inflammatory bowel disease Ulcerative Colitis
Conditions
Interventions
Subjects will be assigned to one of two dose groups depending on their
remission status at baseline of Study A3921139:
• Tofacitinib 5 mg BID (subjects in remission).
• Tofacitinib 10 mg BID (all oth
Sponsors
Pfizer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet either inclusion criterion number 1 or 2, and all other following inclusion criteria to be eligible for enrollment into the study:;1. Subjects previously participated in Study A3921096 who either;• completed 52 week maintenance treatment in Study A3921096, or;• were early withdrawals from Study A3921096 and met treatment failure criteria defined by an increase in Mayo score of at least 3 points from baseline value of the maintenance study (A3921096), accompanied by an increase in rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 1 point (yielding an absolute endoscopic subscore of >=2), after a minimum of 8 weeks of treatment in the maintenance study. Note, endoscopic subscores based on central reading will be used to assess treatment failure.;2. Subjects who previously participated in the induction Study A3921094 or A3921095 who;• did not demonstrate clinical response after completing 8 weeks of treatment. Clinical response is defined by a decrease from baseline in Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1, and;• have an endoscopic subscore at Week 8 that is either the same or higher (worse) than the endoscopic subscore at Week 0 of Study A3921094 or A3921095. Note, endoscopic subscores based on central reading will be used to determine eligibility.;3. Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 4 weeks after the last dose of assigned treatment. ;4. Women of childbearing potential must have a negative pregnancy test prior to study enrollment.;5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, bowel movement diary calls, and other study procedures.;6. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study:;1. Subjects who had a major protocol violation in Study A3921094, A3921095 or A3921096.;2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn*s disease.;3. Subjects who have had surgery for UC or in the opinion of the investigator, are likely to require surgery for UC during the study period.;4. Subjects who are expected to receive any of prohibited medications, including medications that are either moderate to potent CYP3A inducers or inhibitors, during the study period as specified in the protocol. ;5. Subjects who are expected to receive live or attenuated virus vaccination during study period and for 6 weeks after last dose of study medication.;6. Women who are pregnant or breastfeeding, or planning to become pregnant during the study period.;7. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results (see protocol Appendix4).;8. Subjects with evidence of colonic malignancy or any dysplasia. Subjects with completely resected adenomatous polyp(s) may be eligible upon consultation with the sponsor.;9. Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable to comply with study procedures.;10. Any 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 for entry into this study.;11. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.;12. Subjects who are or interested in participating in other investigational studies during study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints • As this is an open label extension study, there will be no primary efficacy endpoint. • Incidence and severity of adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints • The proportion of subjects in remission at Month 2, Month 12, Month 24 and Month 36. Remission in this study is defined as a Mayo score smaller than or equal to 2 with no individual subscore >1, and rectal bleeding subscore of 0. • The proportion of subjects in remission at Month 2, Month 12, Month 24, and Month 36 among the following four subgroups of subjects based on the status at baseline of Study A3921139: 1) in remission defined by a total Mayo score smaller than or equal to 2 with no individual subscore >1, and rectal bleeding subscore of 0, 2) treatment failure defined by an increase in Mayo score of at least 3 points from baseline value of the maintenance study (A3921096), accompanied by an increase in rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 1 point (yielding an absolute endoscopic subscore of greater than or equal to 2), 3) all other subjects from maintenance study A3921096 neither in remission nor fulfilling the definition of treatment failure, and 4) non responders from induction studies A3921094 or A3921095. • The proportion of subjects in partial Mayo score (PMS) remission over time. • The proportion of subjects who achieve mucosal healing at Month 2, Month 12, Month 24 and Month 36. Mucosal healing is defined as a Mayo endoscopic subscore of 0 or 1. • The proportion of subjects with total score in Inflammatory Bowel Disease Questionnaire (IBDQ) greater than or equal to 170 over time. • Incidence of serious infections (defined as any infection AE that requires hospitalization or parenteral antimicrobials, or meets other criteria that require the infection to be classified as a serious adverse event (SAE)). • Incidence and severity of clinical laboratory abnormalities, and change from baseline in clinical laboratory values. • Incidence of vital sign abnormalities and change from baseline in vital signs. • Incidence of clinically significant changes | — |
Countries
Netherlands
Outcome results
None listed