crohn's disease
Conditions
Interventions
Group I: Infliximab Infusions
Infliximab (equivalent to 5 mg/kg) will be administered by IV infusion at Week
0 and every 8 weeks thereafter through Week 200
Group II: Placebo Infusions
Placebo will
Sponsors
Janssen Biologics BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Man or woman 18 years of age or older;2. Are considered eligible according to the following TB screening criteria: a. Have no history of latent or active TB prior to screening. An exception is made for patients with a history of latent TB and documentation of having completed appropriate treatment for latent TB (see Section 9.1.2) within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation. b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. c. Have no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent. d. Within 6 weeks prior to the first administration of study agent, have a negative QuantiFERON-TB Gold test result (see Attachment 1.1), or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB (see Section 9.1.2) has been initiated either prior to or simultaneously with the first administration of study agent. A negative tuberculin skin test (see Attachment 1.2) or a newly identified positive tuberculin skin test result during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent is considered acceptable if the QuantiFERON-TB Gold test is not acceptable in that country. e. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.;3. Have a documented diagnosis of CD confirmed by endoscopic, histologic, and/or radiologic studies prior to resection or by tissue obtained at resection.;4. Have undergone an ileocolonic surgical resection (i.e. an intestinal resection with an ileocolonic anastomosis). Patients who have undergone an intestinal resection with an end or loop ileostomy (the "qualifying surgery") within the last year are also eligible if they have now undergone an operation to close the ileostomy and resume intestinal continuity by construction of an ileocolonic anastomosis. In this case, the time parameters for eligibility refer to the time after the re-anastomosis surgery. In addition, patients must: a. Have no evidence of macroscopic CD at the close of surgery according to the surgeon b. Have no known active CD anywhere else in the GI tract, including the findings at surgery c. Be able to undergo randomization no later than 45 days after surgery Patients will not be eligible for the study if the qualifying surgery was their first in > 10 years since their diagnosis of CD and was performed for fibrostenotic stricturing disease involving < 10 cm of the intestine. [Note: In the case of a patient undergoing re-anastomosis surgery, "qualifying surgery" refers to the operation prior with intestinal resection and construction of the ileostomy.];5. Patients must also be at an increased risk of recurrence of active CD, as defined by at l
Exclusion criteria
Exclusion criteria: 1. Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criterion 2 for information regarding eligibility with a history of latent TB.;2. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.;3. 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.;4. Have had a nontuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.;5. Have initial and repeat indeterminate QuantiFERON-TB Gold test results.;6. Are considered ineligible according to the TB eligibility assessment, screening and early detection of reactivation rules (see Section 9.1.2).;7. Have macroscopically active CD which was not resected at the time of surgery.;8. Have had any active perianal disease within 3 months of screening (except skin tags) or have had any draining fistula within 3 months of screening unless the fistula was removed at the index surgery.;9. Have evidence of active CD in regions beyond the site of surgery in the GI tract within 1 year of the time of enrollment.;10. Do not meet the criteria for being at an increased risk of postoperative recurrence of active CD as outlined in the inclusion criteria.;11. Had, in association with their most recent intra-abdominal surgery, postoperative complications such as, but not limited to, postoperative intra-abdominal abscess, wound dehiscense, anastomotic leak, the need for a second operation, pulmonary embolus, or serious infection.;12. Have documented short bowel syndrome (more than 100 cm in total of small bowel resected).;13. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.;14. Have shown a previous immediate hypersensitivity response, including anaphylaxis, to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody).;15. Have a known allergy to murine proteins or other chimeric proteins.;16. Have received within 3 months prior to screening or are expected to receive any live viral (e.g., small-pox) or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent.;17. 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.;18. Have had a Clostridium difficile (C. difficile) infection within the past 4 months.;19. 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.;20. Have current active hepatitis B (including chronic active hepatitis B or asymptomatic carrier state [hepatitis B surface antigen positive; HBsAg-positive]) or a history of hepatitis C infection.;21. Have documented or suspected human immunodeficiency virus (HIV) infection.;22. Have current signs or symptoms of or a history of systemic lupus erythematosus; severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases.;23. Have a transplanted organ (with the exception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is clinical recurrence of CD through Week 76. Clinical recurrence is a composite endpoint defined by the following: • A >= 70-point increase from baseline in CDAI score; and • A CDAI score >= 200; and • Evidence of endoscopic recurrence. Endoscopic recurrence is defined as a Rutgeerts score of >= i2 at the anastomotic site or its equivalent elsewhere in the GI tract. • If in the opinion of the investigator, the patient's symptoms are predominantly diarrheal, a negative stool test for C. difficile must be present to confirm the true CD nature of the flare. or • Developing a new draining external fistula. or • Re-opening and draining of a previously existing external fistula. or • Developing a new internal fistula. or • Developing a new perianal abscess. or • Developing a new intra-abdominal abscess more than three months after the date of the index surgery. Note that "baseline" CDAI refers to the CDAI collected during the screening period that qualified the patient for the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| The major secondary efficacy endpoint is endoscopic recurrence of CD through Week 76. | — |
Countries
Netherlands
Outcome results
None listed