Clinical Trials Register

Summary
EudraCT Number:	2011-003418-18
Sponsor's Protocol Code Number:	SMR2268/TheMIBSStudy
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-11-12
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

Norway - NOMA

A.2

EudraCT number

2011-003418-18

A.3

Full title of the trial

A Randomised, Double Blind, Placebo Controlled, Multi-centre, Parallel Group, Interventional Study of Mesalazine (Asacol®) Treatment in IBS and the Evaluation of Rectal Inflammatory Status using the Mucosal Patch Technique

A.3.1

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

A Randomised, Double Blind, Placebo Controlled, Multi-centre, Parallel Group, Interventional Study of Mesalazine (Asacol®) Treatment in Irritable Bowel Syndrome and the Evaluation of Rectal Inflammation using the Diagnostic Tool 'Mucosal Patch Technique'

A.3.2

Name or abbreviated title of the trial where available

The MIBS Study

A.4.1

Sponsor's protocol code number

SMR2268/TheMIBSStudy

A.5.4

Other Identifiers

Name:	MucoMPO	Number:	Mucosal Patch Technique
Name:	Mesalazine treatment in IBS	Number:	MIBS study

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	Sahlgrenska University Hospital
B.1.3.4	Country	Sweden
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	VINNOVA
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Tillotts Pharma AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Sahlgrenska University Hospital
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Diagnostics Development, P&M Venge AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sahlgrenska University Hospital
B.5.2	Functional name of contact point	Principal Investigator
B.5.3	Address:
B.5.3.1	Street Address	Medicinkliniken
B.5.3.2	Town/ city	Göteborg
B.5.3.3	Post code	413 45
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+4631342 81 07
B.5.5	Fax number	+4631741 29 17
B.5.6	E-mail	hans.tornblom@vgregion.se

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	Asacol
D.2.1.1.2	Name of the Marketing Authorisation holder	Tillotts Pharma AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MESALAZINE
D.3.9.1	CAS number	89-57-6
D.3.9.4	EV Substance Code	SUB08782MIG
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	800
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	No

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

Irritable Bowel Syndrome

E.1.1.1

Medical condition in easily understood language

Irritable Bowel Syndrome

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10023003
E.1.2	Term	Irritable bowel syndrome
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 assess the effect of mesalazine (Asacol®) treatment compared to placebo on IBS symptoms.

E.2.2

Secondary objectives of the trial

To assess mesalazine (Asacol®) treatment compared to placebo regarding:

1) Inflammatory mediators measured by the Mucosal Patch Technology
2) Effects on immune cells and cytokines in mucosal biopsies
3) Calprotectin levels in faeces
4) Individual IBS symptom parameters

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Males and females aged 18 to 70 years, both inclusive
2) Subject is diagnosed with irritable bowel syndrome (IBS) prior to Screening based on the Rome III diagnostic criteria.
3) Subject presents with IBS symptom intensity of at least moderate level; defined as an IBS Severity Scoring System (IBS
SSS) score of ≥175 at both Screening (Visit 1, Day -21±2) and Baseline (Visit 2, Day 0)
4) Provision of signed informed consent

E.4

Principal exclusion criteria

1) Subjects who are unable to understand the written and verbal instructions
2) Presence of a systemic inflammatory disease
3) Presence of other gastrointestinal diseases likely to explain the IBS symptoms
4) Presence of other severe somatic disease
5) Treatment with non-steroidal anti-inflammatory drugs (NSAID), opioid analgetics or acetylsalicylic acid (ASA) compounds within 7 days prior to screening (Visit 1, Day -21±2)
6) Treatment with systemic antibiotics within 28 days prior to Screening (Visit 1, Day -21±2)
7) Treatment with immunosuppressant drugs within 28 days prior to Screening (Visit 1, Day -21±2)
8) Other significant medical treatment, which, in the opinion of the investigator, may compromise the safety and efficacy objectives of the study, within 28 days prior to Screening (Visit 1, Day -21±2)
9) Previously confirmed allergy towards ASA or mesalazine
10) Presence of renal disease and/or concomitant treatment with medications with potential renal side effects
11) Current ongoing infection
12) History of, or current, drug or alcohol dependence
13) Pregnant or lactating women
14) Subjects suspected not to follow instructions based on the discretion of the Investigator
15) Current participation in other intervention studies
16) Female subjects of childbearing potential unwilling to use adequate contraceptive measures throughout the duration of the study. For the purpose of this study, adequate contraception is defined as:
- oral, injected or implanted hormonal methods of contraception; OR
- placement of an intrauterine device (IUD) or intrauterine system (IUS); OR
- barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

Note: Male sterilisation or abstinence are not acceptable methods of birth control and would preclude enrolment in the study.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable will be an assessment of mesalazine (Asacol®) treatment compared with placebo on IBS symptoms. The main measurement parameters of symptom alleviation will be a global symptom score showing satisfactory symptom relief ≥50% of the time as recorded on a weekly basis in a separate questionnaire for the duration of the treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary efficacy variable will be measured through weekly assessments of satisfactory symptom relief as evaluated by the patient from the start of treatment (week 0) up until the end of treatment (week 8)

E.5.2

Secondary end point(s)

Secondary efficacy variables will be assessments of mesalazine (Asacol®) treatment compared to placebo regarding:

1. Inflammatory mediators measured by the Mucosal Patch Technology (MPT), e.g. neutrophil mediators, eosinophilic mediators, mast cell activity mediators and cytokines
2. Effect on immune cells and cytokines in mucosal biopsies
3. Levels of calprotectin in faeces
4. Total IBS-SSS score
5. Individual symptom parameters in IBS-SSS and the IBS diary
6. Exploratory responder variables:
a. satisfactory symptom relief ≥75% of the time
b. reduction in IBS-SSS ≥50 at end of treatment compared to randomization

E.5.2.1

Timepoint(s) of evaluation of this end point

IBS-SSS will be evaluated on a biweekly basis for the entire duration of the treatment period (Week 0 to Week 8) with one final evaluation performed during the follow-up phase (Week 10). At each timepoint, the IBS-SSS as a whole and individual parametres will be compared against baseline.

The patient will be asked to complete the diary during the run-in period of the study (Day -14±2 to Day 0, inclusive), during the last two weeks of treatment (Day 42±2 to Day 56±2) and during follow-up (Day 56±2 to Day 70±2).

Inflammatory mediators, levels of calprotectin in faeces, effect on immune cells and cytokines in mucosal biopsies will be measured as change from baseline (Week 0) at the end of the treatment period (Week 8).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

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

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

The end of the trial will be defined as the timepoint when the last patient in the study completes the final follow-up visit at Week 10 in the study. This is given that no reasons for unscheduled visits going beyond this timepoint will exist for any patients.

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:

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