Clinical Trials Register

Summary
EudraCT Number:	2011-003038-14
Sponsor's Protocol Code Number:	2010-2
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-01-03
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-003038-14

A.3

Full title of the trial

A RANDOMIZED CONTROLLED TRIAL INVESTIGATING TAILORED TREATMENT WITH INFLIXIMAB FOR ACTIVE LUMINAL CROHN'S DISEASE

Een gerandomiseerd, gecontroleerd onderzoek naar een passende behandeling met Infliximab bij patiënten met actieve luminale ziekte van Crohn

Essai contrôlé randomisé evaluant le benefice d’un traitement par infliximab « a la carte » dans la maladie de Crohn luminale active

A.3.1

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

A RANDOMIZED CONTROLLED TRIAL INVESTIGATING TAILORED TREATMENT WITH INFLIXIMAB FOR ACTIVE LUMINAL CROHN'S DISEASE

A.3.2

Name or abbreviated title of the trial where available

TAILORIX

A.4.1

Sponsor's protocol code number

2010-2

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01442025

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	GETAID
B.1.3.4	Country	France
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	JANSEN Biologics
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	MSD
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	BVBA JCP
B.5.2	Functional name of contact point	Joos Evelyne
B.5.3	Address:
B.5.3.1	Street Address	Broekstraat 16
B.5.3.2	Town/ city	Heusden
B.5.3.3	Post code	9070
B.5.3.4	Country	Belgium
B.5.4	Telephone number	32477780202
B.5.5	Fax number	3292703317
B.5.6	E-mail	joos.evelyne@gmail.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	INFLIXIMAB
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN BIOLOGICAL BV
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	INFLIXIMAB
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	INFLIXIMAB
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Luminal active Crohn's Disease

E.1.1.1

Medical condition in easily understood language

Active Crohn's Disease

E.1.1.2

Therapeutic area

Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate whether sustained steroid-free remission between W22 and W54 and mucosal healing at 1 year can be achieved using IFX trough level measurements and adjustment of dosing based upon these levels by means of two different standardized algorithms in comparison with ‘standard of care’ IFX treatment and its effects on clinical and endoscopic outcomes.

E.2.2

Secondary objectives of the trial

- proportion of patients with sustained remission from week 14 onwards
- proportion of patients with sustained steroid free remission from week 14 onwards
- Proportion of patients with sustained IFX levels > 3 µg/ml
- clinical (CDAI) laboratory (hsCRP, Fecal calprotectin) and endoscopic status at all visits beyond week 14

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

MRI healing at week 52 scored with the Rimola (Barcelona) scoring system

E.3

Principal inclusion criteria

 Age > 18 years
Active CD (CDAI>220) and signs of active inflammation as evidenced by elevated serum hsCRP levels (>5 mg/L) and/or elevated fecal calprotectin levels (>250 µg/g) and endoscopically visible ulcers.
Patients must be naïve to biologics with indication for starting anti-TNF therapy in accordance with national reimbursement criteria.
Patients must be naïve to thiopurines or have failed therapy with 1 thiopurine; in which case AZA or 6MP will be continued: Patients previously intolerant to Azathioprine or 6-MP can start with the other thiopurine or with Methotrexate (MTX) per investigators discretion. Patient intolerant to standard doses of AZA or 6-MP can start at a lower dose per investigators discretion. However, the dose should remain stable for the duration of the trial, except if intolerance leading to discontinuation. 
Patients failing MTX can continue on MTX with infliximab 
Ongoing steroids are allowed if dose remains stable for at least 2 weeks, prior to screening until inclusion then tapered as per protocol and at a maximum of prednisone 40 mg/d or budesonide 9 mg/day
Patients who consent to receiving Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with their current Azathioprine, 6-MP or MTX.
Adequate contraception for women of childbearing potential or their partner who must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last IFX treatment.

E.4

Principal exclusion criteria

Absence of endoscopically visible ulcers
Ongoing steroid therapy at doses > 40 mg/d prednisolone equivalent
Previous intolerance to Azathioprine and /or 6-MP or intolerance to one or both with impossibility to use the other drug or MTX (e.g. pancreatitis, severe leucopenia, hypersensitivity).
Ongoing infections
Prior use of biologic therapies
Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer
Indication for immediate surgery
Critical gastrointestinal stricture with obstructive symptoms and/or presence of abscess.
Pregnant or breast-feeding woman.
Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools
Active tuberculosis. Positive tuberculosis screen per local guidelines
Untreated latent tuberculosis (see national recommendations. Appendix 2), latent TB is allowed if treated for at least 6 months
Patients with moderate or severe heart failure
Patients with a history of hypersensitivity to infliximab, other murine proteins, or to any of the excipients.
HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months.
Azathioprine or 6-MP in combination with allopurinol or with other myelotoxic therapy (a washout period of 7 days is required for allopurinol or other myelotoxic therapy)
Non-compliant subjects.
Participation in another therapeutic study

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with steroid-free remission between w22 and w54 (CDAI < 150) and endoscopic healing at W54 in CD patients treated with infliximab and azathioprine, 6MP or MTX using standard therapy or tailored treatment based on infliximab trough levels in addition to the usual clinical parameters.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 54 after inclusion

E.5.2

Secondary end point(s)

• Clinical remission (CDAI <150) at each visit and the whole study period
• Endoscopic evaluation at W12 and W54
o percentage of patients in each group with absence of ulcers;
o percentage of patients in each group with >50% improvement in CDEIS/SES-CD relatively to baseline (W0)
o percentage of patients in each group with CDEIS <3
• MR Enterography at week 0 and 54 at the centres where this procedure is standard of care with assessment of the Barcelona index.
• IFX Trough levels at each visit and every 4 weeks through the whole study period
• Fecal calprotectin and hsCRP levels at all visits
• Frequency of Adverse reactions (in specific infusion reaction and infections)
• Frequency of loss of response, defined as an increase of CDAI by 70 points compared to the previous measurement and elevated hsCRP or fecal calprotectin > 250. Frequency of flares hospitalizations and CD related surgeries
• Number and dose of co-medication
• Pharmaco-economic evaluation: disease and treatment related costs
• Correlations:
o mucosal healing vs. IFX levels
o mucosal healing vs. CRP
o mucosal healing vs. faecal calprotectin

E.5.2.1

Timepoint(s) of evaluation of this end point

Each visit
Week 0, week 12 and week 54 for endoscopic evaluation

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

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Same medical product at different dosage

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Last visit of last subject in the trial

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception