E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Crohn's disease with absence of disease activity during biologic therapy (infliximab) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with inflammatory bowel disease (Crohn's disease) with absence of disease activity during treatment with a biologic agent. |
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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 | 20.0 |
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 |
The aim of the study is to investigate if infliximab (IFX) can safely and favourably be discontinued in patients with Crohn's disease in sustained complete remission on IFX maintenance therapy. |
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E.2.2 | Secondary objectives of the trial |
Further we will examine the clinical utility of measuring levels/activity of IFX and activity of anti-IFX Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of IFX therapy. Additional, we will investigate the optimal time-point, out of three, to measure this activity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Primary inclusion criteria:
• Luminal Crohn's disease defined according to standardized diagnostic criteria.
• Age ≥ 18 years.
• IFX treatment length minimum 12 months (minimum 365 days from first IFX administration to last IFX administration prior to inclusion). Episodic therapy with IFX pause > 12 weeks is not accepted within the last year. The treatment interval in the last three months has to be of 6-10 weeks.
• Complete remission defined as:
o Crohn’s Disease Activity Index (CDAI) score < 150,22 and
o Biochemical remission, and
o No other signs of disease activity as evaluated by endoscopic examination, capsule endoscopy or by magnetic resonance imaging (MRI).
• Stable remission, judged by the treating physician, at two consecutive treatments visits corresponding 2 scheduled IFX infusions. Thus, the first visit is during IFX maintaining therapy (screening visit). The second visit is at time of inclusion corresponding time of next scheduled IFX infusion (i.e. after ≈ 8 weeks).
• No use of oral steroids within 3 months prior to inclusion.
• Concomitant therapy with other immune suppressants, except steroids, is allowed. The dosage and frequency must have been stable three months prior to inclusion and must remain stable throughout the study period.
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E.4 | Principal exclusion criteria |
Primary exclusion criteria:
• Initial indication for IFX being predominantly fistulizing perianal disease.
• Active fistulizing perianal disease.
• Any contraindications for continuing IFX treatment, including prior acute or delayed infusion reaction to a TNF- inhibiting agent, any active infection requiring parenteral or oral antibiotic treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
• Any condition including physician finds incompatible with participation in the study or the patient being unwilling or unable to follow protocol requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint
The primary endpoint of this study is the proportion of patients who maintain remission, i.e. CDAI <150.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This endpoint is assessed at 48 weeks. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints
Patients who continue IFX and patients who discontinue IFX are compared with respect to the following at 48 weeks after inclusion:
• Proportion of patients who maintain complete remission.
• Proportion of patients experiencing relapse.
• The proportion of patients, who are no longer in remission, but are not in relapse.
• Median time to relapse after discontinuation of IFX.
• Change from baseline in disease activity evaluated by: CDAI as assessed by CDAI score, quality of life (QoL) as assessed by short-IBDQ, work productivity and activity as assessed by WPAI, biochemical markers assessed by, i.e. C-reactive protein (CRP), platelets, white blood cell (WBC) count, Hemoglobin (Hb) and fecal calprotectin and colonoscopy (scored by the SES-CD) / MR imaging.
• Economical expenses in the to groups. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints are assessed at 48 weeks |
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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 | 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) | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |