en101 and Colitis--Ulcerative

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.

Topics: Administration, Oral; Adult; Colitis, Ulcerative; Colon; Female; Humans; Interleukin-10; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Neutrophils; Oligodeoxyribonucleotides; Toll-Like Receptor 9; Treatment Outcome; Tumor Necrosis Factor-alpha