Immunomodulation by OM-85 (Broncho-Vaxom) in Early AD

A Randomised, Double-Blind, Placebo-controlled, 32-week, Phase IIa Trial to Investigate the Efficacy of OM-85 Versus Matched Placebo in Reducing Disease Severity Children Aged 3 to 24 Months With Early Clinical Diagnosis of Moderate Atopic Dermatitis

Clinical data suggest that treatment with OM-85, by inducing an early contact with bacterial extracts, could modulate the immunity of children with Atopic Dermatitis, and thus play an active role in the treatment of Atopic Dermatitis. The present trial will investigate the influence of administration of OM-85 in the paediatric population younger than 24 months with moderate atopic dermatitis. The efficacy and safety of OM-85 will be evaluated in children aged 3 to 24 months old with moderate Atopic Dermatitis who may benefit from treatment with OM-85. The placebo treatment period will serve as a reference and has been added to establish efficacy and safety.

In this study, the efficacy of OM-85 versus matched placebo in children with moderate AD (Atopic Dermatitis) in reducing disease severity shall be evaluated. Clinical data suggest that treatment with OM-85, by inducing an early contact with bacterial extracts, could modulate the immunity of children with AD, and thus play an active role in the treatment of AD. This will be a multicenter, randomised, double-blind, placebo-controlled exploratory phase IIa trial to assess the efficacy and safety of daily oral administration of OM-85 or matched placebo in children aged 3 to 24 months for 24 weeks. A total of 142 children with AD as defined by Hanifin and Rajka criteria and with moderate disease severity (EASI 7.1 - 21.0) at Screening will be enrolled into this trial in approximately 15 sites in Germany and potentially one additional European country. All screened subjects will receive a unique subject ID (Identification) number. Eligible subjects will be randomized at 1:1 ratio, stratified by age (≤12 months vs. >12 months) and disease severity (EASI <16 vs. ≥16) to one of the two treatments. They will receive either OM-85 or placebo for a 24-week treatment period followed by an observational period of 8 weeks without investigational medicinal products (IMP). The placebo will serve as reference in evaluating efficacy and safety of OM-85. The double blind, randomized trial design is selected to avoid bias concerning evaluation of the drug effects, including safety and efficacy.

- Weekly area under the curve (AUC) of the EASI score from baseline to the latest evaluable assessment before or on week 16 visit, use of rescue medication, loss to follow-up or withdrawal of consent, whichever occurs first.

- Weekly area under the curve (AUC) of the EASI score from baseline to the latest evaluable assessment before or on week 24 visit, use of rescue medication, loss to follow-up or withdrawal of consent, whichever occurs first.

- Time to new AD flare, defined as ≥ 50% worsening of Baseline EASI score or EASI score of > 21.0 (severe AD) from Baseline to end of the treatment period and the observational period.

- Difference in free of flares days between treatment groups (placebo vs. verum) from Baseline to the end of treatment period

- Number of new AD flares during the induction and maintenance period and during the whole treatment and observational period

- EASI score change during the induction and maintenance period and during the whole treatment period and the observational period.

SCORAD score change during the induction and maintenance period and during the whole treatment period and the observational period

- vIGA-AD (Validated Investigator Global Assessment in Atopic Dermatitis) score change during the induction and maintenance period and during the whole treatment period and the observational period

- ADCT score change during the induction and maintenance period and during the whole treatment period and the observational period

- Number and duration in days of TCS (Topical Corticosteroids) treatments for acute flares during the induction and maintenance period and during the whole treatment period and the observational period

- Incidence of skin infections requiring systemic treatment and antibiotics during the induction and maintenance period and during the whole treatment period and the observational period

- Number of respiratory tract infections and wheezing episodes during the induction and maintenance period and during the whole treatment period and the observational period

- Change of gut microbiome from Baseline to the end of the treatment period and to the observational period.

- Change of skin microbiome during the induction and maintenance period and during the whole treatment period and the observational period, incl. S. Aureus infections.

- Potential correlations between gut microbiome data and primary and/or secondary outcomes (e.g., EASI, SCORAD, vIGA-AD).

- Potential correlations between gut microbiome data and skin microbiome and primary and/or secondary outcomes (e.g. EASI, Scorad, vIGA-AD) data (using diversity measures for the skin microbiome)

- Optional: Change of total IgE ( Immunoglobulin E) and specific IgEs from Baseline to the end of the treatment period and the observational period

- Optional: Change in expression of disease biomarkers in blood from Baseline to the end of the treatment period and the observational period.

- Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events from Baseline to the end of the observational period

Potential correlations between skin microbiome data and primary and/or secondary outcomes (e.g., EASI, SCORAD, vIGA-AD)

Inclusion Criteria: Children of either gender, aged 3 to 24 months Patients with a clinically confirmed diagnosis of AD (according to Hanifin and Rajka) of moderate severity (EASI 7.1 - 21.0) and lesions covering up to 30% of the body either assessed by Investigator at the Screening/Baseline visit or recently (<4 weeks prior to Screening/Baseline visit) documented by Investigator and pre-treated with TCS (within last 4 weeks prior to Screening/Baseline visit). Atopic Dermatitis onset no longer than 12 months before Screening Legally acceptable representatives (i.e. parent(s) or guardians) of subject according to local regulations 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: Any diseases that may be considered as the differential diagnosis of atopic dermatitis, and notably skin infections and infestations (e.g. scabies), other inflammatory skin conditions, dermatological malignancies, dermatological genetic diseases such as immunodeficiency conditions, and nutritional disorders with cutaneous manifestations and drug eruptions. Specifically, any inflammatory skin conditions that are considered during the differential diagnosis of atopic dermatitis: allergic contact dermatitis, dermatographism, psoriasis, pityriasis alba. Any chronic diseases (other than wheezing and asthmatic bronchitis) that require the administration of systemic corticosteroids (e.g., eosinophilic esophagitis) or immunosuppressant agents. Significant medical condition(s), which, in the Investigator's opinion, are anticipated to require major surgery during the study, or any other type of disorder that might involve an increased risk to the subject, could interfere with study assessments or outcomes, or the ability of parents to comply with the study procedures (e.g. eDiary). Infants and children with known allergy or previous intolerance/sensitivity to any of the trial treatments (IMP, AxMP or standardized emollient) to be administered. Use of systemic drugs interfering with the immune system (e.g. corticosteroids, immunosuppressants) within 30 days before Baseline (with exception of routine vaccinations) Previous or ongoing treatment with other bacterial lysates and/or probiotics within 30 days before Baseline Use of systemic antibiotics within 30 days before Baseline Participation in any other investigational trial on a medical device or medicinal product <30 days prior to Baseline or any previous participation in a study involving bacterial lysates and/or probiotics, or current treatment with other investigational agent(s) Any major surgery within the last 3 months prior to Baseline, that in the opinion of the Investigator, would not allow safe completion of the clinical study. Subject's families expected to relocate out of study area during the duration of the study. Other household members have previously been randomised in this clinical study. Previous participation to this study. Close affiliation of subject or parents with the investigational site; e.g. a close relative of the Investigator, dependent person (e.g. employee or student of the investigational site)