E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Luminal Crohn's disease patients in steroid free remission for at least 6 months and on combination therapy with infliximab and antimetabolites for at least 1 year |
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E.1.1.1 | Medical condition in easily understood language |
Luminal Crohn's disease patients in steroid free remission for at least 6 months and on combination therapy with infliximab and antimetabolites for at least 1 year |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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 |
To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior (better) to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior (not any worse) with regards to the mean time spent in remission over the same duration |
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E.2.2 | Secondary objectives of the trial |
- To identify baseline predictive factors of relapse in the three study groups. - To assess the ability of blood C-reactive protein (CRP) and fecal calprotectin to predict short term relapse in the three groups. - To assess time spent in clinical remission in the three groups. - To assess the rate of treatment failure in the three study groups. - To assess the time to treatment failure in the three study groups. - To assess progression of bowel damage in the three groups. - To assess the safety and efficacy of infliximab retreatment in the antimetabolites group. - To assess safety in the three study groups. - To assess the health related quality of life in the three study groups. - To assess direct and indirect costs in the three study groups. - To assess evolution of blood CRP and fecal calprotectin in the three study groups. - To assess evolution of infliximab trough levels and antibodies to infliximab (ATI) in the two infliximab scheduled maintenance groups. - To assess |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of Crohn’s disease. - Male or female, age > 18 years. - Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn’s disease. - Combined therapy with scheduled infliximab and anti-metabolites for at least 12 months. - Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 6 months. - Antimetabolites administered at a stable dosage for the last 6 months: at least 1 mg/Kg or 2 mg/Kg for mercaptopurine and azathioprine, respectively, or the highest tolerated dosage if intolerance to standard dose; at least 15 mg/week subcutaneously for methotrexate. - Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients’ files. - CDAI < 150 at baseline. - A contraceptive during the whole study - Patients able to understand the information provided to them and to give written informed consent for the study |
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E.4 | Principal exclusion criteria |
- Patients who have presented a severe acute or delayed reaction to infliximab. - Perianal fistulae as the main indication for infliximab treatment - Active perianal/abdominal fistulae at time of inclusion, defined by active drainage - Patients with ostomy or ileoanal pouch - Pregnancy or planned pregnancy during the study - Inability to follow study procedures as judged by the investigator - Non-compliant subjects. - Participation in another therapeutic study |
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E.5 End points |
E.5.1 | Primary end point(s) |
There are two co-primary efficacy end points:
Relapse rate at 2 years, relapse being defined by either one of the following events: - A CDAI>250 at any visit or between 150 and 250 with an increase of at least 70 points, over two consecutive visits one week apart associated with a CRP > 5 mg/l or a fecal calprotectin > 250 microg/g - A new opening fistula, perianal or entero-cutaneous. - An intra-abdominal abcess (size of at least 3 cm) or perianal abcess (size of at least 2 cm) - An episode of intestinal obstruction due to Crohn’s lesions confirmed by medical imaging and requiring hospitalisation (also considered as treatment failure, see below)
Mean restricted time spent in remission This time will be computed in all patients, from baseline (CDAI <150 and with absence of fistula drainage) until relapse, as defined above, within the 2 first years. First and subsequent remissions will be summed up within the two first years.
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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) |
- To identify baseline predictive factors of relapse in the three study groups. - To assess the ability of blood CRP and fecal calprotectin to predict short term relapse in the three groups. - To assess time spent inclinical remission in the three groups. - To assess the rate of treatment failure in the three study groups. - To assess the time to treatment failure in the three study groups. - To assess progression of bowel damage in the three groups. - To assess the safety and efficacy of infliximab retreatment in the antimetabolites group. - To assess safety in the three study groups. - To assess the health related quality of life in the three study groups. - To assess direct and indirect costs in the three study groups. - To assess evolution of blood CRP and fecal calprotectin in the three study groups. - To assess evolution of infliximab trough levels and ATI in the two infliximab scheduled maintenance groups. - To assess genetic association with the various clinical and biological outcomes. - To assess the impact of 6TGN levels on the various clinical and biological outcomes in the purine treated patients
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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 | 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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
Combination therapy versus monotherapy with either infliximab or antimetabolites |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 33 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 may be stopped prematurely should the independent Data Monitoring and Safety Committee identify major concerns regarding study conduct or data quality and recommend that this action be taken. Otherwise the end of trial will be classed as the last patient's last visit. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |