Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease

Study Overview
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Brief Summary
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To investigate whether sustained trough levels of IFX can be achieved using IFX (Infliximab) trough level measurements and adjustment of dosing based upon these levels by means of two different standardized algorithms in comparison with 'standard of care' IFX treatment and its effects on clinical and endoscopic outcomes.

Official Title
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A Randomized Controlled Trial Investigating Tailored Treatment With Infliximab for Active Luminal Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Infliximab
* Drug: Infliximab
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Active CD (CDAI>220) and signs of active inflammation as evidenced by elevated serum hsCRP levels (>5 mg/L) and/or elevated fecal calprotectin levels (>250 µg/g) and endoscopically visible ulcers. Patients must be naïve to biologics with indication for starting anti-TNF therapy in accordance with national reimbursement criteria. Patients must be naïve to thiopurines or have failed therapy with thiopurines (in which case AZA will be continued). Ongoing steroids are allowed if at stable dose for at least 2 weeks and at a maximum of prednisone 40 mg/d or budesonide 9 mg/day. Patients who consent to receiving Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with azathioprine (2,5 mg/kg/day). Patients who develop AZA intolerance during the trial are continued in the trial without AZA (ie IFX monotherapy). Exclusion Criteria: Absence of endoscopically visible ulcers Prior exposure to infliximab (other biologics allowed) Ongoing steroid therapy at doses > 40 mg/d prednisolone equivalent Previous intolerance to azathioprine leading to drug discontinuation Ongoing infections Positive tuberculosis screen per local guidelines Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer Indication for immediate surgery Pregnant or breast-feeding woman. Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools Active tuberculosis Untreated latent tuberculosis (see national recommendations. Appendix 2). Non-compliant subjects. Participation in another therapeutic study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1 =Control Group<br>the dose of IFX will be increased by 5 mg/kg (maximally 1 time) based on symptom relapse (usual clinical practice) Dose will be kept stable ofr the rest of the trial Dose decreases will not be allowed. | Drug: Infliximab<br>* Perfusion of IFX 5mg/kg to be increased to 10 mg/kg based on clinical symptoms<br>* Other names: IFX;|
| Active Comparator: Cohort 2<br>Dose of IFX will be increased by 2.5 mg/kg (maximally 2 times) if the following criteria are met A dose increase is maintained for the following infusions | Drug: Infliximab<br>* Perfusion of IFX 5mg/kg or 10 mg/kg if dose increase criteria are met (biological)<br>* Other names: IFX;|
| Active Comparator: Cohort 3<br>Dose of IFX will be increased by 5 mg/kg (maximally 1 time) if the following criteria are met A dose increase is maintained for the following infusions | Drug: Infliximab<br>* Perfusion of IFX 5mg/kg or 7,5 mg/kg if dose increase criteria are met (biological)and 10mg/kg if dose increase criteria are met for a second time<br>* Other names: IFX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of remission | Proportion of patients with steroid-free remission (CDAI < 150) and endoscopic healing (absence of ulcers) at week 54 CDAI = Crohn's Disease Activity Index | 54 weeks after Inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission | Clinical remission (CDAI <150) at each visit and the whole study period | week 14 after inclusion | 
| Endoscopic evaluation | percentage of patients in each group with absence of ulcers; percentage of patients in each group with >50% improvement in CDEIS (Crohn's Disease Endoscopic Index Score | week 0, week 12 and week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, IFX trough level