Trial Outcomes & Findings for Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (NCT NCT01430403)

NCT ID: NCT01430403

Last Updated: 2017-05-30

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 478 participants
• Primary outcome timeframe: 90 Day outcome period
• Results posted on: 2017-05-30

Participant Flow

Eight National Institute of Allergy and Infectious Diseases (NIAID) Inner-City Asthma Consortium (ICAC) sites in the United States recruited the targeted number of study participants who fulfilled entry criteria. Recruitment occurred September 2011 to March 2014.

Participant milestones

Measure	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.	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.	Placebo Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.
Overall Study STARTED	259	130	89
Overall Study COMPLETED	242	121	81
Overall Study NOT COMPLETED	17	9	8

Reasons for withdrawal

Measure	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.	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.	Placebo Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.
Overall Study Lost to Follow-up	5	5	3
Overall Study Physician Decision	1	0	0
Overall Study Protocol Violation	2	3	2
Overall Study Withdrawal by Subject	9	1	3

Baseline Characteristics

Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations

Baseline characteristics by cohort

Measure	Omalizumab n=259 Participants 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.	Inhaled Corticosteroid Boost Therapy (ICS) n=130 Participants 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.	Placebo n=89 Participants Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.	Total n=478 Participants Total of all reporting groups
Age, Categorical <=18 years	259 Participants n=5 Participants	130 Participants n=7 Participants	89 Participants n=5 Participants	478 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized 6-11 years	190 participants n=5 Participants	102 participants n=7 Participants	67 participants n=5 Participants	359 participants n=4 Participants
Age, Customized 12-17 years	69 participants n=5 Participants	28 participants n=7 Participants	22 participants n=5 Participants	119 participants n=4 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	60 Participants n=7 Participants	30 Participants n=5 Participants	175 Participants n=4 Participants
Sex: Female, Male Male	174 Participants n=5 Participants	70 Participants n=7 Participants	59 Participants n=5 Participants	303 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	88 Participants n=5 Participants	43 Participants n=7 Participants	30 Participants n=5 Participants	161 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	171 Participants n=5 Participants	87 Participants n=7 Participants	59 Participants n=5 Participants	317 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	152 Participants n=5 Participants	82 Participants n=7 Participants	57 Participants n=5 Participants	291 Participants n=4 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	18 Participants n=7 Participants	9 Participants n=5 Participants	64 Participants n=4 Participants
Race (NIH/OMB) More than one race	27 Participants n=5 Participants	12 Participants n=7 Participants	9 Participants n=5 Participants	48 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	16 Participants n=7 Participants	11 Participants n=5 Participants	63 Participants n=4 Participants
Region of Enrollment United States	259 participants n=5 Participants	130 participants n=7 Participants	89 participants n=5 Participants	478 participants n=4 Participants

PRIMARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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).

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])	11.3 Percent of adjusted prevalence	21.0 Percent of adjusted prevalence

PRIMARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=121 Participants 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.	Treatment Steps 2-5: Placebo n=130 Participants 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.
Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)	8.4 Percent of adjusted prevalence	11.1 Percent of adjusted prevalence

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: 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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=149 Number of Samples Analyzed 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.	Treatment Steps 2-5: Placebo n=5061 Number of Samples Analyzed 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.
Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples	71.8 Percent Samples with virus	40.4 Percent Samples with virus

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: The pre-specified intent for Outcome Measure: analysis inclusion limited to the Omalizumab and Placebo Groups. Analysis: intent-to-treat (with available data).

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

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Severity of Asthma Symptoms Associated With a Viral Infection:Omalizumab vs. Placebo	1.2 Maximum Symptoms Days Standard Error 0.09	1.8 Maximum Symptoms Days Standard Error 0.23

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: The pre-specified intent for Outcome Measure: analysis inclusion limited to the Omalizumab and Placebo Groups. Analysis: intent-to-treat (with available data).

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=163 Participants 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.	Treatment Steps 2-5: Placebo n=65 Participants 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.
Number of Exacerbations Evaluated Monthly With Viral Respiratory Infections: Omalizumab vs. Placebo	5.6 Total Number of Viral Infections Standard Error 0.19	5.8 Total Number of Viral Infections Standard Error 0.13

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Composite Asthma Severity Index (CASI), Treatment Steps 2-5: Omalizumab vs. Placebo	4.9 CASI Score Standard Error 0.15	5.5 CASI Score Standard Error 0.27

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available CASI scores

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=82 Participants 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.	Treatment Steps 2-5: Placebo n=101 Participants 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.
Composite Asthma Severity Index (CASI), Treatment Steps 2-4: Omalizumab vs. ICS	4.6 CASI Score Standard Error 0.23	4.8 CASI Score Standard Error 0.24

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted, Treatment Steps 2-5:Omalizumab vs. Placebo	92.2 percent predicted FEV1 Standard Error 0.79	92.5 percent predicted FEV1 Standard Error 1.38

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=121 Participants 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.	Treatment Steps 2-5: Placebo n=130 Participants 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.
Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted , Treatment Steps 2-4: Omalizumab vs. ICS	93.2 percent predicted FEV1 Standard Error 1.15	90.8 percent predicted FEV1 Standard Error 1.16

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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%.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-5: Omalizumab vs. Placebo	78.6 percent FEV1/FVC ratio Standard Error 0.44	78.4 percent FEV1/FVC ratio Standard Error 0.78

