E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
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 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the proportion of patients with clinical improvement of symptoms (assessed with Global Assessment Questions) between B. clausii versus placebo groups, both added to conventional treatment, at week 8, in 6 to <18-year-old patients with IBS. |
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E.2.2 | Secondary objectives of the trial |
To compare the proportion of patients with clinical improvement of symptoms (assessed with Global Assessment Questions) between B. clausii versus placebo groups, both added to conventional treatment, at week 4.
To compare clinical improvement of symptoms (assessed with SGARC) between B. clausii versus placebo, at weeks 4 and 8.
To compare mean number of stools, consistency of stools with Bristol Stool Form Scale, distention/bloating(assessed with 3-point likert scale),abdominal pain, abdominal pain intensity with Face Pain Scale-Revised (FPS-R), global improvement of symptoms with 7-point likert scale) between B. clausii versus placebo, at weeks 4, 8 and 16.
To compare IBS behavior and quality of life between B. clausii versus placebo, at weeks 4, 8 and 16.
To compare serum cytokine levels of B. clausii versus placebo, at weeks 0, 8 and 16 and change from week 0 to weeks 8 and 16.
To compare the incidence of adverse events between B. clausii and placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients aged between 6 and <18 years old with a diagnosis of IBS, based on the Rome IV criteria.(1) Accordingly, the diagnostic criteria for IBS must be fulfilled for at least 2 months before diagnosis, and must include all of the following:
Abdominal pain at least 4 days per month associated with one or more of the following:
Related to defecation
A change in frequency of stool
A change in form (appearance) of stool
In children with constipation, the pain does not resolve with resolution of the constipation (children in whom the pain resolves have functional constipation, not IBS)
After appropriate evaluation, the symptoms cannot be fully explained by another medical condition
The informed consent form should be provided by the patient and by a parent or legal guardian (and informed assent form should be provided by the patient if applicable) and witnesses |
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E.4 | Principal exclusion criteria |
Patients who have received treatment with antibiotics or probiotics in the 2 months prior to the study screening (Visit 0)
Growth failure or malnutrition
Previous history of abdominal surgery
Known gastrointestinal co-morbidity, such as: inflammatory bowel disease, celiac disease, H. Pylori infection
Lactose intolerance, which have not yet received elimination diet of lactose
Exocrine pancreatic failure
History of bleeding from digestive tract low in the last 2 years prior, or who have abnormal endoscopic or histological studies
Endometriosis diagnosis
History of abuse in the consumption of alcohol or drugs
Stool ova and parasite positive to pathogens parasite
History of significant infections or inflammatory processes during pre-enrollment.
Patient who has participated or is participating in another clinical-pharmacological study in the three months prior to enrollment
Patient not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures Patients that fulfill any contraindications for the Sanofi compound according to the current level of knowledge of Enterogermina®.
Serious adverse reactions or hypersensitivity to any drug product.
Pregnant or breastfeeding adolescent woman
Adolescent woman of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy (see contraceptive guidance in Appendix A). Adolescent woman who are not sexually active, abstinence from sexual intercourse is an acceptable form of birth control, within those who are willing or able to be tested for pregnancy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in the proportion of treatment responders : Response rate defined with the Global Assessment Questions:
a) ‘‘How well did the medication relieve your symptoms? (satisfaction with treatment) (excellent, good, fair, poor, failed)” rated as excellent or good
and
b) ‘‘Overall how do you feel your problem is? (symptom relief) (worse, same, better)’’rated as better,
at week 8. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1 - Difference in the proportion of treatment responders : Response rate defined as ‘‘How well did the medication relieve your symptoms? (satisfaction with treatment) rated as excellent or good and ‘‘Overall how do you feel your problem is? (symptom relief) rated as better, at week 4.
2 - Response to treatment in SGARC (Subject’s Global Assessment of Relief for Children with IBS ) : Response to treatment (0=complete relief or 1=considerable relief in SGARC)
3 - consistency of stools assessed by BSFS (Bristol Stool Form Scale ) : Percentage of consistency of stools for each type
4 - Number of stools assessed by BSFS (Bristol Stool Form Scale ) : Mean Number of stools by day
5 - Bloating : Percentage of bloating
6 - Number of abdominal pain assessed by FPS-R ( Face Pain Scale-Revised ) : Mean number of abdominal pain
7 - IBS Behavior assessed with Behavior scale : Mean IBS Behavior
8 - incidence of Adverse event (AE) : Number of patient witn AE
9 - Quality of Life assessed with FDI ( Functional Disability Inventory ) : Change from week0 to weeks 4, 8 and 16 in Score of quality of life
10 - Serum cytokine levels : Change Serum cytokine levels (IL-12, TNF-α, IL-10 and TGF-β) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 : week 4
2 : week 4 and week 8
3, 4, 5, 6, 7 : week4 ; week 8 and week 16
8 : from Day 0 to week 16
9 : Week 0 ; week4 ; week8 and week 16
10 : weeks 0, 8 and 16 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |