Trial Outcomes & Findings for Omalizumab in Patients With Moderate to Severe Persistent Allergic Asthma Not Adequately Controlled Despite GINA (2009) Step 4 Therapy (NCT NCT01202903)

NCT ID: NCT01202903

Last Updated: 2015-03-23

Results Overview

A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 616 participants
• Primary outcome timeframe: Baseline, 24 weeks
• Results posted on: 2015-03-23

Participant Flow

Of the 616 patients randomized 7 (2 omalizumab and 5 placebo) did not receive drug and were excluded from the Full Analysis Set (FAS) and Safety Set.

One additional patient did not receive study drug for greater than 60 days and was also removed from the FAS. 4 patients initially randomized to the placebo group received omalizumab at one or more administration and were considered part of the omalizumab group for the Safety Set.

Participant milestones

Measure	Omalizumab Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Overall Study STARTED	308	308
Overall Study Full Analysis Set	306	302
Overall Study Safety Set*	310	299
Overall Study COMPLETED	297	292
Overall Study NOT COMPLETED	11	16

Reasons for withdrawal

Measure	Omalizumab Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Overall Study Administrative Probelms	1	4
Overall Study Protocol Violation	0	1
Overall Study Death	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Lack of Efficacy	1	3
Overall Study Adverse Event	3	3
Overall Study Withdrawal by Subject	4	4

Baseline Characteristics

Omalizumab in Patients With Moderate to Severe Persistent Allergic Asthma Not Adequately Controlled Despite GINA (2009) Step 4 Therapy

Baseline characteristics by cohort

Measure	Omalizumab n=310 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=299 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.	Total n=609 Participants Total of all reporting groups
Age, Continuous	45.8 Years STANDARD_DEVIATION 12.03 • n=5 Participants	47.1 Years STANDARD_DEVIATION 11.64 • n=7 Participants	46.5 Years STANDARD_DEVIATION 11.85 • n=5 Participants
Age, Customized 18-<65 years	290 Participants n=5 Participants	285 Participants n=7 Participants	575 Participants n=5 Participants
Age, Customized 65<=75 years	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Female	171 Participants n=5 Participants	157 Participants n=7 Participants	328 Participants n=5 Participants
Sex: Female, Male Male	139 Participants n=5 Participants	142 Participants n=7 Participants	281 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) Following the 24-week Treatment Period	27.03 L/min Standard Error 20.865	18.18 L/min Standard Error 21.086

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.

Outcome measures

Measure	Omalizumab n=292 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=289 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in Mean Evening PEF (L/Min) Following 24-week Treatment	22.96 L/min Standard Error 20.145	15.53 L/min Standard Error 20.350

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

Spirometry was used at defined time points throughout the study to assess the clinical status of patients and to capture the following variables: forced expiratory volume in one second (FEV1), FEV1 percent predicted, forced vital capacity (FVC) and the FEV1/FVC ratio. During the Screening assessment, spirometry was performed pre- and post-bronchodilator administration to assess reversibility. During the treatment period (including prerandomization assessments on Day 1), spirometry was performed after withholding bronchodilators. The results of spirometry were required to meet the ATS/ERS criteria for acceptability and repeatability. Acceptability criteria were applied before repeatability was determined. LS Mean of change from baseline in % predicted FEV1 is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline % predicted FEV1 as covariates.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in % Predicted FEV1 Following 24-week Treatment	19.113 L/min Standard Error 5.6130	14.989 L/min Standard Error 5.6645

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

The standardized version of the Asthma Quality of Life Questionnaire (AQLQs)), was used to assess the patients' asthma-related quality of life. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in AQLQ Score Following 24-week Treatment Overall Score (n=182,178)	0.51 Units on a scale Standard Error 0.155	0.10 Units on a scale Standard Error 0.155
Change From Baseline in AQLQ Score Following 24-week Treatment Symptom Score (n=208,206)	0.47 Units on a scale Standard Error 0.143	0.18 Units on a scale Standard Error 0.142
Change From Baseline in AQLQ Score Following 24-week Treatment Activity Score (n=203,198)	0.46 Units on a scale Standard Error 0.133	0.17 Units on a scale Standard Error 0.131
Change From Baseline in AQLQ Score Following 24-week Treatment Emotions Score (n=217,213)	0.64 Units on a scale Standard Error 0.184	0.36 Units on a scale Standard Error 0.181
Change From Baseline in AQLQ Score Following 24-week Treatment Environmental Score (n=201,203)	0.54 Units on a scale Standard Error 0.199	0.17 Units on a scale Standard Error 0.199