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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%.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=121 Participants 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.	Treatment Steps 2-5: Placebo n=130 Participants 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.
Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-4: Omalizumab vs. ICS	79.1 percent FEV1/FVC ratio Standard Error 0.64	77.9 percent FEV1/FVC ratio Standard Error 0.65

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available ACT scores

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=95 Participants 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.	Treatment Steps 2-5: Placebo n=22 Participants 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.
Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-5: Omalizumab vs. Placebo	22.9 ACT Score Standard Error 0.19	21.8 ACT Score Standard Error 0.35

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available ACT Scores

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=39 Participants 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.	Treatment Steps 2-5: Placebo n=29 Participants 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.
Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-4: Omalizumab vs. ICS	23.0 ACT Score Standard Error 0.26	22.9 ACT Score Standard Error 0.32

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available C-ACT Scores

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

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=190 Participants 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.	Treatment Steps 2-5: Placebo n=67 Participants 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.
Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-5: Omalizumab vs. Placebo	23.2 C-ACT Score Standard Error 0.19	22.5 C-ACT Score Standard Error 0.31

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available C-ACT Scores

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=82 Participants 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.	Treatment Steps 2-5: Placebo n=101 Participants 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.
Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-4: Omalizumab vs. ICS	23.7 C-ACT Score Standard Error 0.29	23.1 C-ACT Score Standard Error 0.26

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available data

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=136 Participants 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.	Treatment Steps 2-5: Placebo n=41 Participants 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.
Work Disruptions Due to Child's Asthma, Treatment Steps 2-5: Omalizumab vs. Placebo	0.003 Ratio Standard Error 0.001	0.004 Ratio Standard Error 0.003

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat with available data

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

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=59 Participants 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.	Treatment Steps 2-5: Placebo n=75 Participants 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.
Work Disruptions Due to Child's Asthma, Treatment Steps 2-4: Omalizumab vs. ICS	0.003 Ratio Standard Error 0.001	0.003 Ratio Standard Error 0.001

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
School Absences (Percent), Treatment Steps 2-5:Omalizumab vs. Placebo	1.2 Ratio Standard Error 0.20	1.6 Ratio Standard Error 0.47

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=121 Participants 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.	Treatment Steps 2-5: Placebo n=130 Participants 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.
School Absences (Percent), Treatment Steps 2-4: Omalizumab vs. ICS	0.9 Ratio Standard Error 0.25	2.0 Ratio Standard Error 0.63

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=259 Participants 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.	Treatment Steps 2-5: Placebo n=89 Participants 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.
Percent Adherence to Asthma Medication, Treatment Steps 2-5: Omalizumab vs. Placebo	88.6 percent adherence Standard Error 0.77	88.8 percent adherence Standard Error 1.28

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Intent-to-treat

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.

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=82 Participants 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.	Treatment Steps 2-5: Placebo n=101 Participants 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.
Percent Adherence to Asthma Medication, Treatment Steps 2-4: Omalizumab vs. ICS	88.4 percent adherence Standard Error 1.12	88.6 percent adherence Standard Error 1.08

SECONDARY outcome

Timeframe: 90 Day outcome period

Population: Prespecified Outcome Measure: analysis limited to the Omalizumab and Placebo Groups. Analysis: intent-to-treat (with available data).

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).

Outcome measures

Measure	Treatment Steps 2-5: Omalizumab n=179 Participants 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.	Treatment Steps 2-5: Placebo n=61 Participants 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.
Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo Exposure to cockroach. No exacerbations.	37 Participants	18 Participants
Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo Exposure to cockroach. Exacerbations	7 Participants	2 Participants
Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo No exposure to cockroach. No exacerbations.	119 Participants	28 Participants
Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo No exposure to cockroach. Exacerbations	16 Participants	13 Participants

Adverse Events

Omalizumab

Serious events: 0 serious events

Other events: 41 other events

Deaths: 0 deaths

Inhaled Corticosteroid Boost Therapy (ICS)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Omalizumab n=259 participants at risk 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.	Inhaled Corticosteroid Boost Therapy (ICS) n=130 participants at risk 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.	Placebo n=89 participants at risk Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.
Immune system disorders Anaphylactic reaction	0.00% 0/259 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	0.77% 1/130 • Number of events 1 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	0.00% 0/89 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).
Nervous system disorders VIIth nerve paralysis	0.00% 0/259 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	0.00% 0/130 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	1.1% 1/89 • Number of events 1 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).

Other adverse events

Measure	Omalizumab n=259 participants at risk 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.	Inhaled Corticosteroid Boost Therapy (ICS) n=130 participants at risk 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.	Placebo n=89 participants at risk Participants in the placebo group received placebo injection and placebo inhaler. All participants received standardized specialist asthma care.
Infections and infestations Nasopharyngitis	3.9% 10/259 • Number of events 13 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	6.2% 8/130 • Number of events 9 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	3.4% 3/89 • Number of events 3 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).
Nervous system disorders Headache	6.6% 17/259 • Number of events 18 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	3.1% 4/130 • Number of events 5 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	6.7% 6/89 • Number of events 7 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).
Skin and subcutaneous tissue disorders Rash	6.2% 16/259 • Number of events 16 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	3.8% 5/130 • Number of events 5 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).	4.5% 4/89 • Number of events 4 • Treatment initiation visit to end of study. Adverse events reported for intent-to-treat population from the period spanning the initial treatment visit to end of study (up to 90 days).

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place