Back to resultsA Multicenter Trial Comparing REMICADE (Infliximab) and Placebo in the Prevention of Recurrence in Crohn's Disease (CD) Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence
Primary Purpose
Crohn's Disease
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Infliximab
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Crohn's Disease focused on measuring Crohn's Disease, Inflammatory Bowel Disease, infliximab, TNF-alpha
Eligibility Criteria
Inclusion Criteria:
- Have a documented diagnosis of CD confirmed by endoscopic, histologic and/or radiologic studies prior to resection or by tissue obtained at resection
- Have undergone an ileocolonic surgical resection
- Patients must also be at an increased risk of recurrence of active CD
- Patients must not have previously discontinued infliximab as a result of tolerability issues or they must be naive to treatment with infliximab. Provided patients meet the above criteria pertaining to infliximab, they are eligible to enroll if they received prior treatment with adalimumab and/or certolizumab
- Patients must undergo screening for HBV
- Baseline CDAI < 200
- Have adequate blood and liver test values
Exclusion Criteria:
- Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening
- Have a chest radiograph within 3 months prior to the first infusion of study agent that shows a clinically significant abnormality, such as a malignancy or infection, or any abnormalities suggestive of TB
- Have macroscopically active CD which was not resected at the time of surgery
- Do not meet the criteria for being at an increased risk of postoperative recurrence of active CD as outlined in the inclusion criteria
- Have evidence of an active infection at the time of randomization or have had a serious infection not related to CD (e.g., hepatitis, pneumonia, or pyelonephritis), within 6 months prior to screening
- Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening
- Have any known malignancy or history of malignancy within the 5-year period prior to screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence)
- Have any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Infliximab
Placebo
Arm Description
Infliximab Type=equal unit=mg number=5 form=intravenous infusion route=intravenous use once every 8 weeks
Placebo Type=equal unit=mg number=5 form=intravenous infusion route=intravenous use once every 8 weeks
Outcomes
Primary Outcome Measures
Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 76
CR criteria:1) A >=70-point increase from baseline in CDAI score [in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities];2)A CDAI score >=200;3)Evidence of endoscopic recurrence [ileal Rutgeerts score of >=i2 at anastomotic site or its equivalent elsewhere in GI tract] and 4)A negative stool test for C. difficile toxin (if, in the opinion of the investigator, the participant's symptoms are predominantly diarrheal); or at least 1 of followings:1) developing a new draining external fistula;2)re-opening and draining of a previously existing external fistula;3)developing a new internal fistula;4)developing a new perianal abscess or 5)developing a new intra-abdominal abscess more than 3 months after date of index surgery. In addition, participants who had a treatment failure [initiated a prohibited CD medication, had prohibited use of CD medication, or had surgery for CD] before or at Week 76 were considered to have clinical recurrence.
Secondary Outcome Measures
Percentage of Participants With Endoscopic Recurrence of CD Prior to or at Week 76
Endoscopic recurrence is defined as an ileal Rutgeert's score of >= i2 either at the anastomotic site or elsewhere in the gastrointestinal tract. In addition, participants who had a treatment failure (initiated a prohibited CD medication, had a prohibited use of a CD medication, or had a surgery for CD) prior to Week 76, and who developed a new draining external fistula or re-opening and draining of a previously existing external fistula or developed a new internal fistula, new perianal abscess or new intra-abdominal abscess more than 3 months after the date of the index surgery were considered to have had endoscopic recurrence prior to or at Week 76.
Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 104
CR criteria:1) A >=70-point increase from baseline in CDAI score [in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities];2)A CDAI score >=200;3)Evidence of endoscopic recurrence [ileal Rutgeerts score of >=i2 at anastomotic site or its equivalent elsewhere in GI tract] and 4)A negative stool test for C. difficile toxin (if, in the opinion of the investigator, the participant's symptoms are predominantly diarrheal); or at least 1 of followings:1) developing a new draining external fistula;2)re-opening and draining of a previously existing external fistula;3)developing a new internal fistula;4)developing a new perianal abscess or 5)developing a new intra-abdominal abscess more than 3 months after date of index surgery. In addition, participants who had a treatment failure [initiated a prohibited CD medication, had prohibited use of CD medication, or had surgery for CD]before or at Week 104 were considered to have clinical recurrence.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01190839
Brief Title
A Multicenter Trial Comparing REMICADE (Infliximab) and Placebo in the Prevention of Recurrence in Crohn's Disease (CD) Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence
Official Title
Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing REMICADE (Infliximab) and Placebo in the Prevention of Recurrence in Crohn's Disease Patients Undergoing Surgical Resection Who Are at Increased Risk of Recurrence
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Terminated
Why Stopped
Study is terminated as per Sponsor's Decision.
Study Start Date
November 2010 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Biotech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
REMICADE (infliximab) is a drug used to treat active Crohn's disease and is being tested in an experiment to see if it may be useful in preventing relapse of Crohn's disease after surgical resection. This study will compare the effects (both good and bad) of REMICADE (infliximab) to those of placebo. Placebo looks like the drug being studied but has no active ingredients.
