Clinical trial NCT01190839: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Inflammatory Bowel Disease
infliximab
TNF-alpha
Lead sponsor: Janssen Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-08-30
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Primary outcomes:
measure: Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 76
timeFrame: Baseline up to Week 76
Secondary outcomes:
measure: Percentage of Participants With Endoscopic Recurrence of CD Prior to or at Week 76
timeFrame: Baseline up to Week 76
measure: Percentage of Participants With Clinical Recurrence (CR) of Crohn's Disease (CD) Prior to or at Week 104
timeFrame: Baseline up to Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
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state: California
city: Orange
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state: California
city: Redwood City
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state: California
city: San Diego
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state: Colorado
city: Glastonbury
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state: Connecticut
city: Middletown
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state: Connecticut
city: New Haven
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state: Connecticut
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state: Florida
city: Jacksonville
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city: Miami
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city: Naples
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city: Winter Park
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state: Georgia
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state: Illinois
city: Indianapolis
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city: Clive
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state: Iowa
city: Iowa City
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state: Kentucky
city: Baton Rouge
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state: Louisiana
city: New Orleans
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state: Louisiana
city: Baltimore
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state: Maryland
city: Chevy Chase
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city: Lees Summit
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state: Missouri
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city: Morristown
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state: New Jersey
city: Great Neck
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city: Rochester
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city: Asheville
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state: North Carolina
city: Chapel Hill
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city: Durham
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country: Austria
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country: Austria
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country: Belgium
city: Brussels
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city: Brussel
country: Belgium
city: Gent
country: Belgium
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city: Liege
country: Belgium
city: Roeselare
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
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city: Vancouver
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state: British Columbia
city: Brandon
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state: Manitoba
city: Winnipeg
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state: Manitoba
city: Halifax
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state: Nova Scotia
city: Guelph
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Levis
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Litomerice
country: Czech Republic
city: Prague
country: Czech Republic
city: Praha 7
country: Czech Republic
city: Bordeaux
country: France
city: Caen
country: France
city: Grenoble
country: France
city: Lille
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Nice
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city: Paris
country: France
city: Pessac
country: France
city: Rouen
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Kiel
country: Germany
city: Lÿneburg
country: Germany
city: Mannheim
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Tübingen
country: Germany
city: Budapest
country: Hungary
city: Békéscsaba
country: Hungary
city: Debrecen
country: Hungary
city: Pecs N/A
country: Hungary
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Almere
country: Netherlands
city: Amsterdam Zuidoost
country: Netherlands
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Dunedin
country: New Zealand
city: Hamilton
country: New Zealand
city: Wellington
country: New Zealand
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Norwich
country: United Kingdom
city: Nottinghamshirecc
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
affiliation: Janssen Biotech, Inc.
name: Janssen Biotech Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
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.