Efficacy & Safety in Moderately Active Refractory Ulcerative Colitis Patients

• Change in clinical remission rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Difference between clinical remission rate of subjects on KRP203 versus placebo
  
  

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Safety and tolerability of KRP203 assessed by the number of subjects with adverse events where KRP203 is given as an oral drug for 8 weeks once a day in ulcerative colitis subjects
  
  
• Pharmacokinetic properties of KRP203 at steady-state using whole blood samples in patients with ulcerative colitis subjects [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  
• Difference in pharmacokinetic levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To explore the relationship between KRP203 and KRP203-P pharmacokinetic levels and clinical efficacy outcomes such as the partial Mayo score and endoscopic modified Baron Score
  
  
• Assessment of the pharmacodynamic effect of KRP203 on absolute lymphocyte count and leukocyte subsets in ulcerative colitis subjects [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  
• Change in markers of inflammation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Measure of the effect of KRP203 on markers of inflammation, including but not limited to ESR, CRP and fecal calprotectin/ lactoferrin as well as histopathological markers of gut mucosa using biopsy samples in ulcerative colitis subjects
  
  

This is a multi-centre, double-blind, placebo controlled, parallel group, proof of concept study to evaluate the efficacy, safety and tolerability of KRP203 in subjects with moderately active refractory ulcerative colitis subjects. In total, approximately 72 subjects will be randomized into the study.

After 30 patients have completed the 8 week treatment period with KRP203 or placebo, there will be an interim analysis to determine preliminary efficacy. The study will consist of up to 28 day screening period (day -35 to -8), baseline period (day -7 to day -1), treatment period (day 1 to day 56), follow-up period and study completion.