Clinical Trials Register

Summary
EudraCT Number:	2015-004618-10
Sponsor's Protocol Code Number:	PACIFIC
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:	2015-11-20
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

2015-004618-10

A.3

Full title of the trial

Study of the inter-individual variation of PhArmaCo-kinetics of InFliximab during treatment Induction in patients with Crohn’s disease and Ulcerative Colitis

A.3.1

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

PhArmaCo-kinetics of InFliximab during treatment Induction

A.4.1

Sponsor's protocol code number

PACIFIC

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	CUB- Hopital Erasme
B.1.3.4	Country	Belgium
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	BIRD Group
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CUB- Hopital Erasme
B.5.2	Functional name of contact point	Liefferinckx
B.5.3	Address:
B.5.3.1	Street Address	808 route de Lennik
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1070
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003225556196
B.5.5	Fax number	003225556197
B.5.6	E-mail	claire.liefferinckx@ulb.ac.be

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	Remsima
D.2.1.1.2	Name of the Marketing Authorisation holder	Celltrion Healthcare Hungary Kft
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Powder for concentrate 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.3.9.3	Other descriptive name	Remsima
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 10
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)	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	Yes
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.IMP: 2
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	Remicade
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Biologics B.V
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Powder for concentrate 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.3.9.3	Other descriptive name	Remicade
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 10
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)	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	Yes
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.IMP: 3
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	Inflectra
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Powder for concentrate 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.3.9.3	Other descriptive name	Inflectra
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 10
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)	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	Yes
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

Patients with Crohn disease or Ulcerative Colitis which need biotherapy (antibody against TNF-a)

E.1.1.1

Medical condition in easily understood language

Patients with Crohn disease or ulcerative colitis which need biotherapy (antibody against TNF-a)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of the inter-individual variability of the pharmacokinetics of infliximab level and antibodies to infliximab during induction treatment and correlation with clinical response at W14 and W30

E.2.2

Secondary objectives of the trial

Proportion of patients in steroid-free remission at W10-14 w/o normal CRP and/or fecal calprotectin levels

Sustained steroid-free clinical response at W30 w/o normal CRP and/or fecal calprotectin levels and mucosal healing

Sustained steroid-free clinical remission at W30 w/o normal CRP and/or fecal calprotectin levels

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with clinical response or remission, and/or normal CRP and/or normal fecal calprotectin levels at W14 and 30

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels > 3 μg/ml at W14 and W30 without need for optimization

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels in third and fourth quartile at W14 and W30

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age > 18 years

Moderate-to-severe CD (HBI≥8) with endoscopically visible ulcers or moderate-to-severe and severe UC (Mayo Score ≥6) and Mayo endoscopic subscore >1 (APPENDIX 1-2-3) (a patient with active disease without CRP can be included)

Patients must be starting on infliximab (Remicade (MSD) or CT-P13: Remsima (Mundipharma) or Inflectra (Hospira)) in accordance with national reimbursement criteria or a washout period of 8 weeks will be observed before starting any new anti-TNF therapy after vedolizumab and 4 weeks after adalimumab before starting infliximab

Patients may be naïve to thiopurines or have failed therapy with 1 thiopurine; in which case AZA or 6MP will be either continued or stopped: The dose must remain stable 4 weeks before beginning the study. 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 or AZA or 6MP can be stopped per investigators discretion. However, if the immunomodulator is continued or introduced during screening period, 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 was stable 2 weeks before beginning the study with a maximum of prednisone 16 mg/d or budesonide 9 mg/day and should be tapered in 2 weeks.

Patients who consent to receive 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

Women must have a contraceptive method

E.4

Principal exclusion criteria

Absence of endoscopically visible ulcers
Ongoing steroid therapy at doses > 16 mg/d prednisolone or equivalent
Ongoing infections
Previous use of IFX
Prior use of biologic therapies excepted if a washout period of 8 weeks is respected
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, latent TB is allowed if treated for at least 6 months
Patients with moderate or severe heart failure
Patients with multiple sclerosis or lupus disease
Patients with a history of hypersensitivity to infliximab, or to any of the excipients
HIV, HBV, HCV 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)

E.5.1.1

Timepoint(s) of evaluation of this end point

The timepoints of evaluation for the primary endpoint will be done at the end of induction treatment (at 6 weeks)

The correlation between induction treatment and clinical response will be done at W14 and W30

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

The timepoints of evaluation for the secondary endpoints will be done at:
- W10-14 for the first
- W14 and W30 for the other secondary endpoints

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

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

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:

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

F.3.3.2

Women of child-bearing potential using contraception

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

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)

This trial is an observational study where the treatment is applied according the standards of practice. So, at the end of the study, the treatment remains identical with a classic follow-up.

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

2015-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-19

P. End of Trial
P.	End of Trial Status	Ongoing

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