Clinical Trial Results:
Randomized, Placebo-controlled, Clinical Trial to Evaluate the Efficacy of Probiotic Bacillus Clausii in the Treatment of Pediatric Patients With Irritable Bowel Syndrome
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Summary
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EudraCT number |
2018-004519-31 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
25 Nov 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Jun 2021
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First version publication date |
10 Jun 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ENTERL08784
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Study name: BaclauSII | ||
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Sponsors
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Sponsor organisation name |
Sanofi Aventis de México SA de CV
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Sponsor organisation address |
Av. Universidad 1738 Coyoacán Centro CDMX, Z.P., Mexico, 04000
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Public contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Feb 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Nov 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the proportion of subjects with clinical improvement of symptoms (assessed with Global Assessment Questions) between Bacillus clausii versus placebo groups, both added to conventional treatment, at Week 8, in 6 to less than (<) 18-year-old subjects with irritable bowel syndrome (IBS).
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
11 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Mexico: 259
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Worldwide total number of subjects |
259
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
154
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Adolescents (12-17 years) |
105
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at multiple sites in Mexico. A total of 311 subjects were screened from 11-Mar-2019 to 10-Jul-2020, of which 52 subjects were non-randomised. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 259 subjects were randomised and treated in this study. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Bacillus clausii | |||||||||||||||||||||
Arm description |
Subjects received Bacillus clausii spores once daily (QD) for 8 weeks. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Enterogermina®
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Investigational medicinal product code |
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Other name |
Bacillus clausii spores
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Oral suspension of Bacillus clausii at total daily dose of 4 billion colony forming units (CFU) per day, divided in 5 millilitres (mL) per vial of 2 billion CFU, QD every morning prior to meal.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Subjects received placebo matched to Bacillus clausii QD for 8 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Oral suspension of match placebo to Bacillus clausii vials QD every morning prior to meal.
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Baseline characteristics reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Subjects received Bacillus clausii spores once daily (QD) for 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to Bacillus clausii QD for 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Subjects received Bacillus clausii spores once daily (QD) for 8 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to Bacillus clausii QD for 8 weeks. | ||
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End point title |
Percentage of Subjects With Clinical Improvement of Symptoms at Week 8 (Global Assessment): Intention-to-treat (ITT) Population | ||||||||||||
End point description |
Response rates was defined as subjects with clinical improvement of symptoms in the global assessment questions: a) ‘How well did the medication relieve your symptoms?’, where satisfaction with treatment was rated as ‘Excellent’ or ‘Good’; and b) ‘Overall how do you feel your problem is?', where symptom relief was rated as ‘Better’. Treatment responders was defined as subjects having satisfaction with treatment and symptoms relief at Week 8. Analysis was performed on ITT population that included all randomised subjects, analyzed according to the treatment group allocated by randomization.
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End point type |
Primary
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End point timeframe |
Week 8
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Statistical analysis title |
Bacillus clausii versus Placebo | ||||||||||||
Comparison groups |
Bacillus clausii v Placebo
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Number of subjects included in analysis |
259
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.8182 | ||||||||||||
Method |
Chi-square test | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
-4.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-13.5 | ||||||||||||
upper limit |
3.9 | ||||||||||||
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End point title |
Percentage of Subjects With Clinical Improvement of Symptoms at Week 8 (Global Assessment): Per-protocol (PP) Population | ||||||||||||
End point description |
Response rates was defined as subjects with clinical improvement of symptoms in the global assessment questions: a) ‘How well did the medication relieve your symptoms?’, where satisfaction with treatment was rated as ‘Excellent’ or ‘Good’ ; and b) ‘Overall how do you feel your problem is?', where symptom relief was rated as ‘Better’. Treatment responders was defined as subjects having satisfaction with treatment and symptoms relief at Week 8. Analysis was performed on PP population that included all subjects who completed the study without major protocol deviations (may include errors in the allocation of the Investigational Medicinal Product (IMP), the use of treatments not allowed by protocol, poor adherence to treatment (compliance <20%), or lost to follow-up).
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End point type |
Primary
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End point timeframe |
Week 8
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Statistical analysis title |
Bacillus clausii versus Placebo | ||||||||||||
Comparison groups |
Bacillus clausii v Placebo
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Number of subjects included in analysis |
146
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.4332 | ||||||||||||
Method |
Chi-square test | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
1.1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-9.9 | ||||||||||||
upper limit |
12.1 | ||||||||||||
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End point title |
Percentage of Subjects With Clinical Improvement of Symptoms at Week 4 (Global Assessment) | ||||||||||||
End point description |
Subjects with clinical improvement of symptoms was assessed using global assessment questions: a) ‘How well did the medication relieve your symptoms?’, where satisfaction with treatment was rated as ‘Excellent’ or ‘Good’ ; and b) ‘Overall how do you feel your problem is?', where symptom relief was rated as ‘Better’. Treatment responders was defined as subjects having satisfaction with treatment and symptoms relief at Week 4. Analysis was performed on ITT population.
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End point type |
Secondary
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End point timeframe |
Week 4
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With Clinical Improvement of Symptoms at Week 4 and Week 8: Assessed by Subject’s Global Assessment of Relief in Children (SGARC) | ||||||||||||||||||
End point description |
Clinical Improvement of symptoms by SGARC was assessed by asking a question from subject/caregiver: “Consider how your child felt this past week in regard to his or her IBS; especially the overall well-being, symptoms of stomach discomfort, pain, and altered bowel habits. Compared with the way he or she usually felt before entering the study, how do you rate the relief of symptoms during the last week?” Subject/Caregiver responded on a scale ranging from 0-4, where: 0=Complete relief; 1=Considerable relief; 2=Somewhat relieved; 3=Unchanged and 4=Worse, where higher scores indicated worse outcomes. Responders to the treatment were defined as subjects with a complete relief or a considerable relief. Analysis was performed on ITT population. Here, "number of subjects analysed" signifies number of subjects evaluable for this endpoint and "n" signifies number of subjects with available data for specified category for each arm, respectively.
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End point type |
Secondary
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End point timeframe |
Weeks 4 and 8
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Days With Bloating Episodes | |||||||||||||||||||||
End point description |
Abdominal distention/bloating was assessed by 3-point likert scale that consisted of single question, i.e., “Compared to the way you felt before entering the study, have your abdominal distention/bloating symptoms over past 4 weeks been”. Subject/Caregiver responded on scale that ranged from 1 to 3, where 1=Better; 2=Same; and 3=Worse, where higher scores indicated worst outcomes. Percentage of days with bloating episodes was calculated as: percentage of days with bloating at Visit i = total number of days with bloating episodes (between Visit i and Visit i-1)/total number of days between Visit i and Visit i-1 *100; where number of visit: i = 2 (Week 4), 3 (Week 8), 4 (Week 16); expressed in terms of mean and standard deviation in this endpoint. Analysis was performed on ITT population. Here, "number of subjects analysed" signifies number of subjects evaluable for this endpoint and "n" signifies number of subjects with available data for specified category for each arm, respectively.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 16
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Mean Number of Abdominal Pain Episodes Per Day | |||||||||||||||||||||
End point description |
Mean number of abdominal pain episodes (according to the subject diary information) by day was calculated using formula: mean number of abdominal pain per day at Visit i = sum of all number of abdominal pain episodes (between Visit i and Visit i-1)/total number of days (between Visit i and Visit i-1), where number of Visit i = 2 (Week 4), 3 (Week 8), 4 (Week 16). Analysis was performed on ITT population. Here, "number of subjects analysed" signifies number of subjects evaluable for this endpoint and "n" signifies number of subjects with available data for specified category for each arm, respectively.
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End point type |
Secondary
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End point timeframe |
Weeks 4, 8 and 16
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| No statistical analyses for this end point | ||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs were collected from the time from the IMP administration up to 1 day after last IMP administration regardless of seriousness or relationship to IMP.
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Adverse event reporting additional description |
Reported adverse events (AE) were treatment-emergent AE that developed or worsened during treatment-emergent period (time from the IMP administration up to 1 day after last IMP administration). Analysis was performed on safety population that included subjects who had actually received at least 1 dose or part of a dose of IMP.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Subjects received Bacillus clausii spores QD for 8 weeks. | |||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to Bacillus clausii QD for 8 weeks. | |||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