Detailed Description
The purpose of this study is to assess the effects of REMICADE (infliximab) in preventing relapse of Crohn's disease after surgical resection. Patients will be assigned to a group that will initially receive either infliximab or placebo. Each patient who is allowed to join the study is put into a group by chance (randomly), like flipping a coin. There is a possibility that patients can receive both the study drug and placebo at different times in the study. If a patient is initially randomized to receive placebo, and their study doctor confirms that they have had a return of active Crohn's Disease symptoms, they can receive infliximab. If a patient is initially randomized to receive infliximab, and their study doctor confirms that they are experiencing symptoms of Crohn's Disease, they may receive an increase in their infliximab dose. Infusions will be administered at Week 0 and then every 8 weeks thereafter through Week 200. The study will use a measure of Crohn's Disease activity that will be evaluated at each visit and at any time the patient has symptoms suggestive of their disease getting worse in order to capture recurrence. During the study, patients who meet the study definition of clinical recurrence will be eligible to have a blinded infliximab dose increase of 5 mg/kg. In other words, patients receiving placebo would receive infliximab 5 mg/kg, and patients receiving infliximab 5 mg/kg would have a dose increase to 10 mg/kg. Approximately 175 sites will be utilized, and approximately 290 patients will be enrolled. The interval between the first and last dose of study agent is 200 weeks. The planned duration of study participation is a maximum of 209 weeks (with a 1-week screening period, a 200-week treatment period, and a final study visit at Week 208). Group I (infliximab infusions): infliximab (5 mg/kg) will be administered by intravenous (IV) infusion at Week 0 and every 8 weeks thereafter through Week 200. Group II (placebo infusions): placebo will be administered by IV infusion at Week 0 and every 8 weeks thereafter through Week 200
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Crohn's Disease, Inflammatory Bowel Disease, infliximab, TNF-alpha
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
297 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Infliximab
Arm Type
Experimental
Arm Description
Infliximab Type=equal unit=mg number=5 form=intravenous infusion route=intravenous use once every 8 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo Type=equal unit=mg number=5 form=intravenous infusion route=intravenous use once every 8 weeks
Intervention Type
Biological
Intervention Name(s)
Infliximab
Intervention Description
Type=equal, unit=mg, number=5, form=intravenous infusion, route=intravenous use, once every 8 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Type=equal, unit=mg, number=5, form=intravenous infusion, route=intravenous use, once every 8 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 76
Description
CR criteria:1) A >=70-point increase from baseline in CDAI score [in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities];2)A CDAI score >=200;3)Evidence of endoscopic recurrence [ileal Rutgeerts score of >=i2 at anastomotic site or its equivalent elsewhere in GI tract] and 4)A negative stool test for C. difficile toxin (if, in the opinion of the investigator, the participant's symptoms are predominantly diarrheal); or at least 1 of followings:1) developing a new draining external fistula;2)re-opening and draining of a previously existing external fistula;3)developing a new internal fistula;4)developing a new perianal abscess or 5)developing a new intra-abdominal abscess more than 3 months after date of index surgery. In addition, participants who had a treatment failure [initiated a prohibited CD medication, had prohibited use of CD medication, or had surgery for CD] before or at Week 76 were considered to have clinical recurrence.
Time Frame
Baseline up to Week 76
Secondary Outcome Measure Information:
Title
Percentage of Participants With Endoscopic Recurrence of CD Prior to or at Week 76
Description
Endoscopic recurrence is defined as an ileal Rutgeert's score of >= i2 either at the anastomotic site or elsewhere in the gastrointestinal tract. In addition, participants who had a treatment failure (initiated a prohibited CD medication, had a prohibited use of a CD medication, or had a surgery for CD) prior to Week 76, and who developed a new draining external fistula or re-opening and draining of a previously existing external fistula or developed a new internal fistula, new perianal abscess or new intra-abdominal abscess more than 3 months after the date of the index surgery were considered to have had endoscopic recurrence prior to or at Week 76.
Time Frame
Baseline up to Week 76
Title
Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 104
Description
CR criteria:1) A >=70-point increase from baseline in CDAI score [in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities];2)A CDAI score >=200;3)Evidence of endoscopic recurrence [ileal Rutgeerts score of >=i2 at anastomotic site or its equivalent elsewhere in GI tract] and 4)A negative stool test for C. difficile toxin (if, in the opinion of the investigator, the participant's symptoms are predominantly diarrheal); or at least 1 of followings:1) developing a new draining external fistula;2)re-opening and draining of a previously existing external fistula;3)developing a new internal fistula;4)developing a new perianal abscess or 5)developing a new intra-abdominal abscess more than 3 months after date of index surgery. In addition, participants who had a treatment failure [initiated a prohibited CD medication, had prohibited use of CD medication, or had surgery for CD]before or at Week 104 were considered to have clinical recurrence.
