A Study To Evaluate Both The Efficacy and Safety Profile of CP-690,550 In Patients With Moderately to Severely Active Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the efficacy and safety of tofacitinib (CP-690,550) in patients with moderate to severe ulcerative colitis who have failed or be intolerant to one of following treatments for ulcerative colitis: oral steroids, azathiopurine/6-mercaptopurine, or anti-TNF-alpha therapy.

Official Title
-----------------
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis.

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

Intervention / Treatment
-----------------
* Drug: tofacitinib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must be at least 18 years of age. Males and females with a documented diagnosis of UC at least 4 months prior to entry into the study. Subjects with moderately to severely active UC based on Mayo score criteria. Subjects must have failed or be intolerant of at least one of the following treatments for UC: Corticosteroids (oral or intravenous). Azathioprine or 6 mercaptopurine (6 MP). Anti TNF therapy. Exclusion Criteria: Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease. Subjects with disease limited to distal 15 cm. Subjects without previous treatment for UC (ie, treatment naïve). Subjects displaying clinical signs of fulminant colitis or toxic megacolon.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tofacitinib 10 mg BID<br> | Drug: tofacitinib<br>* 10 mg oral BID<br>* Other names: CP-690,550;|
| Placebo Comparator: Placebo BID<br> | Drug: Placebo<br>* Placebo oral BID<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Remission at Week 8 | Remission in participants was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of Ulcerative Colitis . It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible proctosigmoidoscopy and physician global assessment (PGA), each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Mucosal Healing at Week 8 | Mucosal healing in participants was defined by Mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. | Week 8 | 
| Percentage of Participants Achieving Clinical Response at Week 8 | Clinical response in participants was defined by a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Week 8 | 
| Percentage of Participants With Endoscopic Remission at Week 8 | Endoscopic remission in participants was defined by Mayo endoscopic subscore of 0. The Mayo endoscopic subscore consisted of the findings of centrally read flexible proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. | Week 8 | 
| Percentage of Participants With Clinical Remission at Week 8 | Clinical remission in participants was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Week 8 | 
| Percentage of Participants With Symptomatic Remission at Week 8 | Symptomatic remission was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and 0 subscore for both rectal bleeding and stool frequency. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Week 8 | 
| Percentage of Participants With Deep Remission at Week 8 | Deep remission in participants was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and 0 subscore for both rectal bleeding and endoscopic subscores. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Week 8 | 
| Partial Mayo Scores | A partial mayo score (mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA) and each grading from 0 to 3 with higher scores indicating more severe disease. | Baseline, Weeks 2, 4, 8 | 
| Change From Baseline in Partial Mayo Scores at Weeks 2, 4 and 8 | Change in Partial Mayo scores at Weeks 2, 4, 8 relative to baseline were reported. A Partial Mayo Score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA) with each graded from 0 to 3 with higher scores indicating more severe disease. | Baseline, Weeks 2, 4, 8 | 
| Change From Baseline in Total Mayo Score at Week 8 | Change in total Mayo scores at Week 8 relative to Baseline was reported. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. | Baseline, Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tofacitinib, CP-690, 550, Moderate to severe ulcerative colitis, phase 3 clinical trial, Mayo score