A Study Of PF-00547659 In Patients With Moderate To Severe Ulcerative Colitis

Study Overview
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Brief Summary
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To determine the dose or doses of PF-00547659 that will be the most effective to improve or halt the disease symptoms in patients with moderate to severe ulcerative colitis.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Parallel, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-00547659 In Subjects With Moderate To Severe Ulcerative Colitis (Turandot)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-00547659 SC Injection
* Drug: PF-00547659 SC Injection
* Drug: PF-00547659 SC Injection
* Drug: PF-00547659 SC Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with diagnosis of Ulcerative Colitis for 3 or more months. Ulcerative colitis must be active beyond the rectum. Must active Ulcerative Colitis with a Total Mayo Score of 6 to 12 points Exclusion Criteria: Pregnant or breast feeding. Diagnosis of indeterminate colitis or Crohn's Disease Subjects with history of colonic or small bowel obstruction or resection.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo delivered subcutaneous injection, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose Level 1<br> | Drug: PF-00547659 SC Injection<br>* Drug Dose Level 1 delivered subcutaneous injection, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose Level 2<br> | Drug: PF-00547659 SC Injection<br>* Drug Dose Level 2 delivered subcutaneous injection, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose Level 3<br> | Drug: PF-00547659 SC Injection<br>* Drug Dose Level 3 delivered subcutaneous injection, 3 doses separated by 4 weeks<br>|
| Experimental: Drug Dose Level 4<br> | Drug: PF-00547659 SC Injection<br>* Drug Dose Level 4 delivered subcutaneous injection, 3 doses separated by 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Clinical Remission at Week 12 | Clinical remission was defined as a Total Mayo Score of less than or equal (<=) 2 points with no individual subscore exceeding 1 point and rectal bleed subscore of 0 or 1. The Mayo Score is a tool designed to measure disease activity for ulcerative colitis (UC). Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at Week 12 | Clinical response was defined as a decrease from baseline of at least 3 points in Total Mayo Score with at least a 30 percent (%) change, accompanied by at least 1 point decrease or absolute score of 0 or 1 in rectal bleeding subscore. The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. | Week 12 | 
| Percentage of Participants With Mucosal Healing at Week 12 | Mucosal healing was defined as absolute Mayo subscore for endoscopy of 0 or 1. The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. | Week 12 | 
| Percentage of Participants With Absolute Partial Mayo Score of Less Than or Equal to (<=) 2 With no Individual Subscore More Than (>) 1 at Weeks 4, 8, and 12 | An absolute Partial Mayo Score of <=2 corresponds to remission. However, this endpoint was incorrectly stated in the protocol and instead of absolute Partial Mayo Score <=2, it was stated as change from baseline in Partial Mayo Score <=2. | Weeks 4, 8, and 12 | 
| Change From Baseline in Total Mayo Score at Week 12 | The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. | Baseline, Week 12 | 
| Percentage of Participants With Change From Baseline in Individual Mayo Subscores - Stool Frequency, Rectal Bleeding, and Physician's Global Assessment (PGA) - at Weeks 4, 8, and 12 | The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, PGA, findings on flexible sigmoidoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. Changes from baseline in the subscore of less than (<) 0, 0, and >0 corresponded to improvement (imp), no change (NC), and worsening (wors) in that specific subscore. | Baseline; Weeks (W) 4, 8, and 12 | 
| Percentage of Participants With Change From Baseline in Individual Mayo Subscore - Findings on Flexible Sigmoidoscopy - at Week 12 | The Mayo Score is a tool designed to measure disease activity for UC. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, PGA, findings on flexible sigmoidoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopic readings from the local and the central reader were considered for analysis. The central reading was used as the primary analysis and the local readings were used for the sensitivity analyses. Changes from baseline in the subscore of <0, 0, and >0 corresponded to improvement (imp), no change (NC), and worsening (wors) in that specific subscore. | Baseline, Week 12 | 
| Percent Change From Baseline in Fecal Calprotectin at Weeks 4, 8, and 12 | Fecal calprotectin was one of the pharmacodynamic (PD) biomarkers of the study. | Baseline, Weeks 4, 8, and 12 | 
| Percent Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Weeks 4, 8, and 12 | hsCRP was one of the PD biomarkers of the study. | Baseline; Weeks 4, 8, and 12 | 
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 12 | IBDQ: Psychometrically validated patient reported outcome (PRO) instrument for measuring disease-specific quality of life (QOL) in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is the sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL. | Baseline, Week 12 | 
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Scores at Week 12 | IBDQ: Psychometrically validated PRO instrument for measuring disease-specific QOL in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is the sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL. There are 4 individual domains under the IBDQ: bowel function (fx)/symptoms (score range of 10-70), systemic symptoms (score range of 5-35), emotional status/fx (score range of 12-84), and social fx (score range of 5-35). As with total score, higher scores indicate better QOL in that domain. | Baseline (BL), Week 12 | 
| Percentage of Participants With an Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score of More Than or Equal to (>=) 170 at Week 12 | IBDQ: Psychometrically validated PRO instrument for measuring disease-specific QOL in participants with inflammatory bowel disease. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is sum of each item score, ranged from 32 to 224 with higher score indicating better QOL. Positive change in total score indicated improvement in QOL. A score of >=170 corresponds to clinical remission. | Week 12 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs During the Treatment Period (Weeks 0-12) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Screening through to end of treatment period, up to 12 weeks | 
| Maximum Serum PF-00547659 Concentration Achieved |  | Weeks 0 (baseline), 2, 4,8, 12, 16, 20, 24, 28, 32, and 36; Early Withdrawal |