Omalizumab Before Onset of Exacerbations
OBOE is a prospective, pilot, parallel group RCT with the overall aim of examining the effect of a single dose of anti-IgE (omalizumab) vs. placebo administered at the onset of URIs in the fall season among highly exacerbation-prone, urban, and atopic youth aged 6-17 years with persistent asthma. OBOE will recruit and randomize participants over 3 years (3 annual cohorts of participants). Recruitment for each of the yearly cohorts of OBOE will begin in February. Each cohort will be followed for a 2-6-month run-in period with the objective to gain control of each participant's asthma and to stabilize the required controller medication step level. Participants will receive routine asthma care every 1-2 months (a total of 2-4 times) during run-in using a previously described algorithm developed by the Inner-city Asthma Consortium and successfully employed in the PROSE study. The primary outcome is the change in the amount of nasal IFN-α recovered by nasal fluid absorption between two time points, within 72 hours of onset of a URI as defined by onset of (or substantial worsening of) rhinorrhea, nasal congestion or sneezing (single or multiple symptoms) and 3-6 days after study drug injection.
• Participants must meet the following:
• Parent or guardian must be able to understand and provide informed consent in English and participants ≥7 must be able to provide assent
• 6-17 years, inclusive at time of screening
• Physician-diagnosed persistent asthma
• ≥1 exacerbation of asthma requiring systemic corticosteroids in the 6-month period before the planned start of the participant's upcoming school year or ≥2 exacerbations of asthma requiring systemic corticosteroids in the 12-month period before the planned start of the participant's upcoming school year
• Sensitization to ≥1 perennial aeroallergen
• Total serum IgE and weight appropriate for omalizumab dosing
• Insurance that covers standard of care medications
• Primary family residence (home where child sleeps a majority of nights) in a Metropolitan Statistical Area where ≥10% of families have income below poverty line and/or publicly funded health insurance
• At least one of the following criteria:
∙ peripheral eosinophilia \>300µL
‣ total serum IgE \>300kU/L
‣ sensitization to ≥3 perennial aeroallergens
⁃ Females of childbearing potential must have a negative pregnancy test upon study entry
⁃ Females with reproductive potential must agree to use FDA approved methods of birth control for the duration of the study
• Additional Inclusion Criteria (these must be met prior to randomization at the fall season sick visit A (SVa) during the 90-day outcome period):
• In order to be eligible for randomization at the SVa visit, participants must also meet all of the following criteria:
• Reporting onset of URI symptoms within 72 hours prior to SVa, confirmed by the study physician
• Report no use of nasal corticosteroids or nasal vaccinations within 14 days prior to SVa
• Have a negative rapid nasal swab antigen test for SARS-CoV-2
• Be more than 14 days from the onset of any previous asthma exacerbation requiring systemic steroids
• Have no current lower respiratory symptoms that, in the opinion of the study physician, require systemic corticosteroid treatment
• Complete collection of nasal absorption sample within 72 hours of onset URI \[defined by onset of (or substantial worsening of) rhinorrhea, nasal congestion or sneezing (single or multiple symptoms)\] as determined by the study physician's assessment at the SVa visit