| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
|
| 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 prinicipal aim of this study is to investigate the effect of infliximab on the transmural Inflammatory component and the fibrous lesions in the distal small bowel in patients with Crohn’s disease, based on serial MRI. This is a diagnostic, observational trial.
The primary endpoint of this study is the number of patients achieving a clinically significant change in MRI enteroclysis inflammatory sub-scores of severity in Ileal Crohn’s Disease (MICD); this is defined as an improvement of at least 2 points and at least 50% on the inflammatory subscores. i.e. 4 to 2 or 5 to 2 or 8 to 4 (subscores defined in section 19), as measured with contrast enhanced MRI enteroclysis at week 26 compared to baseline |
|
| E.2.2 | Secondary objectives of the trial |
Secondary endpoints include:
1) Changes in the overall MICD score at week 2 and week 26 compared to baseline
2) Changes in the individual MICD inflammatory subscores (wall thickening, contrast enhancement and extramural involvement) at week 2 and week 26 compared to baseline.
3) Changes in the individual MICD criteria for obstructive disease (intrastenotic luminal diameter and prestenotic dilation) at week 2 and week 26 compared to baseline.
4) Number of patients reaching CDAI remission (< 150) or CDAI response criteria (a drop of 100 points) at every visit (except week 30).
5) Correlation between the MICD total score and CDAI at baseline, week 2 and 26
6) Correlation between different MICD inflammatory subscores and CDAI at baseline, week 2 and 26
7) Correlation between the different MICD criteria for obstructive disease and CDAI at baseline, week 2 and 26
8) Changes in disease activity as measured with CDAI and Harvey Bradshaw questionnaire at every visit (except week 30).
9 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria:
To be eligible for the trial, patients must meet all of the following inclusion criteria:
1) Men and women ≥ 18 and ≤ 65 years of age,
2) Are capable of understanding and signing an informed consent
3) Are considered eligible according to the following tuberculosis (TB) screening criteria:
a) Have no history of latent or active TB prior to screening
b) Have no signs or symptoms suggestive of active TB upon medical history or physical examination
c) Have had no recent close contact with a person with active TB
d) Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of infliximab and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
4) The presence of active disease:
a) CDAI > 220
b) CRP > 5 mg/L (see amendment to protocol)
5) Strong Gadolinium (Gd) uptake on baseline contrast enhanced MRI enteroclysis (see MRI manual)
6) Ileal wall thickening of > 4 mm on baseline contrast enhanced MRI enteroclysis
7) Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last medication
Exclusion Criteria:
Patients who meet any of the following criteria may not be enrolled in the study:
1) Have a medical contraindication for MRI enteroclysis (eg metal implants, including metal prosthetic heart valve(s), implantable devices, including a cardiac pacemaker and severe claustrophobia)
2) use more than 15 mg of oral steroids (prednisone or equivalent) within the 2 weeks prior to baseline MRI. IV use of steroids is not allowed within that same period
3) Have a severe prestenotic dilation of the ileum on screening MRI (severe dilation is defined as > 2 times the luminal diameter of the unaffected ileum)
4) Have had bowel resection of > 100 cm
5) Have presence of an abdominal abscess
6) Have MRI enteroclysis confirmed internal fistula
7) Be considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section on: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation Rules (refer to sections 5.9 and 18).
8) Have Screening laboratory test results as follows:
a) White blood cells (WBCs) < 3.0 x 109 cells/L
b) Platelets < 100 X 109 cells/L
c) Serum creatinine > 132 μmol/L (> 1,5 mg/dL)
d) Serum transaminase levels exceeding 2 times the upper limit of normal for the site laboratory
9) Have had any previous treatment with monoclonal antibodies or antibody fragments
10) Have a history of receiving human/murine recombinant products or a known allergy to murine products
11) Have documentation of seropositivity for human immunodeficiency virus (HIV)
12) Have a positive test for hepatitis B surface antigen or hepatitis C
13) History of alcohol or substance abuse in the 6 months prior to the study
14) Have a known history of serious infections (eg, hepatitis, pneumonia, or pyelonephritis) in the previous 3 months
15) Have a known history of a demyelinating disease, such as multiple sclerosis
16) Have or have had an opportunistic infection (eg, herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
17) Have a chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg. bronchiectasis), sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer
18) Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly
19) Currently have any known malignancy or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence
20) Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease
21) Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access
22) Use any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer
23) Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)
24) Have a concomitant diagnosis or history of congestive heart failur |
|
| E.4 | Principal exclusion criteria |
Ssee E3
Significant prestenotic dilatation of the ileum on baseline MRI scan
Previous resection of more than 100cm bowel
Presence of abdominal abscess |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the number of patients achieving a clinically significant change in MRI enteroclysis score of severity in Ileal Crohn’s Disease (MICD); defined as an improvement of at least 2 points and at least 50% on the inflammatory subscores. i.e. 4 to 2 or 5 to 2 or 8 to 4, as measured with contrast enhanced MRI enteroclysis at week 26 compared to baseline |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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