Crohn's disease
Conditions
Interventions
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 f
Sponsors
Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Eligibility
Inclusion criteria
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.
Exclusion criteria
Exclusion criteria: • Ulcerative colitis or indeterminate colitis • Current malignancy • Women: current pregnancy wish, pregnancy or lactation. Men: active child wish • Ongoing use of an immunomodulator (including azathioprine, methotrexate, 6-thioguanine, 6 mercaptopurine or mycophenolic acid). • Prior failure on anti-TNF and immunomodulator combination therapy due to refractory disease per treating physicians opinion. o NOTE: Patients with prior use of co-therapy who stopped the IMM due to stable disease (with continued anti-TNF treatment), prior IMM monotherapy and prior intolerance to IMM’s are considered eligible for enrolment • Elevated liver enzymes (ALAT, ASAT, LDH, γ-GT, AF) >1.5 times the upper limit of normal (ULN) • Current use of any CYP3A4 inducing or inhibiting agents (outlined in table 1, section 5.3, page 18) • Patients on prednisone >10mg/day or budesonide >6mg/day • Patients who require rescue therapy with corticosteroids during the screening phase • Leukopenia (neutrophil count < 1.8x10^9/L) and/or thrombopenia <50 x 10^9/L • 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 |
|---|---|
| •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
| Measure | Time frame |
|---|---|
| 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 | — |
Contacts
Public ContactToer W. Stevens
Academic Medical Center Amsterdam, Department of gastroenterology and hepatology, C2-231
Outcome results
None listed