Clinical trial NCT01430403: Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations
Official title: Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (ICAC-20)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: persistent allergic asthma
asthma exacerbations reduction
Xolair® (omalizumab)
Flovent® Diskus® (fluticasone)
placebo
inhaled corticosteroid therapy
anti-immunoglobulin E therapy
anti-IgE therapy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Inner-City Asthma Consortium
First posted: 2011-09-08
Enrollment: 478
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: While the increase in the prevalence of asthma has abated, levels of asthma morbidity and mortality remain near record highs. An asthma exacerbation is a major factor contributing to morbidity, and even mortality in patients with asthma. Although current approaches to treatment have reduced these risks, asthma exacerbations are major problems for inner-city patients and their families, and prevention of these events continues to be a significant challenge. In children with asthma, there are predictable seasonal epidemics of exacerbations, especially during the fall season, otherwise known as the "September epidemic."

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).

Primary outcomes:
measure: Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])
timeFrame: 90 Day outcome period
measure: Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)
timeFrame: 90 Day outcome period
Secondary outcomes:
measure: Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples
timeFrame: 90 Day outcome period
measure: Severity of Asthma Symptoms Associated With a Viral Infection:Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Number of Exacerbations Evaluated Monthly With Viral Respiratory Infections: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Composite Asthma Severity Index (CASI), Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Composite Asthma Severity Index (CASI), Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted, Treatment Steps 2-5:Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted , Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Work Disruptions Due to Child's Asthma, Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Work Disruptions Due to Child's Asthma, Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: School Absences (Percent), Treatment Steps 2-5:Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: School Absences (Percent), Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Percent Adherence to Asthma Medication, Treatment Steps 2-5: Omalizumab vs. Placebo
timeFrame: 90 Day outcome period
measure: Percent Adherence to Asthma Medication, Treatment Steps 2-4: Omalizumab vs. ICS
timeFrame: 90 Day outcome period
measure: Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo
timeFrame: 90 Day outcome period
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Department of Allergy
state: Illinois
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: National Jewish Health
name: Stanley Szefler, MD
role: STUDY_CHAIR
affiliation: Children's National Research Institute
name: Stephen Teach, MD, MPH
role: STUDY_CHAIR
References:
citation: Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, Wildfire JJ, Gergen PJ, Cohen RT, Pongracic JA, Kercsmar CM, Khurana Hershey GK, Gruchalla RS, Liu AH, Zoratti EM, Kattan M, Grindle KA, Gern JE, Busse WW, Szefler SJ. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015 Dec;136(6):1476-1485. doi: 10.1016/j.jaci.2015.09.008. Epub 2015 Oct 27.
citation: Szefler SJ, Casale TB, Haselkorn T, Yoo B, Ortiz B, Kattan M, Busse WW. Treatment Benefit with Omalizumab in Children by Indicators of Asthma Severity. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2673-2680.e3. doi: 10.1016/j.jaip.2020.03.033. Epub 2020 Apr 13.
citation: Esquivel A, Busse WW, Calatroni A, Togias AG, Grindle KG, Bochkov YA, Gruchalla RS, Kattan M, Kercsmar CM, Khurana Hershey G, Kim H, Lebeau P, Liu AH, Szefler SJ, Teach SJ, West JB, Wildfire J, Pongracic JA, Gern JE. Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma. Am J Respir Crit Care Med. 2017 Oct 15;196(8):985-992. doi: 10.1164/rccm.201701-0120OC.