A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Centre Study To Investigate The Safety And Efficacy Of CP-690,550 For Induction Therapy In Subjects With Moderate To Severe Crohn's Disease
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Crohn's Disease
- Sponsor
- Pfizer
- Enrollment
- 280
- Locations
- 136
- Primary Endpoint
- Percentage of Participants in Clinical Remission (as Defined by a Crohn's Disease Activity Index [CDAI] Score of Less Than [<] 150 Points) at Week 8
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study investigates safety and efficacy of CP-690,550 in adult patients with moderate to severe Crohn's disease. The study hypothesis is that at least one dose of the tested drug is more effective than placebo (inactive drug).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects between the ages of 18 and 75 years at screening (upper age limit will be 64 years in India and 65 years in the Netherlands).
- •Subjects with clinical diagnosis of Crohn's disease for at least 6 months prior to screening.
- •Subjects with active moderate to severe ileal, ileocolic, or colonic CD defined by a baseline score of Crohn's Disease Activity Index (CDAI) of 220 to 450 at baseline.
Exclusion Criteria
- •Diagnosis of indeterminate colitis, ulcerative colitis (UC), or clinical findings suggestive of UC.
- •Subjects diagnosed with Crohn's disease but without previous exposure to treatment (i.e., treatment-naïve).
- •Subjects receiving the following treatment for Crohn's disease:
- •Azathioprine, 6-mercaptopurine or methotrexate within 2 weeks prior to baseline.
- •Anti-TNFα therapy within 8 weeks prior to baseline.
- •Interferon therapy within 8 weeks prior to baseline.
- •Cyclosporine, mycophenolate, or tacrolimus within 4 weeks prior to baseline.
- •Intravenous corticosteroids within 2 weeks prior to baseline.
Arms & Interventions
Placebo BID
Intervention: Placebo
5mg BID
Intervention: CP-690,550
10mg BID
Intervention: CP-690,550
Outcomes
Primary Outcomes
Percentage of Participants in Clinical Remission (as Defined by a Crohn's Disease Activity Index [CDAI] Score of Less Than [<] 150 Points) at Week 8
Time Frame: Week 8
Clinical remission was a CDAI \< 150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.
Secondary Outcomes
- EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit(Baseline, Week 8/ET visit)
- Percentage of Participants in Clinical Remission (CDAI <150) at Weeks 2 and 4(Weeks 2 and 4)
- Percentage of Participants With ≥16 Point Increase From Baseline in IBDQ Total Score at Week 8/ET Visit(Week 8/ET visit)
- Percentage of Participants Achieving Clinical Response-70 (as Defined by a Decrease in CDAI Score of at Least 70 Points From Baseline) at Weeks 2, 4, and 8(Baseline, Weeks 2, 4, and 8)
- Percentage of Participants Achieving Either Clinical Response-100 or Clinical Remission (CDAI<150) at Weeks 2, 4, and 8(Baseline, Weeks 2, 4, and 8)
- Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit(Baseline, Week 8/ET visit)
- Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA)(Baseline, Week 8/ET visit)
- Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category(Week 8/ET visit)
- Percentage of Participants Achieving Clinical Response-100 (as Defined by a Decrease in CDAI Score of at Least 100 Points From Baseline) at Weeks 2, 4, and 8(Baseline, Weeks 2, 4, and 8)
- C-Reactive Protein (CRP) Serum Concentrations at Weeks 2, 4, and 8(Weeks 2, 4, and 8)
- Calprotectin Fecal Concentrations at Weeks 2, 4, and 8(Weeks 2, 4, and 8)
- Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit(Pre-dose, 20 minutes, 40 minutes, 1 hour, and 2 to 3 hours post-dose on Day 1 and Week 8/ET visit)
- Percentage of Participants With an IBDQ Total Score of Greater Than or Equal to (≥) 170 at Week 8/ET Visit(Week 8/ET visit)
- Change From Baseline EQ-5D VAS Scores at Week 8/ET Visit Using ANCOVA(Baseline, Week 8/ET visit)
- CDAI Scores at Weeks 2, 4, and 8(Weeks 2, 4, and 8)
- Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit(Baseline, Week 8/ET visit)
- Change From Baseline EQ-5D Utility Scores at Week 8/ET Visit Using ANCOVA(Baseline, Week 8/ET visit)
- Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA(Baseline, Week 8/ET visit)
- EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 8/ET Visit(Baseline, Week 8/ET visit)