A multi-center, open-label study of CP-690,550 in subjects with moderate to severe ulcerative colitis

Phase 1

Conditions: lcerative colitis
MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2011-004581-14-BE

Lead Sponsor: Pfizer Inc, 235 East 42nd Street, New York, New York 10017

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 944

Inclusion Criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 738
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 162

Exclusion Criteria

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 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 Appendix 4).
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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of long-term tofacitinib therapy in subjects with UC.;Secondary Objective: To evaluate the efficacy of long term tofacitinib therapy in subjects with UC.<br><br>To evaluate the effect of long term tofacitinib therapy on quality-of-life in subjects with UC.<br>;Primary end point(s): As this is an open label extension study, there will be no primary efficacy endpoint.<br><br>Incidence and severity of adverse events. ;Timepoint(s) of evaluation of this end point: Ongoing incidence and severity of adverse events

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - The proportion of subjects in remission at Months 2, 12, 24 and 36. <br>- The proportion of subjects in clinical remission at Month 2, Month 12, Month 24 and Month 36. Clinical remission in this study is defined as a Mayo score =<2 with no individual subscore >1.<br>- Proportion of subjects in partial Mayo score (PMS) remission over time. <br>- Proportion of subjects who achieve mucosal healing at Months 2, 12, 24 and 36.<br>- Proportion of subjects with total score in IBDQ =170 over time.<br>- Incidence of serious infections.<br>Other secondary, exploratory, pharmacokinetic, biomarker, Health Outcome and safety endpoints are described within the protocol<br>;Timepoint(s) of evaluation of this end point: Partial Mayo Scores (PMS) are measured at Months 2, 12, 24, 36 and every 3 months afterwards.<br>All other secondary endpoints are measured at Months 2, 12, 24 and 36.

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