Time Frame
Baseline up to Week 104
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a documented diagnosis of CD confirmed by endoscopic, histologic and/or radiologic studies prior to resection or by tissue obtained at resection
Have undergone an ileocolonic surgical resection
Patients must also be at an increased risk of recurrence of active CD
Patients must not have previously discontinued infliximab as a result of tolerability issues or they must be naive to treatment with infliximab. Provided patients meet the above criteria pertaining to infliximab, they are eligible to enroll if they received prior treatment with adalimumab and/or certolizumab
Patients must undergo screening for HBV
Baseline CDAI < 200
Have adequate blood and liver test values
Exclusion Criteria:
Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening
Have a chest radiograph within 3 months prior to the first infusion of study agent that shows a clinically significant abnormality, such as a malignancy or infection, or any abnormalities suggestive of TB
Have macroscopically active CD which was not resected at the time of surgery
Do not meet the criteria for being at an increased risk of postoperative recurrence of active CD as outlined in the inclusion criteria
Have evidence of an active infection at the time of randomization or have had a serious infection not related to CD (e.g., hepatitis, pneumonia, or pyelonephritis), within 6 months prior to screening
Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening
Have any known malignancy or history of malignancy within the 5-year period prior to screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence)
Have any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Biotech Inc. Clinical Trial
Organizational Affiliation
Janssen Biotech, Inc.
Official's Role
Study Director
Facility Information:
City
Birmingham
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Alabama
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United States
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La Jolla
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California
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United States
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Orange
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Redwood City
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San Diego
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Littleton
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Glastonbury
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Middletown
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New Haven
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Gainesville
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Jacksonville
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Miami
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Naples
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Weston
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Winter Park
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Decatur
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Macon
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Chicago
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Indianapolis
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Clive
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Iowa City
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Lexington
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Louisville
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Baton Rouge
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New Orleans
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Baltimore
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Chevy Chase
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Towson
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Boston
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Ann Arbor
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Troy
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Plymouth
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Rochester
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Lebanon
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Morristown
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Great Neck
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New York
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New York
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Rochester
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Asheville
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Chapel Hill
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Charlotte
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Durham
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Raleigh
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Cincinnati
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Cleveland
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Oklahoma City
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Oklahoma
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Portland
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Pittsburgh
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Germantown
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Nashville
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Grapevine
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Houston
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Plano
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San Antonio
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Salt Lake City
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Burlington
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Charlottesville
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Virginia
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Richmond
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Seattle
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Tacoma
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Madison
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Adelaide
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Australia
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Brisbane
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Australia
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Fremantle
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Australia
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Herston
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Malvern
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Australia
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Nambour
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Australia
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Graz
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Austria
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Salzburg
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Austria
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Wien
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Austria
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Bonheiden
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Belgium
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Brussels
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Belgium
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Brussel
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Belgium
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Roeselare
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Belgium
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Calgary
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Alberta
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Canada
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Edmonton
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Alberta
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Canada
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Vancouver
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British Columbia
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Canada
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Brandon
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Manitoba
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Canada
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Winnipeg
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Manitoba
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Canada
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Halifax
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Nova Scotia
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Canada
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Guelph
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Ontario
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Canada
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Kingston
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Ontario
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Canada
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London
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Ontario
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Canada
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Levis
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Quebec
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Canada
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Montreal
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Quebec
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Canada
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Quebec
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Canada
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Litomerice
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Czech Republic
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Prague
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Czech Republic
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Praha 7
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Czech Republic
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Bordeaux
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France
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Caen
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France
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Grenoble
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France
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Lille
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France
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Marseille
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France
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Nantes
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France
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Nice
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France
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Paris
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France
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Pessac
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France
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Rouen
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France
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Vandoeuvre Les Nancy
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France
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Berlin
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Germany
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Erlangen
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Herne
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Germany
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Kiel
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Germany
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Lÿneburg
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Germany
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Mannheim
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Germany
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München
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Germany
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Münster
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Germany
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Tübingen
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Germany
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Budapest
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Hungary
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Békéscsaba
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Hungary
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Debrecen
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Hungary
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Pecs N/A
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Hungary
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Israel
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Almere
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Netherlands
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Amsterdam Zuidoost
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Netherlands
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Amsterdam
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Netherlands
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Leiden
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Netherlands
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Maastricht
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Netherlands
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Rotterdam
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Netherlands
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Auckland
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New Zealand
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Christchurch
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New Zealand
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Dunedin
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New Zealand
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Hamilton
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New Zealand
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Wellington
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New Zealand
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Lodz
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Poland
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Warszawa
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Poland
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Wroclaw
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Poland
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Cambridge
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United Kingdom
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Cardiff
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Norwich
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United Kingdom
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Nottinghamshirecc
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United Kingdom
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Oxford
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26946343
Citation
Regueiro M, Feagan BG, Zou B, Johanns J, Blank MA, Chevrier M, Plevy S, Popp J, Cornillie FJ, Lukas M, Danese S, Gionchetti P, Hanauer SB, Reinisch W, Sandborn WJ, Sorrentino D, Rutgeerts P; PREVENT Study Group. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection. Gastroenterology. 2016 Jun;150(7):1568-1578. doi: 10.1053/j.gastro.2016.02.072. Epub 2016 Mar 3.
Results Reference
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Learn more about this trial
A Multicenter Trial Comparing REMICADE (Infliximab) and Placebo in the Prevention of Recurrence in Crohn's Disease (CD) Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence
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