A Study to Assess the Efficacy and Safety of Daily OM-85 in Young Children With Recurrent Wheezing

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of daily OM-85 treatment compared to placebo in children aged 6 months to 5 years with recurrent wheezing

Detailed Description
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This study is a 12-months phase 2, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of daily treatment with OM-85 compared to placebo, when given on top of standard of care treatment, in reducing wheezing/asthma like episodes (WEs) during the 6-month treatment period in children aged 6 months to 5 years with previous recurrent WEs. Patients will be randomized in a 1:1 ratio to OM-85 or placebo. The study consists of screening period (Day -20 to Day -1), a treatment period of 6 months, and an observational period of 6 months without treatment. Thus, the total duration of the study for each patient will be 12 months (±10 days) + up to 20 days for screening.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 2 Study to Assess the Efficacy and Safety of Daily OM-85 Treatment vs. Placebo Given in Children Aged 6 Months to 5 Years With Recurrent Wheezing

Conditions
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Recurrent Wheezing, 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: Subjects who meet all the following criteria will be included in the study: Children of either gender, aged between 6 and 72 months (5 years inclusive). Children with recurrent wheezing: For ICS/LTRA naïve patients or intermittent users (patients using ICS treatment only during an upper RTI to prevent WE): ≥2 WEs including at least 1 severe episode (i.e., treated with OCS OR having triggered an ED visit/hospitalization), OR ≥3 WEs including at least one that triggered an unscheduled physician visit, in the 12 months prior to enrollment. For ICS/LTRA daily users: ≥1 severe WE (i.e., treated with OCS OR having triggered an ED visit/hospitalization) OR ≥2 WEs including at least one that triggered an unscheduled physician visit, as reported by parents or LAR of subject (i.e., guardians), in the 12 months prior to enrollment, while being on their daily controller therapy. Up-to-date vaccination status as per applicable State Vaccination Requirements for school/day-care entry. Parents or LAR have provided the appropriate written informed consent. Written informed consent must be provided before any study-specific procedures are performed including screening procedures. Note: If a subject is experiencing respiratory symptoms at time of screening, he/she could only be randomized once symptoms have resolved for at least one week. Exclusion Criteria: Known anatomic alterations of the respiratory tract. Wheezing documented to be caused by gastroesophageal reflux. Other known chronic respiratory diseases (e.g., tuberculosis or cystic fibrosis). Any known autoimmune disease. Known human immunodeficiency virus (HIV) infection or any known type of congenital or iatrogenic immune deficiency (including immunoglobulin (Ig) A deficiency). Known acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal function abnormalities. Children born prematurely i.e., before 34 weeks of gestational age. Children with an abnormally low or high weight for their age and height, if this would not allow safe completion of the clinical study in the opinion of the investigator. Any known neoplasia or malignancy. Treatment with the following medications: Systemic (intravenous or intramuscular) or OCS (e.g., oral prednisolone) within 4 weeks before study enrollment. Previous and/or concomitant immunosuppressants, immunostimulants, or gamma globulins within 6 months before study enrollment. Any major surgery within the last 3 months prior to study enrollment. Known allergy or previous intolerance to investigational drug. Any other clinical conditions, which in the opinion of the Investigator, would not allow safe completion of the clinical study. Other household members have previously been randomized in this clinical study. Inability to comply with the study requested visit schedule (e.g., expected relocation within 12 months of the screening for the study). Currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening or receiving other investigational agent(s). Note: Subjects with past, present, or at risk of COVID-19 should not be excluded from the study.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 72 Months

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OM-85<br>Patients will receive OM-85 capsules as a treatment for 6 months and will be under observation for 6 months. | Drug: OM-85<br>* OM-85 capsule (3.5mg) contents will be mixed with adequate quantity of water, fruit juice or milk/formula and orally administered once a day for 6 consecutive months.<br>|
| Placebo Comparator: Placebo<br>Patients will receive placebo capsules as a treatment for 6 months and will be under observation for 6 months. | Drug: Placebo<br>* Placebo capsule contents will be mixed with adequate quantity of water, fruit juice or milk/formula and orally administered once a day for 6 consecutive months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Wheezing/Asthma like episodes (WEs) | To assess the efficacy of OM-85 in reducing the rate of WEs compared to placebo during the 6-month Treatment period in children aged 6 months to 5 years with previous recurrent WEs. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of severe WEs | To assess the efficacy of OM-85 in reducing the rate of severe WEs compared to placebo during the 6-month Treatment period. | 6 Months | 
| Number of oral corticosteroid (OCS) treatments during 6-month treatment period | To assess the efficacy of OM-85 in reducing the use of oral corticosteroids for WEs compared to placebo during the 6-month Treatment period. | 6 Months | 
| Number of days with WEs | To assess the efficacy of OM-85 to decrease the cumulative number of days with WEs compared to placebo during the 6-month Treatment period. | 6 Months | 
| Rate of WEs and severe WEs | To assess the efficacy of OM-85 compared to placebo in reducing the rate of WEs and severe WEs during the 6-month Observational period. | From Month 6 up to Month 12 | 
| Number of OCS treatments during 6-month observational period | To assess the efficacy of OM-85 in reducing the use of oral corticosteroids for WEs vs. placebo during the 6-month observational period. | From Month 6 up to Month 12 | 
| Duration in days of WEs and severe WEs | To assess the efficacy of OM-85 compared to placebo in reducing the duration of WEs and of severe WEs during the 6-month Treatment period and the 6-month Observational period. | 12 Months | 
| Time to treatment failure | To assess the efficacy of OM-85 compared to placebo to prolong time to treatment failure, during the whole study period. | 12 Months | 
| Time to first, second and third WE | To assess the efficacy of OM-85 compared to placebo to prolong the time to first, second, and third WE. | 12 Months | 
| Number of routine asthma treatment | To assess the efficacy of OM-85 compared to placebo to reduce the amount of routine asthma treatment required to control acute WEs during the 6-month treatment period and the 6-month observational period. The number of routine asthma treatment will be assessed. | 12 Months | 
| Duration of routine asthma treatment | To assess the efficacy of OM-85 compared to placebo to reduce the amount of routine asthma treatment required to control acute WEs during the 6-month treatment period and the 6-month observational period. The duration of routine asthma treatment will be assessed. | 12 Months | 
| Percentage of patients with recurrent wheezing | To assess the efficacy of OM-85 compared to placebo in reducing the percentage of patients with ≥1 WEs during the 6-month treatment period and the 6-month observational period. | 12 Months | 
| Number of days with respiratory tract infection (RTIs) symptoms | To assess the efficacy of OM-85 compared to placebo in reducing the number of days with RTI symptoms during the 6-month treatment period and the 6-month observational period. | 12 Months | 
| Level of severity of RTI symptoms (Absent/Mild/Moderate/Severe) | To assess the efficacy of OM-85 compared to placebo in reducing the severity of RTI symptoms during the 6-month treatment period and the 6-month observational period. RTI symptoms severity will be assessed based on the symptom evaluation in the adapted Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K), other relevant symptoms indicative of an RTI (e.g., headache, body aches), and tympanic temperature as recorded by patient's parents or legally authorized representative (LAR). Severity of symptoms will be determined by using the following definitions: child does not have this = absent (no sign/symptom evident); a little bad = mild (sign/symptom clearly present but easily tolerated); bad = moderate (definite awareness of sign/symptom that is bothersome but tolerable); and very bad = severe (sign/symptom that is hard to tolerate and causes interference with activities of daily life and/or sleeping). | 12 Months | 
| Number of antibiotic cycles | To assess the efficacy of OM-85 compared to placebo in reducing the antibiotics treatment for an RTI during the 6-month treatment period and the 6-month observational period. | 12 Months | 
| Number of medical visits | To assess the efficacy of OM-85 compared to placebo in reducing the number of medical visits (hospitalizations, visits to emergency rooms, or to a physician/health care provider) due to respiratory events during the 6-month treatment period and the 6-month observational period. | 12 Months | 
| Number of days absent from daycare/school | To assess the efficacy of OM-85 compared to placebo in reducing the number of days of absence from daycare/school due to respiratory events during the 6-month treatment period and the 6-month observational period. | 12 Months | 
| Number of patients with adverse events (AEs) | To assess the safety of daily OM-85 treatment compared to placebo in children aged 6 months to 5 years with recurrent WEs during the 6-month treatment period and the 6-month observational period. | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Innate immune response, Type 1 immune response, Type 2 immune response, Bacterial lysate, Immunomodulation, EAGLE