Efficacy of AlbenDazole to inDuce mUcosal healing in Patients with Crohn's disease on anti-TNF monotherapy: ADD UP

INTERVENTION: 110 subjects are randomly assigned to receive either albendazole or placebo (1:1) in combination with continued anti‐TNF treatment at unchanged dose. Patients will receive oral albendazole treatment for 12 weeks in a weight adjusted dosage or placebo CONDITION: Crohn's disease ; ; PRIMARY OUTCOME: • Proportion of patients with absence of ulcers on centrally read endoscopies after 12 weeks of albendazole and anti‐TNF combination treatment compared to placebo SECONDARY OUTCOME: Key secondary endpoints ; ; • Proportion of patients with endoscopic response on centrally read endoscopies defined as a reduction in the Simple Endoscopic Severity index (SES‐CD) score by = 50% compared to baseline ; ; • Proportion of patients with endoscopic remission on centrally read endoscopies defined as a SES‐CD score < 3 in general or < 2 in case of L1 (ileal) disease ; ; • Clinical endpoints: ; ; o Change in CDAI from baseline to W12 ; ; ? Clinical remission: CDAI < 150 ; ; ? Clinical (partial) response: decrease in CDAI = 70 points [CR‐70]) ; ; o General and change in quality of life, as measured by the IBDQ, SF‐12 and EQ‐5D‐5L at baseline, week 12 and 36 ; ; o Patient Reported Outcome Measure (PROM): assessment of the general and change in functional status and well‐being measured from the patients’ perspective by the IBD‐CONTROL questionnaire [25], at baseline, week 12 and 36 ; ; Other secondary endpoints ; ; • Change in Anti‐TNF serum concentration and anti‐drug‐antibodies from baseline to W12 ; ; • Proportion of patients with hs‐CRP < 5mg/L at W12 ; ; • Proportion of patients with fecal calprotectin < 250 µg/g at W12 ; ; • Proportion of patients with fecal calprotectin <100 µg/g at W12 ; ; • Change in Anti‐TNF serum concentration and anti‐drug‐antibodies from baseline to W12 ; ; • Histological changes from baseline to W12 based on centrally read scanned biopsies using the colonic and ileal global histologic disease activity scoring system (CGHAS/IGHAS, appendix 14.2) and the Robarts histology index (RHI, appendix 14.3). ; ; • Presence of type 2 regulatory wound‐healing macrophages (CD14+CD68+CD206+) by immunohistochemical staining and fluorescence‐activated cell sorting on intestinal biopsies ; ; • Occurrence of (serious) adverse events ; ; • Quality Adjusted Life Years (QALYs) ; ; • Costs ; ; • Identification of baseline predictive genetic marker for therapy response to albendazole ; INCLUSION CRITERIA: • Patients =18 years and =65 years • Diagnosis of CD, based on endoscopy and histopathologic examination of mucosal biopsies • Written informed consent • Active mucosal disease as defined by a repeated faecal calprotectine = 250 µg/g at 2 consecutive occasions (=2 weeks and =3 months interval) AND presence of mucosal lesions as defined by a SES‐CD > 6 (= 4 for L1 (ileal) disease) on screening ileocolonoscopy • On anti‐TNF therapy (ADM at a dose of 40mg Subcutaneous (SC) every week (QW) or every other week (Q2W) and IFX at a dose of 5‐10 mg/kg every 4‐8 weeks) for a period of at least 4 months at stable dose. • Therapeutic trough serum concentrations of anti‐TNF at screening (for IFX = 3 µg/ml and for adalimumab (ADM) = 5 µg/ml) and undetectable levels of anti‐drug antibodies (ADA’s) at baseline.