Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations
Condition: Asthma
MeSH terms: Asthma
Intervention: Omalizumab; Inhaled Corticosteroid Boost Therapy (ICS); Placebo omalizumab; Placebo fluticasone
Intervention description: Participants received active omalizumab (Xolair(R)) injections and a placebo inhaler. Each participant received omalizumab (Xolair(R)) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) [IU/mL] every 2 or 4 weeks during the 4-5 months treatment period. All participants received standardized specialist asthma care.; Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone. All participants will receive standardized specialist asthma care.; Placebo was administered subcutaneously every 2 or 4 weeks over a period of 4 to 5 months. Doses (mg) and dosing frequency were determined by serum total immunoglobulin E (IgE) level (IU/mL) and body weight (kg). Also, participants continued with their conventional asthma therapy according to the National Asthma Education and Prevention Program (NAEPP, 2007) guidelines, under the management of an asthma specialist health care provider.; Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.
Intervention MeSH terms: Fluticasone; Xhance; Omalizumab; Antibodies, Monoclonal
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 478.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: persistent allergic asthma; asthma exacerbations reduction; Xolair® (omalizumab); Flovent® Diskus® (fluticasone); placebo; inhaled corticosteroid therapy; anti-immunoglobulin E therapy; anti-IgE therapy

Summary:

      The purpose of this trial is to compare the efficacy of 4 to 5 months of three treatments -
      omalizumab, corticosteroid therapy boost, and placebo - in reducing fall exacerbations in
      inner-city children and adolescents with allergic persistent asthma when initiated
      approximately 4 -6 weeks prior to the start of the first day of each participant's school
      year.
    

Eligibility criteria:

        Inclusion Criteria :

          -  Combined body weight (as measured at the screening visit) and total serum IgE level
             (as measured within 3 months of the screening visit) suitable for omalizumab (Xolair®)
             dosing;

          -  A diagnosis of asthma by a clinician made more than 1 year prior to recruitment;
             participants who received an asthma diagnosis by a clinician less than 1 year prior to
             recruitment must report that their respiratory symptoms were present for more than 1
             year prior to recruitment;

          -  Having a requirement for at least 100 mcg fluticasone 100 mcg twice a day or
             equivalent at the Assumption of Care Visit AND who meet at least one of the following
             criteria:

             i. ≥1 asthma-related exacerbations, separated by at least two weeks, requiring
             treatment with a systemic corticosteroid course in the previous 12 months ii. ≥1
             asthma-related overnight hospitalizations in the past 12 months.

          -  A positive prick skin-test to at least one perennial allergen (i.e. dust mite,
             cockroach, mold, cat, dog, rat, mouse) documented at the screening visit or at a ICAC
             study visit within 12 months of the screening visit;

          -  Primary place of residence is in one of the pre-selected recruitment census tracts;

          -  Able to perform spirometry;

          -  Parent or legal guardian is willing to sign the written informed consent (age
             appropriate) prior to initiation of any study procedure;

          -  Willing to sign the assent form, if age appropriate;

          -  A history of chickenpox or receipt of the chickenpox vaccine;

          -  Insurance which covers costs of medications; and

          -  Have not used and do not plan to restart any of the following medications in the 7
             days prior to the first visit: tricyclic antidepressants, ketaconazole, or beta
             adrenergic blocker drugs (oral and/or topical).

