inflammatory bowel disease Ulcerative colitis
Conditions
Interventions
Subjects will be administered one or more SC doses of the study drug at day 1
(baseline) and then every 4 weeks during the treatment period.
Sponsors
Shire
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study: 1.Subjects previously enrolled in study A7281009 who have completed the blinded 84-day (12-week) induction period. 2.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 3.Male and/or female subjects between the ages of 18 and older and 66 years and younger at the time of informed consent if they were previously enrolled in study A7281009. 4. All women of childbearing potential (WOCBP) as determined during study A7281009 (data must be available as source documents for this study) must have a negative urine pregnancy test result at the Baseline visit and throughout the duration of this study (defined as the time of the signing of the ICD through the end of this study). 5. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the duration of the study (defined as the time of the signing of the ICD through the conclusion of onsite subject participation or for approximately 6 months from the last dose of investigational product for any subject who discontinues early from the study). A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.;*Women of childbearing potential (WOCBP) must have a negative urine pregnancy test result at baseline. WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.;* Women of non-childbearing potential (WONCBP) do not require a urine pregnancy test and must meet at least one of the following criteria:;* Have undergone hysterectomy or bilateral oophorectomy;;* Have medically confirmed ovarian failure; or;* Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).;6. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in this study: 1. 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. 2. Subjects who are taking any dose of AZA, 6-MP or MTX. 3. Pregnant or breastfeeding women. 4. Males and females of childbearing potential not using higly effective contraception or not agreeing to continue highly effective contraception through the conclusion of onsite subject participation or for approximately 6 months from the last dose of investigational product for any subject who discontinues early from the study). 5. Evidence of right or left heart failure based on echocardiographic assessments conducted as part of a prior study of PF-00547659. 6. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate entry into this study. 7. Received any prohibited treatment during study A7281009 that, in the opinion of the investigator, compromised the safety or efficacy of this study. 8. Planned live (attenuated) vaccination during the course of the study. 9. Planned major elective medical or surgical procedure during the course of this study. 10. Participation in other interventional studies during participation in this study. 11. The inability to complete any of the five neurological assessments without a clear explanation (e.g. broken leg, sprained wrist, etc).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of on treatment AEs, AEs leading to withdrawal, and SAEs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints Immunogenicity * Frequency of the development of anti drug antibodies (ADAs) and neutralizing antibodies (Nabs). Pharmacokinetics * Serum trough concentrations of PF 00547659 via listings and plots. Mucosal Healing * Proportion of subjects with mucosal healing at Week 16 (defined as absolute Mayo subscore for endoscopy of 0 or 1). Exploratory Efficacy Endpoints * Assessment of the durability of response based upon Clinical Remission and Clinical Response based upon Total Mayo score assessed at Week 16 [28 weeks from initial dose] in subjects with a Clinical Response in study A7281009. * Non-Responders from study A7281009 will also be assessed at Week 16 for Clinical Remission and Clinical Response. * Assessment of Clinical Remission and Clinical Response based upon the partial Mayo Score in all subjects at Week 40, Week 92 and Week 144. * Simple Clinical Colitis Activity Index (SCCAI) will be assessed at monthly visits. * Partial and Mayo subscores will also be assessed. Exploratory Pharmacodynamic Endpoints * Blood samples will be collected prior to dosing at baseline and every 4 weeks to Week 24, Week 32 and Week 72 to measure hsCRP. Also, stool samples will be collected at the time points noted above to measure fecal calprotectin. Blood samples will be collected at baseline, Week 4 (Visit 2) and Week 16 (Visit 5) to measure soluble MAdCAM. Exploratory Biomarkers * Analyses relevant to the understanding and treatment of UC may be conducted on the portion of stool samples remaining after calprotectin analysis. * Blood will be collected at Visits 2, 5 and 19 for multiplex analyses of RNA transcripts and proteins associated with UC, inflammation and mechanism of drug activity. * Optional biopsies will be taken at Visit 5 to assess RNA transcripts and proteins associated with UC, inflammation and mechanism of drug activity. | — |
Countries
Netherlands
Outcome results
None listed