E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study will be to compare the efficacy of infliximab with that of placebo in the prevention of clinical recurrence of CD through Week 76, defined as a composite endpoint that requires endoscopic confirmation of recurrence, in patients who are at an increased risk of active CD recurrence following ileocolonic resection. |
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E.2.2 | Secondary objectives of the trial |
The major secondary objective will be to compare the efficacy of infliximab with that of placebo in the prevention of endoscopic recurrence of CD through Week 76, defined as a Rutgeerts score ≥ i2 either at the anastomosis or elsewhere in the gastrointestinal [GI] tract, in patients who are at an increased risk of active CD recurrence following ileocolonic resection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is clinical recurrence of CD prior to or at 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 of ≥ 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; and • 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 3 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. Patients who meet the criteria for clinical recurrence at Week 76 or at any time point prior to Week 76 will be considered to have clinical recurrence through Week 76. Patients who initiate a prohibited CD-related medication or have a prohibited use of a CD medication prior to Week 76 will be considered to have had clinical recurrence. Patients who have surgery for CD prior to Week 76 will be considered to have had clinical recurrence. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Compare the efficacy of infliximab with that of placebo in the prevention of endoscopic recurrence of CD : Presence or absence of mucosal inflammation and ulceration will be evaluated via video ileocolonoscopy at Week 76, and to ensure that there is no recurrence of Crohn's Disease in the colon |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
France |
Italy |
Austria |
Netherlands |
New Zealand |
Australia |
Czech Republic |
Germany |
Hungary |
Israel |
Poland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study is considered completed with the last visit of the last patient participating in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |