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

INTERVENTION: Trade Name: albendazole (Eskazole) Product Name: albendazole Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Crohn's disease ; MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856 Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: In the current project the main objective is to evaluate the efficacy and safety of the addition of albendazole to anti‐TNF monotherapy (=4 months) in adult patients with Crohn’s disease with incomplete mucosal healing. Primary end point(s): 1. 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 Objective: Secondary objective is to conduct a cost‐effectiveness and cost‐utility analysis and a budget impact analysis of anti‐TNF and albendazol combination therapy. Timepoint(s) of evaluation of this end point: At week 12 SECONDARY OUTCOME: Secondary end point(s): 1. 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; 2. 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; 3. Costs per Quality Adjusted Life year (QALY); 4. Clinical endpoints:; 4.1. Change in CDAI from baseline to W12; 4.1.1. Clinical remission: CDAI < 150; 4.1.2. Clinical (partial) response: decrease in CDAI = 70 points [CR‐70]); 4.2. General and change in quality of life, as measured by the IBDQ, SF‐36 and EQ‐5D‐5L at baseline, week 12 and 36; 4.3. 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; 4.4. Occurrence of (serious) adverse events (SAE); 5. Change in Anti‐TNF serum concentration and anti‐drug‐antibodies from baseline to W12; 6. Proportion of patients with hs‐CRP < 5mg/L at W12 ; 7. Proportion of patients with fecal calprotectin < 250 µg/g at W12; 8. Proportion of patients with fecal calprotectin <100 µg/g at W12 ; 9. 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).; 10. Presence of type 2 regulatory wound‐healing macrophages (CD14+CD68+CD206+) by immunohistochemical staining and fluorescence‐activated cell sorting on intestinal biopsies; Timepoint(s) of evaluation of this end point: Different timepoints during the 9 months duration of the trial (Week 0, 2, 4, 8, 12 and 36) INCLUSION CRITERIA: 1. Patients =18 years and =65 years 2. Diagnosis of CD, based on endoscopy and histopathologic examination of mucosal biopsies 3. Written informed consent 4. 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 5. 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. 6. 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. 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 subje