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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: 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. Aim: To evaluate the efficacy and safety of BL-7040 (a Toll-like receptor-9 modulator) in patients with moderately active ulcerative colitis. Methods: 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. Results: 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. Conclusions: Oral administration of the Toll-like receptor-9 agonist BL-7040 appeared efficacious, safe and well tolerated in patients with moderately active ulcerative colitis.

Original languageEnglish
Pages (from-to)3246-3254
Number of pages9
JournalDigestive Diseases and Sciences
Volume61
Issue number11
DOIs
StatePublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Oral treatment
  • Pro-inflammatory cytokines
  • Synthetic oligonucleotide
  • Toll-like receptor-9
  • Ulcerative colitis

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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