Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations
Study Synopsis for the Institutional Review Boards
PROSE is a three-arm, randomized, double-blind, placebo-controlled trial that will investigate the efficacy of two drug therapies in reducing fall exacerbations in inner-city children and adolescents aged 6 to 17 years with persistent allergic asthma. A total of 453 participants across nine study sites will be randomized to receive 1) omalizumab (Xolair[RegisteredTM]), which is an anti-IgE agent, plus an inhaled corticosteroid placebo, 2) inhaled corticosteroid boost therapy (fluticasone, Flovent[RegisteredTM] Diskus[RegisteredTM]) plus an omalizumab placebo, or 3) omalizumab placebo and an inhaled corticosteroid placebo. All participants will receive standard asthma care by study clinicians in addition to their randomized therapies. Treatment will be initiated one month prior to the start of a fall viral season and will last four to five months. Prior to the treatment period, participants will undergo a five- to nine-month stabilization phase during which their asthma care will be optimized by study clinicians. The study will be conducted over two consecutive fall seasons with a different group of participants in each fall season. Potential participants will be consented and screened during fall and winter months of two consecutive years. Approximately 1000 persons will have to be consented and screened in order to have 533 persons eligible for the stabilization phase and 453 persons eligible for randomization. The duration of the trial is approximately 29 months and the duration of a subject's participation is 13-16 months. Both study drugs, Xolair[RegisteredTM] and Flovent[RegisteredTM] Diskus[RegisteredTM], are approved and marketed for the treatment of asthma, and adverse reactions to these drugs have been well described. Xolair[RegisteredTM] has not been approved for children [Less Than]12 years of age and the planned dosage regimens of Flovent[RegisteredTM] Diskus[RegisteredTM] have not been approved for that age group; however, previous studies have administered Xolair[RegisteredTM] to children [Less Than]12 years of age and the planned dosage regimens of Flovent[RegisteredTM] Diskus[RegisteredTM] are consistent with approved asthma management guidelines and are widely prescribed to this age group. This trial is regulated by the U.S. Food and Drug Administration and will be conducted under an existing Investigational New Drug application. Benefits to the participants from this trial include frequent asthma assessments and asthma care provided by study clinicians. The primary outcome, which will be assessed from September to November of each fall season, is at least one asthma exacerbation severe enough to require initiation of systemic steroid therapy or a hospitalization during the fall outcome period. Statistical analyses will test whether the incidence of a fall exacerbation differs between participants in the omalizumab and placebo arms and between subjects in the omalizumab and inhaled corticosteroid boost arms.
Participants who meet all of the following criteria are eligible for assumption of care. Participants may be reassessed if not initially eligible.
1. Males and females ages 6 x 17 years, inclusive, at Screening (V0).
2. With combined body weight [as measured at the Screening visit (V0)] and total serum IgE level [as measured within 3 months of the Screening Visit (V0)] suitable for omalizumab (Xolair(RegisteredTM)) dosing.
3. Who have had a diagnosis of asthma by a clinician made > 1 year prior to Recruitment; participants who received an asthma diagnosis by a clinican <= 1 year prior to recruitment, must
report that their respiratory symptoms were present for more than 1 year prior to recruitment.
4. Who have a requirement for at least Step Level 2 therapy (defined in Table 5.5.1b) at the Assumption of Care Visit (V1) and who meet at least one of the following criteria:
i. One or more asthma-related exacerbations, separated by at least 2 weeks, requiring treatment with a systemic corticosteroid course which occurred on or after September 1, 2010, for the
first cohort or on or after September 1, 2011, for the second cohort.
ii. One or more asthma-related overnight hospitalizations, which occurred on or after September
1, 2010, for the first cohort or on or after September 1, 2011, for the second cohort
5. With a positive prick skin-test to at least 1 perennial allergen (as outlined in the PROSE MOP) documented at the Screening Visit (V0) or at any ICAC study visit within 12 months of the Screening Visit (V0).
6. Whose primary place of residence is in one of the pre-selected recruitment census tracts as outlined in the PROSE MOP.
7. Who are able to perform spirometry at the Assumption of Care Visit (V1).
8. Who are willing to sign the written Informed Consent or whose parent or legal guardian is willing to sign the written Informed Consent (age appropriate) prior to initiation of any study procedure.
9. Who are willing to sign the assent form, if age appropriate.
10. Who have a self-reported history of clinical varicella or administration of varicella vaccine.
11. Who have some form of insurance that covers costs of medications at the Screening Visit (V0).