Crohn's disease MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856
Conditions
Interventions
Trade Name: albendazole (Eskazole)
Product Name: albendazole
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
academic medical centre
Eligibility
Sex/Gender
All
Inclusion criteria
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 subjects for this age range 110 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Ulcerative colitis or indeterminate colitis 2. Current malignancy 3. Women: current pregnancy wish, pregnancy or lactation. Men: active child wish 4. Ongoing use of an immunomodulator (including azathioprine, methotrexate, 6-thioguanine, 6 mercaptopurine or mycophenolic acid). 5. Prior failure on anti-TNF and immunomodulator combination therapy due to refractory disease per treating physicians opinion. 6. Elevated liver enzymes (ALAT, ASAT, LDH, ?-GT, AF) >1.5 times the upper limit of normal (ULN) 7. Current use of any CYP3A4 inducing or inhibiting agents 8. Patients on prednisone >10mg/day or budesonide >6mg/day 9. Patients who require rescue therapy with corticosteroids during the screening phase 10. Leukopenia (neutrophil count < 1.8x10^9/L) and/or thrombopenia <50 x 10^9/L 11. Other conditions which in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;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.;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;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Netherlands
Contacts
Public ContactGeert D'Haens
Academic Medical Centre
Outcome results
None listed