Discontinuation of biologic therapy (infliximab) in patients with Crohn’s disease during sustained complete absence of disease activity: A Nordic multi-center, double blinded, randomized, placebo controlled study

Phase 1

Conditions: Patients with Crohn's disease with absence of disease activity during biologic therapy (infliximab)
MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2012-002702-51-DK

Lead Sponsor: Department of medical gastroenterology S, Odense University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 136

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:
oCrohn’s Disease Activity Index (CDAI) score < 150,22 and
oBiochemical remission, and
oNo 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. ;Secondary Objective: 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.;Primary end point(s): Primary endpoint<br><br>The primary endpoint of this study is the proportion of patients who maintain remission, i.e. CDAI <150.<br><br>;Timepoint(s) of evaluation of this end point: This endpoint is assessed at 48 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints<br><br>Patients who continue IFX and patients who discontinue IFX are compared with respect to the following at 48 weeks after inclusion:<br><br>•Proportion of patients who maintain complete remission. <br>•Proportion of patients experiencing relapse. <br>•The proportion of patients, who are no longer in remission, but are not in relapse. <br>•Median time to relapse after discontinuation of IFX.<br>•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.<br>•Economical expenses in the to groups.;Timepoint(s) of evaluation of this end point: Endpoints are assessed at 48 weeks

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