Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness

This is a 36 month parallel arm, double-blind, placebo-controlled trial for the prevention of
WLRI into the third to fifth year of life (30 to 54 mo inclusive) in young children (6-18
months old) at increased risk for asthma. The trial will be divided into 2 periods. During
the initial treatment period (first and second years in the study) participants will receive
Broncho-Vaxom® (3.5 mg) or placebo for ten days each month for two consecutive years. This
period will allow the observation of key secondary outcomes while participants are receiving
therapy. A rolling enrollment strategy will be used anticipating a two year enrollment period
for the whole study. The second period (third year in the study) will be a one year
observation of the time to occurrence of the first WLRI episode (primary outcome) while off
study drug along with the secondary outcomes noted above. During both the treatment and
observation periods, participants will be managed by study physicians using a rescue
algorithm applied in the PEAK (Prevention of Early Asthma in Kids) trial commensurate with
the NAEPP-EPR (National Asthma Education and Prevention Program - Expert Panel Report) III
guidelines.

Inclusion Criteria:

- Adequate completion of informed consent process with written documentation. The
participant's legally acceptable representative must have provided the appropriate
written informed consent. Assent forms will not be used due to the age of the
participant population; however, for procedures later in the study when participants
are older, age appropriate assent will be obtained, if required by local IRB.

- Age: 6-18 months of age inclusive at randomization which means 5 to 17 months of age
inclusive on entry into the one month run-in period. At least half of all enrolled
children will be between 6 and 12 months of age at randomization.

- Participants will meet at least one of the following criteria, which have been
associated with an increased risk of wheezing respiratory illnesses and asthma: a)
Parental history of asthma -or- b) Physician-diagnosed atopic dermatitis in the
participant - or- c) Physician-diagnosed asthma in a blood sibling aged 4 years or
more.

- Participants may be either male or female.

- Participants will have at least one parent/guardian who can communicate with the study
staff to allow assessment of study outcomes. All study materials used by
parent/guardian will be made available in English and in Spanish.

The child's parent/guardian must have a working direct contact telephone.

Exclusion Criteria:

- Participants may not have had more than two prior WLRI episodes.

- Participants may not have had any SWLRI episodes.

- Participants may not have a physician's diagnosis of asthma.

- Participants may not have a systemic illness (other than allergy) including (but not
limited to) recurrent seizures, chronic gastroesophageal reflux (GER) requiring
medical treatment, major congenital anomalies, physical and intellectual delay,
cerebral palsy, chest surgery, tuberculosis or other chronic infections, primary or
secondary immunodeficiency, gastrointestinal malformation or disease or cardiac
disorder (except a hemodynamically insignificant ASD, VSD or benign heart murmur).

- Participants may not have been born earlier than 36 weeks of gestation.

- Participants may not have received oxygen for more than 5 days in the neonatal period,
or received mechanical ventilation with the exclusion of ventilation during anesthesia
for a minor surgical procedure.

- Participants may not have significant neurodevelopmental delay.

- Participants may not be below the 3rd percentile for weight.

- Participants may not have any other chronic lung disease; e.g. chronic lung disease of
prematurity (CLDP) or cystic fibrosis.

- Participants may not have a history of any life-threatening respiratory illness that
required intubation and mechanical ventilation.

- The participant's family may not be expected to relocate out of study area within 3
years of the initiation of the study.

- Participants may not have received inhaled or systemic corticosteroids for respiratory
related illness ever, or for other conditions in the month prior to randomization.

- Participants may not have ever received immunotherapy.

- Participants may not have ever received i.v. gammaglobulins or systemic
immunosuppressants.

- Participants may not have received probiotics (Lactobacilli and Bifidobacteria) in
medicinal form; (i.e. not including food), regularly for more than 4 months in the 6
to <12 mo age group or 6 months in the 12 to 18 month group prior to enrollment.

- Participant has known sensitivity to any of the study products and any of the
ingredients to be administered.

- Participant has previously been randomized in this study. Participants who failed
run-in and were not randomized may have study participation terminated and then be
re-enrolled for a second run-in period.

- Participant is currently enrolled in or has completed any other investigational device
or drug study <30 days prior to screening, or is receiving other investigational
agent(s).

- Participant has a significant medical condition(s), anticipated need for major surgery
during the study, or any other kind of disorder that may be associated with increased
risk to the participant, or may interfere with study assessments, outcomes, or the
ability to provide written informed consent or comply with study procedures, in the
Investigator's opinion.

- The one month run-in period will be used to evaluate adherence to study drug
administration and electronic communication. At randomization the participant must
continue to meet enrolment criteria and also have demonstrated 80% adherence to the
placebo during treatment period; i.e. 8 out of 10 days and a75% response rate to
weekly mobile phone text queries; i.e. 3 out of 4 weekly text queries.

- Ongoing infection (of any organ system) at the time of randomization. This includes
infections that are being adequately treated.

- Unable or unlikely to complete study assessments or the study intervention poses undue
risk to patient in the opinion of the Investigator.

- Families will speak English and/or Spanish.