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

Aliment Pharmacol Ther. 2002 Mar;16(3):407-13. doi: 10.1046/j.1365-2036.2002.01194.x.


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 a 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 < or = 3. 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 < or = 3 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colitis, Ulcerative / drug therapy*
  • Female
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Male
  • Middle Aged
  • Pilot Projects
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / pharmacology
  • Serine Proteinase Inhibitors / therapeutic use*
  • Tryptases


  • Inflammation Mediators
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • Tryptases