Preventative Omalizumab or Step-up Therapy for Severe Fal... | NCT01430403

Name	Class
Inner-City Asthma Consortium	NETWORK

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Omalizumab	Experimental	Participants receive active omalizumab (Xolair®) injections and a placebo Flovent® Diskus® (fluticasone) inhaler. Each participant will receive omalizumab (Xolair®) 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. In addition, all participants receive standardized specialist asthma care.	Biological: Omalizumab Biological: Placebo fluticasone
Inhaled Corticosteroid Boost Therapy (ICS)	Experimental	Participants in this group, the Inhaled Corticosteroid (ICS) boost arm, receive active ICS and placebo omalizumab (Xolair®) injections. Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone will be used. In addition, all participants receive standardized specialist asthma care.	Drug: Inhaled Corticosteroid Boost Therapy (ICS) Biological: Placebo omalizumab
Placebo	Placebo Comparator	The placebo group receive placebo omalizumab (Xolair®) injections and placebo Flovent® Diskus® (fluticasone) inhaler. In addition, all participants receive standardized specialist asthma care.	Biological: Placebo omalizumab Biological: Placebo fluticasone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Omalizumab	Biological	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])	Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Placebo and Omalizumab arms across all treatment steps (Steps 2-5).	90 Day outcome period
Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)	Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Inhaled corticosteroid boost therapy (ICS) and Omalizumab arms at Treatment Steps 2-4.	90 Day outcome period

Secondary Outcomes

Measure	Description	Time Frame
Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples	Asthma exacerbation:defined by a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the 1st day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥ 10mg per day for ≥1 day. Exacerbations were then associated with viral respiratory infections based on nasal mucus samples collected monthly. Nasal mucus samples were categorized as having exacerbations or not having exacerbations. Participants could potentially be counted in each group, as participants could have samples with exacerbations and samples without exacerbations.

Eligibility Module

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).

Name	Affiliation	Role
Stanley Szefler, MD	National Jewish Health	Study Chair
Stephen Teach, MD, MPH	Children's National Research Institute	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
National Jewish Health		Denver	Colorado	80206	United States
Children's National Medical Center

PubMed Identifier	Type	Citation	Retractions
26518090	Result	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.
32298853

Label	URL
Division of Allergy, Immunology, and Transplantation (DAIT) website	View source

ID	Title	Description
FG000	Omalizumab	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])

Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Placebo and Omalizumab arms across all treatment steps (Steps 2-5).

Intent-to-treat

Posted

Number

Percent of adjusted prevalence

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Units	Counts
Participants	OG000259 OG00189

Title

Denominators

Categories

Title	Measurements
	OG00011.3 OG00121.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis is that there is no difference between the arms. Power calculation is described in detail in the study protocol.	Odds Ratio	Adjusted for Site, dosing group and treatment step	0.03		Odds Ratio (OR)	0.48	Standard Error of the Mean	0.331	2-Sided	95	0.25	0.92			Placebo serves as the reference group. Values < 1 represent more exacerbations in the placebo arm.		Superiority or Other

Primary

Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)

Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Inhaled corticosteroid boost therapy (ICS) and Omalizumab arms at Treatment Steps 2-4.

Intent-to-treat

Posted

Number

Percent of adjusted prevalence

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples

Asthma exacerbation:defined by a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the 1st day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥ 10mg per day for ≥1 day. Exacerbations were then associated with viral respiratory infections based on nasal mucus samples collected monthly. Nasal mucus samples were categorized as having exacerbations or not having exacerbations. Participants could potentially be counted in each group, as participants could have samples with exacerbations and samples without exacerbations.

Nasal mucus samples

Posted

Number

Percent Samples with virus

90 Day outcome period

Number of Samples Analyzed

ID	Title	Description
OG000	Samples With Exacerbations	These nasal mucus samples were associated with an exacerbation (defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at >/= 20mg per day for 3 of any 5 consecutive days; or dexamethasone at >/= 10mg per day for >/= 1 day)

Secondary

Severity of Asthma Symptoms Associated With a Viral Infection:Omalizumab vs. Placebo

Severity asthma symptoms is defined as the highest value among the following 3 variables: number of days with wheezing, tightness in the chest, or cough; number of nights with disturbed sleep as a result of asthma; and number of days on which a participant had to slow down or discontinue play/physical activities over a two week period associated with a viral infection. This outcome looks at the effect by group on number of days with asthma symptoms and infections. The hypothesis behind this outcome measure is that omalizumab will change virology; thus, the the intent of this measure was to assess the comparator group of placebo against omalizumab

The pre-specified intent for Outcome Measure: analysis inclusion limited to the Omalizumab and Placebo Groups.

Analysis: intent-to-treat (with available data).

Posted

Mean

Standard Error

Maximum Symptoms Days

90 Day outcome period

ID	Title	Description
OG000	Omalizumab	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.
OG001	Placebo	Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.

Secondary

Number of Exacerbations Evaluated Monthly With Viral Respiratory Infections: Omalizumab vs. Placebo

Asthma exacerbation is defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. The hypothesis behind this outcome measure is that omalizumab will change virology; thus, the intent of this measure was to assess the comparator group of placebo against omalizumab.

The pre-specified intent for Outcome Measure: analysis inclusion limited to the Omalizumab and Placebo Groups.

Analysis: intent-to-treat (with available data).

Posted

Mean

Standard Error

Total Number of Viral Infections

90 Day outcome period

ID	Title	Description
OG000	Omalizumab	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.
OG001	Placebo

Secondary

Composite Asthma Severity Index (CASI), Treatment Steps 2-5: Omalizumab vs. Placebo

CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. To calculate CASI, the 5 domain scores are summed to determine a final score, which can range from 0 to 20, with 0 being no severity of asthma and 20 being extremely severe asthma.

Intent-to-treat

Posted

Mean

Standard Error

CASI Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Composite Asthma Severity Index (CASI), Treatment Steps 2-4: Omalizumab vs. ICS

Intent-to-treat with available CASI scores

Posted

Mean

Standard Error

CASI Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted, Treatment Steps 2-5:Omalizumab vs. Placebo

FEV1 is air volume exhaled in 1 second during spirometry. Asthma severity classification for trial: mild--pre-bronchodilator FEV1 ≥ 80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; moderate--pre-bronchodilator FEV1 <80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; severe--requiring high-dose inhaled glucocorticoids with/without continuous/near continuous oral glucocorticoids, or uncontrolled despite treatment. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race.

Intent-to-treat

Posted

Mean

Standard Error

percent predicted FEV1

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted , Treatment Steps 2-4: Omalizumab vs. ICS

Intent-to-treat

Posted

Mean

Standard Error

percent predicted FEV1

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-5: Omalizumab vs. Placebo

The FEV1 (forced expiratory volume 1))/ FVC (forced vital capacity) ratio is used to evaluate airways obstructions since pure restrictive ventilatory defects cause an equal reduction in the FEV1 and the FVC. An FEV1/FVC ratio below 80% indicates airflow obstruction. Normal FEV1/FVC: 8 - 19 years of age=85%.

Intent-to-treat

Posted

Mean

Standard Error

percent FEV1/FVC ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-4: Omalizumab vs. ICS

Intent-to-treat

Posted

Mean

Standard Error

percent FEV1/FVC ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-5: Omalizumab vs. Placebo

Outcome measure description: The Asthma Control Test (ACT) is a validated tool to assess asthma control (over the last 4 weeks) in patients ≥12 yrs old. It is comprised of 5 questions assessing symptoms, use of rescue medications, and the impact of asthma on everyday functioning. All questions are scored on a 5-point Likert scale (higher score indicating better control). Total scores can range from 5-25. A score of ≤19 is indicative of not well-controlled asthma. The minimally important difference is 3 points.

Intent-to-treat with available ACT scores

Posted

Mean

Standard Error

ACT Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-4: Omalizumab vs. ICS

The Asthma Control Test (ACT) is a validated tool to assess asthma control (over the last 4 weeks) in patients ≥12 yrs old. It is comprised of 5 questions assessing symptoms, use of rescue medications, and the impact of asthma on everyday functioning. All questions are scored on a 5-point Likert scale (higher score indicating better control). Total scores can range from 5-25. A score of ≤19 is indicative of not well-controlled asthma. The minimally important difference is 3 points.

Intent-to-treat with available ACT Scores

Posted

Mean

Standard Error

ACT Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-5: Omalizumab vs. Placebo

The Childhood Asthma Control Test (C-ACT) is a validated tool to assess overall asthma control (over the last 4 weeks) in patients ages 4 to 11 years. Scores can range from 0 to 27. A score of 19 or less is indicative of asthma that is not well controlled. The minimally important difference in C-ACT scores is not defined

Intent-to-treat with available C-ACT Scores

Posted

Mean

Standard Error

C-ACT Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-4: Omalizumab vs. ICS

Intent-to-treat with available C-ACT Scores

Posted

Mean

Standard Error

C-ACT Score

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Work Disruptions Due to Child's Asthma, Treatment Steps 2-5: Omalizumab vs. Placebo

The ratio of the work hours missed due to child's asthma over the numbers of work hours in the past 14 days among caretakers working.

Intent-to-treat with available data

Posted

Mean

Standard Error

Ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Units

Secondary

Work Disruptions Due to Child's Asthma, Treatment Steps 2-4: Omalizumab vs. ICS

The ratio of the work hours missed due to child's asthma over the numbers of work hours in the past 14 days among caretakers working

Intent-to-treat with available data

Posted

Mean

Standard Error

Ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

School Absences (Percent), Treatment Steps 2-5:Omalizumab vs. Placebo

The ratio of the number of school days missed over the numbers of school days in session

Intent-to-treat

Posted

Mean

Standard Error

Ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Units	Counts

Secondary

School Absences (Percent), Treatment Steps 2-4: Omalizumab vs. ICS

The ratio of the number of school days missed over the numbers of school days in session

Intent-to-treat

Posted

Mean

Standard Error

Ratio

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Units	Counts

Secondary

Percent Adherence to Asthma Medication, Treatment Steps 2-5: Omalizumab vs. Placebo

Adherence to the study regimen and other asthma treatments, assessed as percent of expected dose taken, by means of study interviews and study physician corroboration.

Intent-to-treat

Posted

Mean

Standard Error

percent adherence

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-5: Omalizumab	Participants on the omalizumab arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-5: Placebo	Participants on the placebo arm across all treatment steps (2-5) at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Percent Adherence to Asthma Medication, Treatment Steps 2-4: Omalizumab vs. ICS

Adherence to the study regimen and other asthma treatments, assessed as percent of expected dose taken, by means of study interviews and study physician corroboration.

Intent-to-treat

Posted

Mean

Standard Error

percent adherence

90 Day outcome period

ID	Title	Description
OG000	Treatment Steps 2-4: Omalizumab	Participants on the omalizumab arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.
OG001	Treatment Steps 2-4:Inhaled Corticosteroid Boost Therapy (ICS)	Participants on the ICS arm at Treatment Steps 2-4 at randomization. Six treatment steps were established, consistent with report 3 of the National Asthma Education and Prevention Program guidelines to standardize prescribing patterns according to levels of asthma severity. Steps 1 and 2 apply to mild asthma, Step 3 to moderate asthma, and Steps 4 through 5 to severe asthma.

Secondary

Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo

Residential environmental exposure to cockroach allergen of participants in the context of the risk of asthma exacerbations and effect of omalizumab versus placebo (control) on asthma exacerbations was explored. Presence of cockroach allergen in household dust samples was assessed. Exacerbation defined as: participant required either 1.)a prescribed course of systemic steroids by a clinician2.)initiation of a course of systemic steroids or 3.)a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. In cases that a participant initiated and completed a course of systemic steroids without clinician involvement, the course was counted as an exacerbation only with fulfillment of the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day).

Prespecified Outcome Measure: analysis limited to the Omalizumab and Placebo Groups.

Analysis: intent-to-treat (with available data).

Posted

Count of Participants

Participants

90 Day outcome period

ID	Title	Description
OG000	Omalizumab	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaphylactic reaction	Immune system disorders	MedDRA 10.0	Systematic Assessment		EG0000 events0 affected259 at risk EG0011 events1 affected130 at risk EG0020 events0 affected89 at risk
VIIth nerve paralysis	Nervous system disorders	MedDRA 10.0	Systematic Assessment		EG0000 events0 affected259 at risk EG0010 events0 affected130 at risk EG0021 events1 affected89 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00013 events10 affected259 at risk EG0019 events8 affected130 at risk EG0023 events3 affected89 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00018 events17 affected259 at risk EG0015 events4 affected130 at risk EG0027 events6 affected89 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00016 events16 affected259 at risk EG0015 events5 affected130 at risk EG0024 events4 affected89 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D000888	Antibodies, Anti-Idiotypic
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Omalizumab	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.
BG001	Inhaled Corticosteroid Boost Therapy (ICS)	Participants in the Inhaled Corticosteroid (ICS) boost arm received active ICS and placebo injections of omalizumab (Xolair(R)). Self-administered fluticasone (Flovent (R) Diskus) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone were used. All participants received standardized specialist asthma care.
BG002	Placebo	Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Omalizumab	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.	259	0	259	41	259
EG001	Inhaled Corticosteroid Boost Therapy (ICS)	Participants in the Inhaled Corticosteroid (ICS) boost arm received active ICS and placebo injections of omalizumab (Xolair(R)). Self-administered fluticasone (Flovent (R) Diskus) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone were used. All participants received standardized specialist asthma care.	130	1	130	16	130
EG002	Placebo	Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.	89	1	89	12	89