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

The standardized version of the Asthma Quality of Life Questionnaire (AQLQs)), was used to assess the patients' asthma-related quality of life. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Percentage of Patients Achieving at Least a 0.5, 1.0 or 1.5 Point Improvement From Baseline in AQLQ Overall Score Following 24-week Treatment >=0.5 to <1.0	12.1 Percent	10.6 Percent
Percentage of Patients Achieving at Least a 0.5, 1.0 or 1.5 Point Improvement From Baseline in AQLQ Overall Score Following 24-week Treatment >=1.0 to <1.5	9.2 Percent	6.6 Percent
Percentage of Patients Achieving at Least a 0.5, 1.0 or 1.5 Point Improvement From Baseline in AQLQ Overall Score Following 24-week Treatment >=1.5	13.4 Percent	6.0 Percent
Percentage of Patients Achieving at Least a 0.5, 1.0 or 1.5 Point Improvement From Baseline in AQLQ Overall Score Following 24-week Treatment Missing	40.5 Percent	41.1 Percent

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

The Asthma Control Questionnaire (ACQ) is a questionnaire consisting of 7 questions assessing symptoms, airway caliber and rescue β2-agonist use. One value representing overall asthma control on that occasion was calculated. Decrease in scores of 0.5 or higher between ACQ assessments are considered clinically meaningful. The ACQ was completed by the patient at the Investigator's site at Visit 2 (Week 1, pre-dose), Visit 6 (after completion of 16 weeks of treatment) and at the End of Study/Early Termination visit. LS Mean of change from baseline in ACQ score is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, center grouping, smoking status, and baseline ACQ score as covariates. Score 0= totally controlled, 6= extremely poorly controlled

Outcome measures

Measure	Omalizumab n=210 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=211 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in ACQ Score Following 24-week Treatment	-0.51 Units on a scale Standard Error 0.092	-0.34 Units on a scale Standard Error 0.091

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

The Asthma Control Questionnaire (ACQ) is a questionnaire consisting of 7 questions assessing symptoms, airway caliber and rescue β2-agonist use. One value representing overall asthma control on that occasion was calculated. Decrease in scores of 0.5 or higher between ACQ assessments are considered clinically meaningful. The ACQ was completed by the patient at the Investigator's site at Visit 2 (Week 1, pre-dose), Visit 6 (after completion of 16 weeks of treatment) and at the End of Study/Early Termination visit. Only patients with no more than 1 item missing are included, and the missing item was imputed by interpolation

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24 <= -0.75 ACQ improvement	23.5 Percent	15.2 Percent
Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24 > -0.75 ACQ improvement	45.1 Percent	54.6 Percent
Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24 Missing	31.4 Percent	30.1 Percent
Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24 <= -0.5 ACQ improvement	34 Percent	24.8 Percent
Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24 > -0.5 ACQ improvement	34.6 Percent	45.0 Percent

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

Total asthma symptom score was derived for each day as the total of the morning (scale 0-1), daytime (scale 0-4) and nocturnal (scale 0-4) scores with a max score of 9. The mean score across the 28 days prior to the week 24 assessment visit was used to calculate a change from baseline. Analysis of total asthma symptom score was performed using ANCOVA model and Van-Elteren test. LS Mean of change from baseline in mean asthma symptom score is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, smoking status, center grouping, and baseline mean asthma symptom scores as covariates. Decrease of score on change from baseline means improvement of asthma symptom control.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in Asthma Symptom Scores Following 24-week Treatment Total symptom score (n=287,282)	-1.65 Units on a scale Standard Error 0.462	-1.44 Units on a scale Standard Error 0.466
Change From Baseline in Asthma Symptom Scores Following 24-week Treatment Night-time symptom (n=292,288)	-0.67 Units on a scale Standard Error 0.203	-0.55 Units on a scale Standard Error 0.205
Change From Baseline in Asthma Symptom Scores Following 24-week Treatment Morning symptom (n=292,288)	-0.21 Units on a scale Standard Error 0.089	-0.20 Units on a scale Standard Error 0.090
Change From Baseline in Asthma Symptom Scores Following 24-week Treatment Daytime symptom (n=292,288)	-0.79 Units on a scale Standard Error 0.246	-0.72 Units on a scale Standard Error 0.248

