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

• Register: EUCTR
• Last refreshed on: 6 July 2020
• Main ID: EUCTR2017-001737-85-NL
• Date of registration: 03/04/2018
• Prospective Registration: Yes
• Primary sponsor: academic medical centre
• Public title: Efficacy of AlbenDazole to inDuce mUcosal healing in Patients with Crohn's disease on anti-TNF monotherapy
• Scientific title: Efficacy of AlbenDazole to inDuce mUcosal healing in Patients with Crohn's disease on anti-TNF monotherapy - ADD UP
• Date of first enrolment: 17/07/2018
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001737-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Geert D'Haens
• Affiliation: Academic Medical Centre

• Name: Geert D'Haens
• Affiliation: Academic Medical Centre

Key inclusion & exclusion 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:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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]

Intervention(s)

Trade Name: albendazole (Eskazole)
Product Name: albendazole
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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(s)

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)

Secondary ID(s)

80-84800-98-81014

Source(s) of Monetary Support

ZonMW

Ethics review

Status: Approved
Approval date: 17/07/2018
Contact: