Efficacy of OM-85 in Preventing Recurrent Respiratory Tract Infections with Wheezing in Children Aged 6 Months to 5 Years: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of short- and long-term treatment with OM 85 compared to placebo in reducing the number of **Respiratory Tract Infections** (RTIs) in children aged between 6 months and 5 years who experience recurrent RTIs associated with **Wheezing Lower Respiratory Illness** (wLRI) over a 12-month treatment period. This is clinically relevant as it aims to address the burden of recurrent respiratory infections in a vulnerable pediatric population, potentially reducing morbidity and healthcare utilization.

Secondary objectives include assessing the efficacy of OM 85 versus placebo in reducing the number of wLRIs during the same 12-month treatment period. This further evaluation is crucial for understanding the broader impact of OM 85 on respiratory health in children, beyond the primary endpoint of RTI reduction.

The clinical trial involves a total of **28 participants** who are children aged between 6 months and 5 years, with a specific focus on those experiencing recurrent **Respiratory Tract Infections** (RTIs) associated with Wheezing Lower Respiratory Illness (wLRI). The study population includes both male and female subjects, and it is noted that the trial involves a vulnerable population due to the young age of the participants. Selection criteria required that children have a history of multiple RTIs, with specific thresholds for episodes depending on age, as reported by parents or legal authorized representatives. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Participants were selected based on their medical history and the provision of informed consent by their guardians. The study aims to evaluate the efficacy of OM 85 compared to a placebo in reducing the number of RTIs over a 12-month treatment period.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, multicenter, Phase 4 study. It aims to evaluate the efficacy of OM-85 (Broncho Vaxom) in both short- and long-term treatment compared to a placebo in preventing **respiratory tract infections** (RTIs) in children aged between 6 months and 5 years who have wheezing lower respiratory illness. The trial is expected to last for a total duration of 12 months, with the estimated recruitment start date being December 12, 2022, and the estimated end date being November 30, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age and history of RTIs. The baseline/randomization visit (Visit 2) will follow, where eligible participants will be randomly assigned to receive either the active treatment or placebo. Subsequent follow-up visits will be scheduled throughout the 12-month treatment period to monitor the rate of RTIs and wheezing lower respiratory illnesses (wLRIs), which are the primary and secondary endpoints, respectively. The end-of-study visit will conclude the trial, assessing the overall efficacy and safety of the treatment.

Participant involvement is expected to last for the entire 12-month treatment period unless conditions arise that necessitate early termination. Such conditions may include adverse reactions, withdrawal of consent, or any other medical reasons deemed significant by the study investigators. The trial will adhere to strict ethical guidelines, ensuring that informed consent is obtained from the parents or legal authorized representatives (LAR) of the subjects before any study-specific procedures are performed.

The clinical trial involves the administration of **BRONCHO-VAXOM® Kinder**, which is a hard capsule formulation containing **lyophilized bacterial lysates** of various bacterial species, including **Haemophilus influenzae**, **Streptococcus (Diplococcus) pneumoniae**, **Klebsiella pneumoniae and ozaenae**, **Staphylococcus aureus**, **Streptococcus pyogenes and viridans**, and **Moraxella (Branhamella/Neisseria) catarrhalis**. The active substance is standardized as OM-85 lyophilisate. The dosage for this medication is 3.5 mg per capsule, with a maximum daily dose of 3.5 mg and a total maximum dose of 420 mg over the treatment period. The route of administration is oral, and the treatment is designed to be administered over a 12-month period. The pharmaceutical form is a hard capsule, and the product is authorized in Germany under the marketing authorization number 34A/83.

The study also includes a **placebo** comparator, which is designed to match the BRONCHO-VAXOM® Kinder in appearance but does not contain the active bacterial lysates. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the active treatment, with the same frequency and duration, to provide a valid comparison of efficacy and safety outcomes.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary efficacy endpoint is the rate of **Respiratory Tract Infections (RTIs)** during the 12-month treatment period. This is defined as the number of RTIs experienced by a subject during the treatment period. The secondary endpoint focuses on the rate of wheezing Lower Respiratory Illnesses (wLRIs) during the same period, defined as the number of wLRIs experienced by a subject.

The trial is designed as a randomized, placebo-controlled, 3-arm, double-blind, multicenter, Phase 4 study. It aims to assess the efficacy of short- and long-term treatment with OM-85 (Broncho Vaxom) compared to placebo in preventing RTIs in children aged between 6 months and 5 years who have recurrent RTIs associated with wLRI. The treatment period spans 12 months, during which the efficacy parameters will be measured and collected. The analysis will focus on the reduction in the number of RTIs and wLRIs experienced by the subjects.