The Safety And Efficacy Of Maintenance Therapy With CP-690,550

Study Overview
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Brief Summary
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This study investigates safety and efficacy of CP-690,550 in adult patients with moderate to severe Crohn's disease who completed the double-blind induction treatment in Study A3921083 and achieved clinical response-100 and/or clinical remission (CDAI<150) at Week 8.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Centre Study To Investigate The Safety And Efficacy Of CP-690,550 For Maintenance Therapy In Subjects With Moderate To Severe Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: CP-690,550
* Drug: CP-690,550


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who met study entry criteria, and who completed Week 8 visit of Induction Study A3921083. Subjects who achieve clinical response-100 (reduction in CDAI by 100 points) and/or clinical remission (CDAI<150) in Study A3921083. Women of childbearing potential must test negative for pregnancy prior to study enrolment. Exclusion Criteria: Subjects who had major protocol violation (as determined by the Sponsor) in the A3921083 study. Subjects likely to require any type of surgery during the study period. Fecal culture/toxin assay indicating presence of pathogenic infection.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo BID<br> | Drug: Placebo<br>* oral tablets twice daily<br>|
| Experimental: 5mg BID<br> | Drug: CP-690,550<br>* oral tablets twice daily<br>|
| Experimental: 10mg BID<br> | Drug: CP-690,550<br>* oral tablets twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26 | Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score <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 anti-diarrheal 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. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score <150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 4, 8, 12 and 20 | 
| Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 4, 8, 12, 20 and 26 | 
| Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Clinical remission was a CDAI score <150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 4, 8, 12, 20 and 26 | 
| Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Clinical remission was a CDAI score <150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 4, 8, 12, 20 and 26 | 
| Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase | Clinical remission was a CDAI score <150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 20 and 26 | 
| Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase | Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of 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 scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 20 and 26 | 
| CDAI Score by Week | CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity | Baseline and Weeks 4, 8, 12, 20 and 26 | 
| Change From Baseline in CDAI Score by Week | CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity | Weeks 4, 8, 12, 20 and 26 | 
| Kaplan-Meier Estimate of the Rate of Time to Relapse | Time to relapse was defined as increase in CDAI of more than (>)100 points from the maintenance phase baseline and a CDAI score of >220 points, or an increase to or above the baseline CDAI score in A3921083. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Weeks 4, 8 12, 20 and 26 | 
| Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline | Clinical remission was a CDAI <150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body eight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. | Week 26 | 
| C-Reactive Protein (CRP) by Week | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline and Weeks 4, 8, 12, 20 and 26 | 
| Change From Baseline in CRP by Week | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Weeks 4, 8, 12, 20 and 26 | 
| Fecal Calprotectin by Week | Fecal calprotectin is an inflammatory marker for the gastrointestinal tract and considered as a measurement of neutrophil migration to the gastrointestinal tract. Higher values indicate more serious inflammation. | Baseline and Weeks 8, 12 and 26 | 
| Change From Baseline in Fecal Calprotectin by Week | Fecal calprotectin is an inflammatory marker for the gastrointestinal tract and considered as a measurement of neutrophil migration to the gastrointestinal tract. Higher values indicate more serious inflammation. | Weeks 8, 12 and 26 | 
| Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Plasma samples were collected from participants for the determination of tofacitinib concentrations. Only samples from tofacitinib-treated participants were subsequently analyzed. Plasma concentration data are summarized by nominal sample collection times specified in the protocol, and actual sample collection times may be different. | Pre-dose, 20 minutes, 40 minutes, 1 hour and 2 hours post-dose at Weeks 12 and 26/early termination visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tofacitinib, Xeljanz, CP-690,550, maintenance therapy