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

• ClinicalTrials.gov Identifier: NCT01393899
• Recruitment Status: Completed
• First Posted: July 13, 2011
• Results First Posted: January 9, 2017
• Last Update Posted: January 9, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: July 12, 2011
• First Posted Date: July 13, 2011
• Results First Submitted Date: August 29, 2016
• Results First Posted Date: January 9, 2017
• Last Update Posted Date: January 9, 2017
• Study Start Date: March 2012
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2016)

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 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: July 12, 2011): The proportion of subjects maintaining clinical response-100, as defined by a decrease in CDAI score at least 100 points from A3921083 baseline, or being in clinical remission, as defined by a CDAI score less than 150, at Week 26. [ Time Frame: Week 26 ]

Current Secondary Outcome Measures (submitted: November 10, 2016)

• Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 [ Time Frame: 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.
• Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 [ Time Frame: 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.
• Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 [ Time Frame: 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.
• Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study [ Time Frame: 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.
• Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase [ Time Frame: Weeks 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.
• 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 [ Time Frame: Weeks 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 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.
• CDAI Score by Week [ Time Frame: Baseline and Weeks 4, 8, 12, 20 and 26 ]
  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
• Change From Baseline in CDAI Score by Week [ Time Frame: Weeks 4, 8, 12, 20 and 26 ]
  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
• Kaplan-Meier Estimate of the Rate of Time to Relapse [ Time Frame: Weeks 4, 8 12, 20 and 26 ]
  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.
• Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline [ Time Frame: Week 26 ]
  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.
• C-Reactive Protein (CRP) by Week [ Time Frame: Baseline and Weeks 4, 8, 12, 20 and 26 ]
  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.
• Change From Baseline in CRP by Week [ Time Frame: Weeks 4, 8, 12, 20 and 26 ]
  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.
• Fecal Calprotectin by Week [ Time Frame: Baseline and Weeks 8, 12 and 26 ]
  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.
• Change From Baseline in Fecal Calprotectin by Week [ Time Frame: Weeks 8, 12 and 26 ]
  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.
• Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose [ Time Frame: Pre-dose, 20 minutes, 40 minutes, 1 hour and 2 hours post-dose at Weeks 12 and 26/early termination visit ]
  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.

Original Secondary Outcome Measures (submitted: July 12, 2011)

• The proportion of subjects maintaining clinical response-100 or being in clinical remission at Weeks 4, 8, 12, 20 and 26 from the A3921083 Baseline. [ Time Frame: Week 4, 8,12,20 and 26 ]
• The proportion of subjects maintaining at least a clinical response-100 at Weeks 4, 8, 12, 20 and 26. [ Time Frame: Week 4, 8,12, 20 and 26 ]
• The proportion of subjects in clinical remission at Weeks 4, 8, 12, 20 and 26. [ Time Frame: Weeks 4, 8, 12, 20 and 26 ]
• The proportion of subjects in clinical remission at Weeks 4, 8, 12, 20, and 26 among subjects in clinical remission at baseline of maintenance study. [ Time Frame: Weeks 4, 8, 12, 20 and 26 ]
• The proportion of subjects in sustained clinical remission in the maintenance phase. Sustained clinical remission is defined as being in clinical remission at both Weeks 20 and 26. [ Time Frame: Weeks 20 and 26 ]
• The proportion of subjects achieving sustained clinical response in the maintenance phase. Sustained clinical response is defined as having at least a clinical response-100 at both Weeks 20 and 26 from the A3921083 Baseline. [ Time Frame: Weeks 20 and 26 ]
• The proportion of subjects achieving a steroid-free clinical remission at Week 26 of the maintenance phase among subjects on steroids at baseline. [ Time Frame: Week 26 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Safety And Efficacy Of Maintenance Therapy With CP-690,550
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: Placebo
  oral tablets twice daily
• Drug: CP-690,550
  oral tablets twice daily

Study Arms

• Placebo Comparator: Placebo BID
  Intervention: Drug: Placebo
• Experimental: 5mg BID
  Intervention: Drug: CP-690,550
• Experimental: 10mg BID
  Intervention: Drug: CP-690,550

• Publications *: Panés J, Sandborn WJ, Schreiber S, Sands BE, Vermeire S, D'Haens G, Panaccione R, Higgins PDR, Colombel JF, Feagan BG, Chan G, Moscariello M, Wang W, Niezychowski W, Marren A, Healey P, Maller E. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017 Jun;66(6):1049-1059. doi: 10.1136/gutjnl-2016-312735. Epub 2017 Feb 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2016): 180
• Original Estimated Enrollment (submitted: July 12, 2011): 90
• Actual Study Completion Date: July 2015
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Israel, Japan, Korea, Republic of, Netherlands, South Africa, Spain, Ukraine, United States
• Removed Location Countries: Croatia, India

Administrative Information

• NCT Number: NCT01393899
• Other Study ID Numbers: A3921084; 2011-001754-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2016