Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study

Background: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. Aim: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. Methods: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with it disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of less than or equal to3. Supplementary analyses were also performed. Results: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index = 0). Twenty-seven (49%) improved, with a final disease activity index of less than or equal to3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%: bleeding. 64%: endoscopy, 50%: physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). Conclusions: in this pilot study, the tryptase inhibitor APC 2059,was safe and there was evidence of activity in the treatment of ulcerative colitis.