Efficacy & Safety in Moderately Active Refractory Ulcerative Colitis Patients

Study Overview
=================
Brief Summary
-----------------
This study is designed as a proof of concept of KRP203 for induction of remission in ulcerative colitis (UC). The purpose of this study is to evaluate clinical benefit of KRP203 in subjects with moderately active refractory ulcerative colitis. The study will provide safety and tolerability data in this subject population up to eight weeks of treatment with KRP203. Additionally, this study will evaluate the duration of a clinical response to KRP203 by following up responding subjects for an additional 12 weeks.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: KRP203
* Drug: Placebo matching KRP203


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Active disease defined by partial Mayo score and modified Baron score with disease extending at least 25 cm from the anal verge Subjects must have inadequately responded or intolerance to 5-ASA therapy Exclusion Criteria: Subjects receiving treatment for UC (other than 5-ASAs and steroids) within the time frame mentioned in protocol Past or recent history of significant medical illness and/or clinically significant lab abnormalities including but not limited to hematology, clinical chemistry, urine analysis, ECG abnormalities, HIV, Hepatitis B/C Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, ophthalmic, cardiac, blood, renal, hepatic, infectious, psychiatric or any medically unstable condition, as assessed by the primary treating physician which, in the opinion of the investigator, would immunocompromise the subject and/or place the subject at unacceptable risk for participation in a study of an immunomodulatory therapy Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KRP203<br>Experimental Edit Experimental | Drug: KRP203<br> <br> |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo matching KRP203<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical remission rate | Difference between clinical remission rate of subjects on KRP203 versus placebo | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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 | 8 weeks | 
| Pharmacokinetic properties of KRP203 at steady-state using whole blood samples in patients with ulcerative colitis subjects |  | 8 weeks | 
| Difference in pharmacokinetic levels | 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 | 12 weeks | 
| Assessment of the pharmacodynamic effect of KRP203 on absolute lymphocyte count and leukocyte subsets in ulcerative colitis subjects |  | 12 weeks | 
| Change in markers of inflammation | 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 | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammatory Bowel disease, Ulcerative colitis