SECONDARY outcome

Timeframe: 16 and 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

The global evaluation of treatment effectiveness (GETE) is an assessment of asthma symptom control and overall response to asthma treatment. The evaluation was performed by both investigator and patient, each using the same 5 point scale. The GETE scale ranges were as follows: excellent, good, moderate, poor and worsening. A good or excellent response on the 5 point scale indicated that a patient had responded to treatment. 1=excellent 2=good 3=moderate 4=poor 5= worsening. Responder is defined as the patient who achieved an excellent or good response. Non-responder isdefined as the patient who achieved a moderate or poor or worsening response.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Investigator responder	71.9 Percent	52.3 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Investigator non-responder	25.5 Percent	44.4 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Investigator missing	2.6 Percent	3.3 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Patient responder	70.6 Percent	59.6 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Patient non-responder	26.8 Percent	37.1 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 16 Patient Missing	2.6 Percent	3.3 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Investigator responder	70.3 Percent	50.7 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Investigator non-responder	26.5 Percent	45.7 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Investigator missing	3.3 Percent	3.6 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Patient responder	71.9 Percent	61.6 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Patient non-responder	24.8 Percent	34.8 Percent
Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24 Week 24 Patient Missing	3.3 Percent	3.6 Percent

SECONDARY outcome

Timeframe: 24 weeks

Population: The FAS consisted of all randomized patients who received at least one dose of study drug. 7 randomized patients did not receive study drug and were excluded along with 1 other patient who did not receive study drug for more than 60 days

Analysis of rescue medication use followed a similar method to that employed for total asthma symptom score. The mean number of puffs across the 28 days prior to the Week 24 assessment visit was used to calculate a change from baseline. LS Mean of change from baseline in mean number of puffs of asthma rescue medication is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, smoking status, center grouping, and baseline mean number of puffs of asthma rescue medication as covariates.

Outcome measures

Measure	Omalizumab n=306 Participants Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=302 Participants The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Change From Baseline in Number of Puffs of Asthma Rescue Medication Following 24-week Treatment Daily number of puffs (n=296,291)	-1.14 Number of puffs Standard Error 0.566	-0.85 Number of puffs Standard Error 0.572
Change From Baseline in Number of Puffs of Asthma Rescue Medication Following 24-week Treatment Daytime number of puffs (n=292-289)	-0.53 Number of puffs Standard Error 0.301	-0.38 Number of puffs Standard Error 0.304
Change From Baseline in Number of Puffs of Asthma Rescue Medication Following 24-week Treatment Nighttime number of puffs (n=292-289)	-0.56 Number of puffs Standard Error 0.276	-0.42 Number of puffs Standard Error 0.279

Adverse Events

Omalizumab

Serious events: 8 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo

Serious events: 11 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Measure	Omalizumab n=310 participants at risk Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=299 participants at risk The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
Gastrointestinal disorders Haemorrhoids	0.32% 1/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Pneumonia	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.67% 2/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Pulmonary tuberculosis	0.32% 1/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Upper respiratory tract infection	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.33% 1/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.33% 1/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Injury, poisoning and procedural complications Patella fracture	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.33% 1/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.32% 1/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.32% 1/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.33% 1/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Reproductive system and breast disorders Ovarian cyst	0.32% 1/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Asthma	0.97% 3/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	2.3% 7/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.33% 1/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.

Other adverse events

Measure	Omalizumab n=310 participants at risk Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 mL vial that was designed to deliver 150 mg of omalizumab for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection. The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.	Placebo n=299 participants at risk The placebo was the same mixture of inactive excipients, in quality and quantity, as those used for the drug product. The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.
General disorders Pyrexia	1.3% 4/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.67% 2/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Influenza	0.97% 3/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	1.7% 5/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Nasopharyngitis	6.5% 20/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	8.7% 26/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Infections and infestations Upper respiratory tract infection	12.9% 40/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	12.7% 38/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Nervous system disorders Dizziness	1.6% 5/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.67% 2/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Nervous system disorders Headache	0.97% 3/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	1.3% 4/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Asthma	10.0% 31/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	12.4% 37/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Cough	1.3% 4/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.67% 2/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 5/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	0.00% 0/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.3% 4/310 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.	1.7% 5/299 The Safety Set consisted of all patients who received at least one dose of study medication whether or not being randomized. Patients were analyzed according to the treatment they actually received. If patients switched between placebo and omalizumab during the study, they were analyzed according to omalizumab.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER