title: Ameliorating Active Ulcerative Colitis via an Orally Available Toll-Like Receptor-9 Modifier: A Prospective Open-Label, Multicenter Phase II Trial.
abstract: Treatment 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.
  
  
  
  To evaluate the efficacy and safety of BL-7040 (a Toll-like receptor-9 modulator) in patients with moderately active ulcerative colitis.
  
  
  
  Moderately 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.
  
  
  
  Sixteen 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.
  
  
  
  Oral administration of the Toll-like receptor-9 agonist BL-7040 appeared efficacious, safe and well tolerated in patients with moderately active ulcerative colitis.
authors: Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv, Israel. irisd@tlvmc.gov.il.
authors: Iris
authors: I
authors: Dotan
authors: BioLineRx Ltd., Modi'in, Israel.
authors: Etgar
authors: E
authors: Levy-Nissenbaum
authors: Department of Gastroenterology, Rambam Health Care Campus, Bat Galim, Haifa, Israel.
authors: Yehuda
authors: Y
authors: Chowers
authors: Department of Gastroenterology, Soroka Medical Center, Beer Sheba, Israel.
authors: Alexander
authors: A
authors: Fich
authors: IBD Unit, Institute of Gastroenterology and Liver Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Eran
authors: E
authors: Israeli
authors: Digestive Diseases Institute, Shaare Zedek Medical Center Affiliated with The Hebrew University, Jerusalem, Israel.
authors: Tomer
authors: T
authors: Adar
authors: Digestive Diseases Institute, Shaare Zedek Medical Center Affiliated with The Hebrew University, Jerusalem, Israel.
authors: Shimon
authors: S
authors: Shteingart
authors: Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors: Hermona
authors: H
authors: Soreq
authors: Digestive Diseases Institute, Shaare Zedek Medical Center Affiliated with The Hebrew University, Jerusalem, Israel.
authors: Eran
authors: E
authors: Goldin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; C477243:EN101; C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; C439524:TNF protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12
keywords: Oral treatment; Pro-inflammatory cytokines; Synthetic oligonucleotide; Toll-like receptor-9; Ulcerative colitis