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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Drug: CP-690,550

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3050
    • Royal Melbourne Hospital
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Public Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Wien, Austria, 1090
    • AKH Wien Universitaetsklinik fuer Innere Medizin III
• Bulgaria
  • Sofia, Bulgaria, 1797
    • MBAL Sofiamed OOD, Otdelenie po gastroenterologia
  • Sofia, Bulgaria, 1000
    • 4 MBAL Parvo vatreshno otdelenie
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6R3
      • Office of Dr. David C. Pearson
    • Victoria, British Columbia, Canada, V8V 3P9
      • PerCuro Clinical Research Ltd.
    • Victoria, British Columbia, Canada, V8V 3P9
      • Office of Drs. Ranjith Andrew Singh and Jamie D. Papp,
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3G1A4
      • Montreal General Hospital - McGill University Health Centre
• Czech Republic
  • Hradec Kralove, Czech Republic, 50012
    • Hepato-Gastroenterologie HK, s.r.o.
  • Hradec Kralove, Czech Republic, 50012
    • RDG centrum s.r.o. (Radiology only)
  • Hradec Králové, Czech Republic, 50012
    • Medial Pharma spol.s.r.o. (Pharmacy only)
• France
  • Lille Cedex, France, 59037
    • Hopital Huriez CHRU de Lille
  • Pessac Cedex, France, 33064
    • Hôpital Haut-Lévêque/Service d hépato-gastroentérologie
• Germany
  • Berlin, Germany, 12200
    • Charité - Campus Benjamin Franklin
  • Berlin, Germany, 10117
    • Charite - Campus Berlin Mitte
  • Berlin, Germany, 13353
    • Charite, Universitaetsmedizin Berlin, Campus Virchow-Klinikum
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm, Klinik Fuer Innere Medizin I
• Greece
  • Kolonaki Athens, Greece, 106 76
    • General Hospital of Athens "Evangelismos",1st Gastroenterology Department
• Hungary
  • Budapest, Hungary, 1136
    • Pannónia Magánorvosi Centrum Kft
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszat es Gastroenterologia
  • Budapest, Hungary, H-1044
    • Laboratorium Kft. Fovarosi és Pest Megyei Mikrobiologiai Laboratorium
  • Budapest, Hungary, H-1076
    • Peterfy Sandor Utcai Korhaz, Rendelointezet es Baleseti Kozpont, I. sz. Belgyogyaszat
  • Gyongyos, Hungary, 3200
    • Bugat Pal Korhaz Egeszsegugyi Szolgaltato Kozhasznu Nonprofit Kft.,
  • Kaposvár, Hungary, H-7400
    • Laboratórium Kft. Somogy Megyei Mikrobiológiai Laboratórium
  • Szekszard, Hungary, 7100
    • Clinfan Kft.
• Israel
  • Jerusalem, Israel, 91031
    • Digestive Disease Institute
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Tel -Aviv, Israel, 64932
    • Tel Aviv Sourasky Medical Center
• Japan
  • Chiba, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Hokkaido, Japan, 060-0033
    • Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
      • The Hospital of Hyogo College of Medicine
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
      • National Hospital Organization Sendai Medical Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center, Division of Gastroenterology, Department of Internal Medicine
  • Seoul, Korea, Republic of, 138-736
    • ASAN Medical Center,Division of Gastroenterology,Department of Internal Medicine
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Amsterdam, Netherlands, 1081HV
    • VU University Medical Center
• South Africa
  • Durban, South Africa, 4091
    • Parklands Medical Centre
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7708
      • Kingsbury Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08036
    • Comite Etico de Investigacion Clinica
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa
• Ukraine
  • Donetsk, Ukraine, 83017
    • Donetsk National Medical University n.a M. Gorky, Faculty of Internal Medicine #2
  • Odesa, Ukraine, 65117
    • Municipal Institution "Odesa Regional Clinical Hospital", Odesa Regional Centre of Gastroenterology.
  • Vinnitsa, Ukraine, 21029
    • Medical Clinical Research Center of Medical Center "Health Clinic" LLC
• United States
  • California
    • Anaheim, California, United States, 92801
      • ACMG Endoscopy Center
    • Anaheim, California, United States, 92801
      • ACRI - Phase I, LLC
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute-Phase 1, LLC
    • Cypress, California, United States, 90630
      • West Coast Clinical Trials
    • Oceanside, California, United States, 92056
      • Alliance Clinical Research
  • Colorado
    • Lafayette, Colorado, United States, 80026
      • Clinical Research of the Rockies
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Clearwater, Florida, United States, 33756
      • Gasteroenterology Consultants of Clearwater
    • Clearwater, Florida, United States, 33756
      • West Coast Endoscopy Center
    • Gainesville, Florida, United States, 32608
      • Shands Endoscopy Center
    • Gainesville, Florida, United States, 32610-0214
      • Shands Hospital at the University of Florida
    • Gainesville, Florida, United States, 32610
      • Shands Medical Plaza and Cancer Center
    • Gainsville, Florida, United States, 32610
      • University of Florida - College of Medicine
    • Naples, Florida, United States, 34102
      • Gastroenterology Group of Naples
    • Naples, Florida, United States, 34102
      • Gulfshore Endoscopy Center (Endoscopies Only)
    • Orange Park, Florida, United States, 32073
      • North Florida Gastroenterology Research, LLC
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
  • Georgia
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia, LLC
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center, Digestive Health
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Endoscopy Center
    • Chevy Chase, Maryland, United States, 20815
      • Metropolitan Gastroenterology Group, PC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2701
      • East Ann Arbor Health and Geriatrics Center
    • Ann Arbor, Michigan, United States, 48109-5000
      • University of Michigan Health Systems
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
    • Troy, Michigan, United States, 48098
      • Surgical Centers of Michigan
  • New York
    • Great Neck, New York, United States, 11021
      • NYU Langone Nassau Gastroenterology Associates
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley, PC
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Cleveland, Ohio, United States, 44106
      • Investigational Drug Services - University Hospitals Case Medical Center
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology
  • Texas
    • Tyler, Texas, United States, 75701
      • Digestive Health Specialists of Tyler
    • Tyler, Texas, United States, 75701
      • Endoscopy Center of Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah HSC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Cardiology Consultants
    • Norfolk, Virginia, United States, 23502
      • Digestive & Liver Desease Specialists
    • Washington DC, Virginia, United States, 20006
      • Metropolitan Gastroenterology Group, P C
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • The Center for Digestive Health
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research - GI Associates, LLC
    • Wauwatosa, Wisconsin, United States, 53226
      • Allegiance Research Specialists
    • Wauwatosa, Wisconsin, United States, 53226
      • GI Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Panes 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 12, 2011
• First Submitted That Met QC Criteria: July 12, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 10, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: tofacitinib; Xeljanz; CP-690,550; maintenance therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921084; 2011-001754-28 (EudraCT Number)