An Open-Label Study to Evaluate the Efficacy, Pharmacodynamics, Safety and Tolerability of Oral BL-7040 in Patients With Moderately Active Ulcerative Colitis

The objective of the proposed study is to determine whether BL-7040 demonstrates clinical efficacy in patients with inflammatory bowel disease (IBD).

开始日期2012-03-01

申办/合作机构

BioLineRx Ltd.

100 项与 BL-7040 相关的临床结果

登录后查看更多信息

100 项与 BL-7040 相关的转化医学

登录后查看更多信息

100 项与 BL-7040 相关的专利（医药）

登录后查看更多信息

项与 BL-7040 相关的文献（医药）

2018-08-01·BioDrugs3区 · 医学

Oligonucleotide-Based Therapies for Inflammatory Bowel Disease

3区 · 医学

Review

作者: Marafini, Irene ; Bevivino, Gerolamo ; Monteleone, Giovanni ; Sedda, Silvia

The growing understanding of the immunopathogenesis of inflammatory bowel diseases (IBDs) has contributed to the identification of new targets whose expression/activity can be modulated for therapeutic purposes. Several approaches have been employed to develop selective pharmaceutical compounds; among these, antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid option for inhibiting or enhancing, respectively, the expression/function of molecules that have been implicated in the control of IBD-related inflammation. In this context, data have been accumulated for the following compounds: alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane glycoprotein that regulates rolling and adhesion of leukocytes to inflamed intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance Toll-like receptor-9 activity; Mongersen, an ASO that inhibits Smad7, thereby restoring transforming growth factor-β1/Smad-associated signaling; STNM01, a double-stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting expression of the transcription factor GATA3. In this article, we review the rationale and the available data relative to the use of these agents in IBD. Although pre-clinical and phase II trials in IBD support the use of oligonucleotide-based therapies for treating the pathogenic process occurring in the gut of patients with these disorders, further work is needed to establish whether and which patients can benefit from specific ASOs and identify biomarkers that could help optimize treatment.

2016-11-01·Digestive Diseases and Sciences3区 · 医学

Ameliorating Active Ulcerative Colitis via an Orally Available Toll-Like Receptor-9 Modifier: A Prospective Open-Label, Multicenter Phase II Trial

3区 · 医学

Article

作者: Adar, Tomer ; Fich, Alexander ; Chowers, Yehuda ; Dotan, Iris ; Levy-Nissenbaum, Etgar ; Goldin, Eran ; Soreq, Hermona ; Israeli, Eran ; Shteingart, Shimon

BACKGROUNDTreatment of active ulcerative colitis is associated with incomplete efficacy, adverse events, and loss of response. Toll-like receptor-9 mediates innate and adaptive immune response toward intestinal microorganisms. The oral synthetic oligonucleotide toll-like receptor-9 modulator has demonstrated anti-inflammatory properties in colitis murine models and a satisfactory safety profile in humans.AIMTo evaluate the efficacy and safety of BL-7040 (a Toll-like receptor-9 modulator) in patients with moderately active ulcerative colitis.METHODSModerately active ulcerative colitis patients were included in this multicenter, open-label phase IIa trial. Concomitant mesalamine and steroids at a stable dose were allowed. Clinical outcome was evaluated using the Mayo score, histology, and mucosal cytokine levels. Side effects were registered.RESULTSSixteen out of 22 patients completed a 5-week treatment course and 2-week follow-up. Six patients discontinued the study, three of them due to adverse events. Clinical remission was observed in two patients (12.5 %), and clinical response as well as mucosal healing were achieved in half (50 %) of the patients, while all others remained stable. Furthermore, mucosal neutrophil (p = 0.002) and mucosal interleukin-6 levels (p = 0.046) were significantly reduced in responders compared to non-responders. Toll-like receptor-9 was well tolerated with only one unrelated to study drug serious adverse event (hemoglobin decrease) and 29 mild-to-moderate adverse events.CONCLUSIONSOral administration of the Toll-like receptor-9 agonist BL-7040 appeared efficacious, safe and well tolerated in patients with moderately active ulcerative colitis.

2015-11-01·International Immunopharmacology2区 · 医学

Gut feeling: MicroRNA discriminators of the intestinal TLR9–cholinergic links

2区 · 医学

Article

作者: Nadorp, Bettina ; Soreq, Hermona

The intestinal tissue notably responds to stressful, cholinergic and innate immune signals by microRNA (miRNA) changes, but whether and how those miRNA regulators modify the intestinal cholinergic and innate immune pathways remained unexplored. Here, we report changes in several miRNA regulators of cholinesterases (ChEs) and correspondingly modified ChE activities in intestine, splenocytes and the circulation of mice exposed to both stress and canonical or alternative Toll-Like Receptor 9 (TLR9) oligonucleotide (ODN) aptamer activators or blockers. Stressful intraperitoneal injection of saline, the anti-inflammatory TLR9 agonist mEN101 aptamer or the inflammation-activating TLR9 aptamer ODN 1826 all increased the expression of the acetylcholinesterase (AChE)-targeting miR-132. In comparison, mEN101 but neither ODN 1826 nor saline injections elevated intestinal miR-129-5p, miR-186 and miR-200c, all predicted to target both AChE and the homologous enzyme butyrylcholinesterase (BChE). In cultured immune cells, BL-7040, the human counterpart of mEN101, reduced AChE activity reflecting inflammatory reactions in a manner preventable by the TLR9 blocking ODN 2088. Furthermore, the anti-inflammatory BL-7040 TLR9 aptamer caused reduction in nitric oxide and AChE activity in both murine splenocytes and human mononuclear cells at molar concentrations four orders of magnitude lower than ODN 1826. Our findings demonstrate differential reaction of cholinesterase-targeting miRNAs to distinct TLR9 challenges, indicating upstream miRNA co-regulation of the intestinal alternative NFκB pathway and cholinergic signaling. TLR9 aptamers may hence potentiate miRNA regulation that enhances cholinergic signaling and the resolution of inflammation, which opens new venues for manipulating bowel diseases.

100 项与 BL-7040 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床2期	以色列	BioLineRx Ltd.	2012-03-01
多发性硬化症	临床2期	美国	Amarin Corp. Plc	-
重症肌无力	临床2期	以色列	Ester Neurosciences Ltd.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01506362 (Pubmed \| Dig Dis Sci) 人工标引	临床2期	溃疡性结肠炎	22	BL-7040	(積鏇鑰遞廠構壓築繭鑰) = 夢製觸觸衊選餘觸鏇淵廠襯選憲繭製襯積積繭 (構鹽淵齋網鏇繭選鹽選 ) 更多	积极	2016-11-01
NCT01506362 (CTgov)	临床2期	溃疡性结肠炎	22	BL-7040	蓋選構築築膚鏇遞衊衊(鏇壓鏇鏇壓鑰窪製餘壓) = 醖淵膚繭淵膚艱蓋顧夢齋繭夢醖簾鏇願艱淵壓 (觸鹹遞廠範襯簾願淵膚, 衊醖餘醖鹽膚衊網構範 ~ 構醖願繭壓壓憲憲繭窪) 更多	-	2014-05-01