        Exclusion Criteria:

        Participants who meet any of the following criteria are not eligible for enrollment but may
        be reassessed:

          -  Assigned to a treatment of less than 100 mcg fluticasone twice a day or equivalent at
             the Assumption of Care Visit;

          -  Pregnant or lactating. Females of child-bearing potential (post-menarche) must be
             abstinent or use a medically acceptable birth control method throughout the study
             (e.g. oral, subcutaneous, mechanical, or surgical contraception);

          -  Clinically significant laboratory abnormalities (not associated with the study
             indication) at the screening visit;

          -  Platelet count less than 100 x 10^9/L at the screening visit;

          -  Currently participating in another asthma-related pharmaceutical study or intervention
             study or who have participated in another asthma-related pharmaceutical study or
             intervention study in the month prior to Recruitment;

          -  Living with a foster parent: exception -not applicable if participant is able to
             provide consent;

          -  Does not have access to a phone (needed for scheduling appointments);

          -  Plan(s) to move from the area during the study period;

          -  Has previously been treated with omalizumab (Xolair®) within 1 year of recruitment;

          -  Currently receiving or has received hyposensitization therapy to any allergen in the
             past year prior to recruitment;

          -  Has received hyposensitization therapy to dust mite, Alternaria or cockroach for ≥ 6
             months in the past 3 years prior to Recruitment;

          -  Has experienced a life-threatening asthma exacerbation in the last 2 years requiring
             intubation, mechanical ventilation, or resulting in a hypoxic seizure;

          -  Home-schooled or in year round school;

          -  Are currently taking or who have taken any of the following medications within 4 weeks
             of the Screening Visit: monoamine oxidase inhibitors (phenelzine, tranylcypromine);
             tricyclic and tetracyclic antidepressants; beta adrenergic blocker drugs (both oral
             and topical); anticonvulsants(carbamazepine, phenobarbital, phenytoin, mephobarbital,
             primidone,ethosuximide, methsuximide, felbamate, gabapentin, lamotrigine,
             levetiracetam, oxcarbazepine, tiagabine, topiramate, valproic acid, divalproex sodium,
             zonisamide); protease inhibitors(ritonavir, indinavir, nelfinavir); calcium channel
             blockers (verapamil, diltiazem); modafinil; tamoxifen; non-nucleoside reverse
             transcriptase inhibitors; macrolide antibiotics*(erythromycin, clarithromycin,
             dirithromycin, troleandomycin); chloramphenicol; nefazodone; aprepitant; St. John's
             Wort (hypericum); Rifampin*; Azole antifungals* (ketoconazole,
             fluconazole,itraconazole); Sibutramine*; bergamottin* (constituent of grapefruit
             juice).*may be rescreened if this therapy is short-lived;

          -  Will not allow the study clinician, an asthma specialist, to manage their disease for
             the duration of the study or who are not willing to change their asthma medications to
             follow the protocol.

        Participants who meet any of the following criteria are not eligible for assumption of care
        and may not be reassessed except where noted:

          -  A current severe hypersensitivity to milk;

          -  Individuals who were enrolled in the previous ICAC trial, Inner-City Anti-IgE Therapy
             for Asthma (ICATA,ICAC-NCT00377572);

          -  Individuals who have any medical illnesses that in the opinion of the investigators
             would a.) increase the risk the subject would incur by participating in the study; b.)
             interfere with the measured outcomes of the study; or c.) interfere with the
             performance of the study procedures. Examples of such diseases are: cystic fibrosis,
             bronchiectasis, type 1 diabetes, hemophilia, Von Willebrand disease, sickle cell
             disease, cerebral palsy, rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E
             syndrome, parasite infections, Wiskott-Aldrich Syndrome or allergic bronchopulmonary
             aspergillosis.

          -  Known hypersensitivity to any ingredients, including excipients (sucrose, histidine,
             polysorbate 20) of the study medication or drugs related to omalizumab (e.g.
             monoclonal antibodies, polyclonal gamma globulin) or fluticasone;

          -  Currently have diagnosed cancer, are currently being investigated for possible cancer,
             or who have a history of cancer;

          -  Do not primarily speak English (or Spanish at centers with Spanish speaking staff)

          -  The participant's caretaker does not primarily speak English (or Spanish at centers
             with Spanish speaking staff); not applicable if participant is able to provide
             consent.

          -  A history of severe(grade 3) anaphylactoid or anaphylactic reaction(s).