Clinical Trials Register

Summary
EudraCT Number:	2017-001737-85
Sponsor's Protocol Code Number:	80-84800-98-81014
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-04-03
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2017-001737-85

A.3

Full title of the trial

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

Effectiviteit van albendazol voor het induceren van mucosale heling bij patiënten met de ziekte van Crohn en onder behandeling met anti-TNF monotherapie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Effectiviteit van albendazol voor het induceren van mucosale heling bij patiënten met de ziekte van Crohn en onder behandeling met anti-TNF monotherapi

A.3.2

Name or abbreviated title of the trial where available

ADD UP

A.4.1

Sponsor's protocol code number

80-84800-98-81014

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	academic medical centre
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMW
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Academic Medical Centre
B.5.2	Functional name of contact point	Geert D'Haens
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 9
B.5.3.2	Town/ city	Amsterdam
B.5.3.4	Country	Netherlands
B.5.6	E-mail	g.dhaens@amc.uva.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	albendazole (Eskazole)
D.2.1.1.2	Name of the Marketing Authorisation holder	glaxosmithkline
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	albendazole
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	antihelmintic agent

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Crohn's disease

Ziekte van Crohn

E.1.1.1

Medical condition in easily understood language

Crohn's disease

ziekte van Crohn

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10013099
E.1.2	Term	Disease Crohns
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

Secondary objective is to conduct a cost-effectiveness and cost-utility analysis and a budget impact analysis of anti-TNF and albendazol combination therapy.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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, γ-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

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 12

E.5.2

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

E.5.2.1

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)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

110

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

According to current treatment guidelines

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-03-01

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