520 |a TRIAL REGISTRATION: EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729 
650 4 |a Clinical Trial, Phase II 
650 4 |a Journal Article 
650 4 |a Randomized Controlled Trial 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Drug-development 
650 4 |a Endosomal toll-like receptors 
650 4 |a Human beta-defensin-2 
650 4 |a Immune-mediated inflammatory diseases 
650 4 |a Oligonucleotide antagonist 
650 4 |a Type 1 interferon signaling pathway 
650 7 |a DEFB4A protein, human  |2 NLM 
650 7 |a TLR7 protein, human  |2 NLM 
650 7 |a TLR8 protein, human  |2 NLM 
650 7 |a TLR9 protein, human  |2 NLM 
650 7 |a Toll-Like Receptor 7  |2 NLM 
650 7 |a Toll-Like Receptor 8  |2 NLM 
650 7 |a Toll-Like Receptor 9  |2 NLM 
650 7 |a beta-Defensins  |2 NLM 
700 1 |a van Doorn, Martijn B A  |e verfasserin  |4 aut 
700 1 |a Arbeit, Robert D  |e verfasserin  |4 aut 
700 1 |a Rijneveld, Rianne  |e verfasserin  |4 aut 
700 1 |a Klaassen, Erica  |e verfasserin  |4 aut 
700 1 |a Sullivan, Tim  |e verfasserin  |4 aut 
700 1 |a Brevard, Julie  |e verfasserin  |4 aut 
700 1 |a Thio, Hok Bing  |e verfasserin  |4 aut 
700 1 |a Prens, Errol P  |e verfasserin  |4 aut 
700 1 |a Burggraaf, Jacobus  |e verfasserin  |4 aut 
700 1 |a Rissmann, Robert  |e verfasserin  |4 aut 
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856 4 0 |u http://dx.doi.org/10.1016/j.clim.2016.09.015  |3 Volltext 
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