Long-Term Safety Of PF-00547659 In Ulcerative Colitis

Study Overview
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Brief Summary
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Subjects with Ulcerative Colitis who have completed an induction study with PF-00547659 will receive an additional 144 weeks of open-label treatment to evaluate the long-term safety of the drug.

Official Title
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A Multicenter Open-Label Extension Study To Assess Long-Term Safety Of PF-00547659 In Subjects With Ulcerative Colitis (TURANDOT II)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: 75mg SHP647 (PF-00547659)
* Drug: 225mg SHP647 (PF-00547659)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between 18 and 66 years of age. Subjects previously enrolled in study A7281009 (NCT01620255) who have completed the 84 day (12 week) induction period. Exclusion Criteria: Subjects that have completed Day 84 (Week 12) of study A7281009 but have experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would preclude entry or participation in this study. Subjects who are taking any dose of Azathioprine (AZA), 6-mercaptopurine(6 MP) or Methotrexate (MTX).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 66 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP647 75 mg<br>Participants will receive 75 milligrams (mg) of SHP647 subcutaneous (SC) injection every 4 weeks for 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen. During the first 72 weeks, a one time dose escalation to 225 mg of SHP647 SC injection every 4 weeks is allowed after 8 weeks of the study for participants who experience clinical deterioration or unacceptably low level of response to the investigational product. The decision to escalate will be guided by the response and relapse criteria tempered by clinical judgment. Following the first 72 weeks, participants will receive 75 mg of SHP647 SC injection every 4 weeks for an additional 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen. | Drug: 75mg SHP647 (PF-00547659)<br>* 75 mg sterile liquid injected subcutaneously every 4 weeks.<br>|
| Experimental: SHP647 225 mg<br>Participants will receive 225 mg of SHP647 SC injection every 4 weeks for 72 weeks followed by 75 mg of SHP647 SC injection every 4 weeks for an additional 72 weeks in the anterolateral right/left thigh or the deltoid area or the abdomen. | Drug: 225mg SHP647 (PF-00547659)<br>* 225 mg sterile liquid injected subcutaneously every 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Who Withdrew From Treatment Due to Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who was administered a product or medical device; the event did not need to necessarily have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly/birth defect. Number of participants with TEAEs, STEAEs, and those withdrew from treatment due to TEAEs were reported. | From start of study drug administration up to 168 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Mucosal Healing at Week 16 | Mucosal healing was defined as an absolute Mayo subscore for endoscopy of 0 or 1 (based on centrally read score) as assessed by flexible sigmoidoscopy or colonoscopy. The Mayo score is a tool designed to measure disease activity for ulcerative colitis (UC). The Mayo scoring system ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy, and physician's global assessment [PGA]) each graded 0 to 3 with the higher score indicating more severe disease activity. The percentage of participants with mucosal healing at week 16 was reported. | Week 16 | 
| Serum Trough Concentrations of SHP647 Versus Time | Serum trough concentrations of SHP647 versus time was reported. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 and 156 | 
| Number of Participants With Positive Anti-drug (SHP647) Antibodies (ADA) | The anti-drug antibodies (ADA) positive was defined as ADA log base 2 titer greater than or equal to (>=) 4.64. The number of participants with positive ADA was reported. | Baseline, Week 8, 16, 24, 40, 48, 64 and 156 | 
| Number of Participants With Positive Neutralizing Antibodies (NAb) | The positive Neutralizing Antibodies (NAb) was defined as NAb titer greater than or equal to (>=) 0.903. The number of participants with NAb was reported. Here inconclusive refers to participants who were neither reported as positive nor negative for NAb and anti-drug antibodies (ADA) positive was defined as ADA log base 2 titer greater than or equal to (>=) 4.64. | Baseline, Week 8, 16, 24, 40, 48, 64 and 156 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-TNF Refractory, Active Ulcerative Colitis, Immunosuppressant Refractory