OM-85 in Paediatric Recurrent Respiratory Tract Infections With Wheezing Lower Respiratory Illness

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of OM-85 compared to placebo in reducing the number of respiratory tract infections (RTIs) in children aged between 6 months and 5 years.

Detailed Description
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This is a Phase 4, randomised, double-blind, placebo-controlled study to assess the efficacy and safety of short- and long-term treatment with OM-85. The study will consist of screening (up to 20 days before randomisation), Treatment period of 12 months, and an Observational period of 6 months. A total of 426 subjects will be randomised in the study. The subjects will be randomised in a ratio of 1:1:1 ratio to receive either OM-85 for 12 consecutive months (BV-12 arm), or OM-85 for 3 consecutive months followed by matching placebo for 9 consecutive months (BV-3 arm), or placebo for 12 consecutive months (Placebo arm). The expected duration of subject participation is 18 months (+20 days)

Official Title
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A Randomised, Placebo-Controlled, 3-Arm, Double-Blind, Multicentre, Phase 4 Study to Assess the Efficacy of OM-85 (Broncho-Vaxom) Short- and Long-Term Treatment vs. Placebo in the Prevention of Respiratory Tract Infections in Children Aged Between 6 Months and 5 Years With Wheezing Lower Respiratory Illness

Conditions
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Respiratory Tract Infections, Wheezing Lower Respiratory Illness

Intervention / Treatment
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* Drug: OM-85
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of either gender aged between 6 months and 5 years, at Baseline/Randomisation (Visit 2) inclusive. For children ≥1 year of age, ≥4 RTIs (as reported by parents or LAR of subject), including ≥2 episodes of wLRIs (including ≥1 triggering hospitalisation or medical visit) within 12 months prior to enrolment. OR For children <1 year of age, ≥2 RTIs (as reported by parents or LAR of subject), including ≥1 episode of wLRIs (including ≥1 triggering hospitalisation or medical visit) within 6 months prior to enrolment. Parents or LAR of subject have provided the appropriate written informed consent. Written informed consent must be provided before any study-specific procedures are performed including screening procedures. Exclusion Criteria: Anatomic alterations of the respiratory tract. Other chronic respiratory diseases (e.g., tuberculosis, cystic fibrosis). Any autoimmune disease. HIV infection or any type of congenital or iatrogenic immune deficiency (including IgA deficiency). Known severe congenital heart disease. Haematologic diseases. Liver or kidney failure. New-borns before 34 weeks of gestational age. Malnutrition as per World Health Organization (WHO) definition. Any known neoplasia or malignancy. Treatment with the following medications: Injection or oral administration of steroids within 4 weeks prior to study enrolment. Previous and/or concomitant immunosuppressants, immunostimulants, or gamma globulins within 6 months prior to study enrolment. Previous use within last 6 months of enrolment or ongoing use of bacterial lysates. Any major surgery within the last 3 months prior to study enrolment. Known allergy or previous intolerance to investigational medicinal products (IMP). Any other clinical conditions, that in the opinion of the Investigator, would not allow safe completion of the clinical study. Other household members have previously been randomised in this clinical study. Subjects' families expected to relocate out of study area within 24 months of the initiation of the study. Currently enrolled in or has completed any other investigational device or drug study or receiving other investigational agent(s) within <30 days prior to screening. Parents or legally acceptable representative (LAR) who do not have access to internet connection. Wheezing documented to be caused by gastroesophageal reflux.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BV-12<br>Subjects will receive OM-85 treatment for 12 consecutive months. (10 days per month) | Drug: OM-85<br>* Subjects will be administered OM-85 3.5 mg capsules by mouth once daily. (10 days per month)<br>|
| Experimental: BV-3<br>Subjects will receive OM-85 treatment for 3 consecutive months, followed by matching placebo for 9 consecutive months. (10 days per month) | Drug: OM-85<br>* Subjects will be administered OM-85 3.5 mg capsules by mouth once daily. (10 days per month)<br>|
| Placebo Comparator: Placebo<br>Subjects will receive matching placebo for 12 consecutive months. (10 days per month) | Drug: Placebo<br>* Subjects will be administered Placebo once daily. (10 days per month)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of respiratory tract infections (RTIs) | The number of RTIs experienced by a subject during the Treatment period will be assessed. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of wheezing lower respiratory infections (wLRIs) experienced by a subject | The number of wLRIs experienced by a subject during the Treatment period will be assessed. This is the key secondary endpoint | 12 Months | 
| Rate of wLRIs | The number of wLRIs experienced by a subject during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Rate of respiratory tract infections (RTIs) | The number of RTIs experienced by a subject during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Proportion of subjects with recurrent RTIs | The proportion of subjects experiencing ≥3 RTIs during the first 6 months of treatment, and the number of subjects experiencing ≥4 RTIs during the full 12-month Treatment period will be assessed. | 12 Months | 
| Proportion of subjects with wLRIs | The proportion of subjects with wLRIs during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Rate of severe wheezing lower respiratory illness (SwLRIs) | The number of SwLRIs experienced by a subject during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Proportion of subjects with SwLRIs | The proportion of subjects with SwLRIs during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Time to first, second and third RTI and wLRI | Time to first, second and third RTI and wLRI will be assessed. | 18 Months | 
| Mean duration in days per RTI | Mean duration in days per RTI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Mean duration in days per wLRI | Mean duration in days per wLRI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Number of outpatient medical visits | Number of outpatient medical visits (hospitalisations, visits to emergency rooms, or to a physician/health care provider) due to an RTI and/or a wLRI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Number of absent days from day-care | Number of absent days from day-care due to an RTI and/or a wLRI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Number of antibiotic treatments for a respiratory event | Number of antibiotic treatments for a respiratory event during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Duration of antibiotic treatments for a respiratory event | Duration of antibiotic treatments for a respiratory event during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Number of systemic corticosteroids, inhaled corticosteroids (ICS) and β2-agonist treatments for a wLRI | Number of systemic corticosteroids, ICS and β2-agonist treatments for a wLRI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Duration of systemic corticosteroids, ICS and β2-agonist treatments for a wLRI | Duration of systemic corticosteroids, ICS and β2-agonist treatments for a wLRI during the Treatment period and during the Observational period will be assessed. | 18 Months | 
| Symptom duration as per the adapted Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K) questionnaire | Symptom duration during the Treatment period and during the Observational period will be assessed using WURSS-K questionnaire. Adapted WURSS-K is a valid and reliable illness-specific quality of life instrument that evaluates the impacts of RTIs on children. | 18 Months | 
| Symptom types as per the adapted WURSS-K questionnaire | Symptom types during the Treatment period and during the Observational period will be assessed using WURSS-K questionnaire. Adapted WURSS is a valid and reliable illness-specific quality of life instrument that evaluates the impacts of RTIs on children. | 18 Months | 
| Symptom severity as per the adapted WURSS-K questionnaire | Symptom severity during the Treatment period and during the Observational period will be assessed using WURSS-K questionnaire. Adapted WURSS is a valid and reliable illness-specific quality of life instrument that evaluates the impacts of RTIs on children. | 18 Months |