A Study To Monitor Long-Term Treatment With PF-00547659

Study Overview
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Brief Summary
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This study provides open-label drug to eligible patients who have completed a prior study of PF-00547659. The primary endpoint for this study is long-term safety.

Detailed Description
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The rationale for conducting this open-label extension (OLE) study is primarily to evaluate long term safety of PF 00547659. This protocol also provides the opportunity for continued treatment for subjects responding to treatment from the feeder study. It also provides an opportunity for initial treatment for subjects randomized to placebo in the feeder study. This is a multi center Phase 2, open label, safety extension study for feeder studies which evaluate PF 00546759 in subjects with moderate to severe Crohn's disease. Subjects eligible for this study will have completed the 12 week double blind induction period in study A7281006 and will be stratified by responders or non responders based on change in CDAI in that study, without unblinding treatment assignment from study A7281006. Additionally, subjects who have completed study A7281008 with a clinical response, as defined by that protocol, will also be eligible for this study and treated as responders. All subjects entering this study must have discontinued immunosuppressant therapy. Subjects entering this study will be given a 75 mg SC dose at baseline and then every 4 weeks through Week 72. After the active treatment period, the subjects will enter a 24 month follow up period including 6 monthly visits followed by 18 month extended contact (every 6 month telephone contacts). At Week 96, subjects will undergo an End of Study visit but will continue the every 6 month telephone contacts until Week 168.

Official Title
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A Multicenter Open-label Extension Study To Assess Long-term Safety Of PF-00547659 In Subjects With Crohn's Disease OPERA II

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: PF-00547659


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between 18 and 76 years of age. Subjects previously enrolled in study A7281006 who have completed the blinded 84 day (12 week) induction period or in study A7281008 who have completed Week 12 and have demonstrated a clinical response as defined by that protocol. Exclusion Criteria: Subjects that have completed Day 84 (Week 12) of a PF-00547659 study 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 hinder entry or participation in this study. Subjects who are taking any dose of azathioprine, 6-mercaptopurine or methotrexate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Treatment<br>Subjects eligible for this study will have completed the 12 week double blind induction period in study A7281006 and will be stratified by responders or non responders based on change in CDAI in that study, without unblinding treatment assignment from study A7281006. Additionally, subjects who have completed study A7281008 | Drug: PF-00547659<br>* 75 mg SC once monthly for 72 weeks. Subjects may escalate to 225 mg or de-escalate to 22.5 mg one time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With On-Treatment Adverse Events (AEs), AEs Led to Withdrawal, and Serious Adverse Events (SAEs) | AEs included adverse drug reactions, illnesses with onset during the study, exacerbation of previous illnesses, clinically significant changes in physical examination findings and abnormal objective test findings (ECG, laboratory). An SAE was defined as any AE at any dose that resulted in death; was life threatening (immediate risk of death); required in-subject hospitalization or prolongation of existing hospitalization; resulted in a persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect. | From start of study treatment up to Week 72 (Treatment Period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Anti-Drug (PF-00547659) Antibodies | Positive Anti-Drug Antibodies result was defined as ADA titre value greater than or equal to (>=) 4.64 at at least one of the time points. | Baseline up to Week 96 | 
| Serum Trough Concentrations of PF-00547659 Versus Time | Serum trough concentrations of PF-00547659 were analyzed using population Pharmacokinetic (PK) methodology. | Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84,88,92,96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active Crohn's disease, Anti-TNF Refractory, Immunosuppressant Refractory