EBV09/01

OM Pharma SA

22 rue du Bois-du-Lan, Geneva, Switzerland, CH-1217 Meyrin 2

Alexia Dolliner-Paire, ICTA PM, +33 380534000, bvdrops@icta.fr

Alexia Dolliner-Paire, ICTA PM, +33 380534000, bvdrops@icta.fr

No

No

Yes

Final

23 Oct 2012

Yes

17 Oct 2011

Yes

17 Oct 2011

No

To show that Broncho-Vaxom® drops decrease significantly the rate of Respiratory Tract Infections (RTIs) when compared to placebo.

The study was conducted in accordance with the principles of the Declaration of Helsinki (Seoul, October 2008) including amendments in force up to and including the time the study was conducted, the International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP), Committee for Proprietary Medicinal Products Guideline (CPMP/ICH/135/95), European Union Clinical Trial Directive (Directive 2001/20/EC) and applicable regulatory requirements. A subject could be included into the present study only after his/her parent(s) or legal representative declared in a written form their willingness to take part in the study. In order to be able to take this decision, they were previously informed by the investigator about the content and among others aims and methods of the planned study, as well as on the benefit/risk ratio. The information had to be given both orally and in a written form. For this statement, a Patient Information Sheet (PIS) was available, which was in agreement in its text structure with each reference IEC guidelines, the Declaration of Helsinki, current ICH and GCP guidelines, and the Sponsor policy. The statement gave also indications to the parent(s) or legal representative about the insurance coverage and the resulting regulations for the delimitation of damages, about the fact that the participation in the study was entirely voluntary and would have no effect on clinical care otherwise available, and about the possibility to withdraw the consent to participate at any time without penalty or loss of further medical treatment. The parent(s) or legal representative had to be informed that they had to notify the investigator of any other medical measures during the study period and that their child could not take part simultaneously in another trial.

13 Sep 2010

Yes

No

Czech Republic: 41

Hungary: 150

Italy: 45

Portugal: 2

Romania: 39

Belgium: 6

283

283

0

0

0

13

270

0

0

0

0

Period 1 (overall period)

Randomised - controlled

The boxes for the treatment had a randomisation number and the investigator was provided with sealed envelopes containing the code for each patient's randomisation number. The envelopes were checked at the end of study to ensure that the seals had not been broken. The code could only be broken under serious adverse events (SAEs) circumstances. The randomisation schedule was not available at the study centre, to the study monitors, project statisticians or the project teams of the Sponsor and CRO

Yes

Broncho-Vaxom®

Oral drops, solution

Oral use

The drug had to be taken with a drink (fruit juice, milk, water…) or a yoghurt on an empty stomach, in the morning. The daily dose was 10 drops of solution (320 μL) containing 3.5 mg of bacterial extract, following this schedule during the study: - The first 1-month period, each morning, so during approximately 30 days. - The third 1-month period, each morning of the first 10 days, so during approximately 10 days. - The fourth 1-month period, each morning of the first 10 days, so during approximately 10 days. - The fifth and last 1-month period, each morning of the first 10 days, so during approximately 10 days.

Placebo

Oral drops, solution

Oral use

Same as experimental product.

Broncho-Vaxom®

Placebo

Broncho-Vaxom®

Placebo

The total number of RTIs per subject was identified using the RTI form and was medically reviewed before database freeze, to ensure completeness of the RTIs. Coding was performed using MedDRA version 15.0. Respiratory infections which were complication of an initial infection were not counted as “new infection”. In order to be counted as a “new infection”, a symptom-free interval of ≥7 days between two infectious episodes had to be present. The Full Analysis Set (FAS; N=278) population was considered for the endpoints, consisting of those subjects who were randomised to treatment, received at least one dose of randomised treatment, and attended at least one post-baseline visit. The FAS was created in accordance with the Intent-To-Treat principles.

Primary

From the randomisation visit (Month 0 - Visit 1) to the end of the treatment period (Month 5 - Visit 6).

Non-parametric analysis, using a negative binomial model (SAS® procedure: proc GENMOD, link function=LOG and dist=BIN). The response variable was RTI occurrence, treatment group and countries were included as main effects in the model, and the log of time the subject was followed was used as an offset variable to take into account early dropouts and to adjust the regression estimates. A univariate analysis did not show a trend in favour of Broncho-Vaxom®vs placebo.

Broncho-Vaxom® v Placebo

278

Pre-specified

1.0308

2-sided

Standard deviation

1.39

Non-parametric analysis, using a negative binomial model (SAS® procedure: proc GENMOD, link function=LOG and dist=BIN). The response variable was RTI occurrence, treatment group and countries were included as main effects in the model, and the log of time the subject was followed was used as an offset variable to take into account early dropouts and to adjust the regression estimates. A multivariate analysis did not show a trend in favour of Broncho-Vaxom®vs placebo.

Broncho-Vaxom® v Placebo

278

Pre-specified

1.039

2-sided

Standard deviation

1.39

Subjects with recurrent RTIs were defined as subjects presenting 3 or more RTIs up to the end of treatment period/premature withdrawal (Visit 6 ).

Secondary

From Visit 1 to the end of treatment period (Month 5 - Visit 6).

Cochran-Mantel-Haenszel test, stratified by centres.

Broncho-Vaxom® v Placebo

278

Pre-specified

All adverse events (AEs) were collected from the time of signature of informed consent until Visit 7, i.e. 60 days after the last dose of study medication, which was considered as the safety follow-up period, so included in the whole study duration.

Intermediary Phone Calls (IPCs) were performed between each visit in order to assess the possible occurrence of RTIs. Unscheduled visits could be performed, among others because of occurrence of RTIs detected during IPCs, any worsening condition or other medical event.

15.0

Broncho-Vaxom®

Placebo