Trial Outcomes & Findings for A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA) (NCT NCT00314574)

Last Updated: 2012-02-09

Results Overview

A protocol-defined asthma exacerbation was defined as worsening of asthma symptoms requiring treatment with systemic corticosteroids for 3 or more days; for patients receiving long-term oral corticosteroids, an exacerbation was a 20 mg or more increase in average daily dose of oral prednisone (or a similar dose of another systemic corticosteroid). The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 48 week treatment period in each treatment group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

850 participants

Primary outcome timeframe

48 weeks

Results posted on

2012-02-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Overall Study STARTED	423	427
Overall Study Received at Least One Dose of Study Drug	421	427
Overall Study Safety Population	420	428
Overall Study COMPLETED	329	344
Overall Study NOT COMPLETED	94	83

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Overall Study Death	3	0
Overall Study Adverse Event	11	16
Overall Study Lost to Follow-up	19	25
Overall Study Withdrawal by Subject	33	22
Overall Study Physician Decision	22	15
Overall Study Pregnancy	6	4
Overall Study Data unknown at database lock	0	1

Baseline Characteristics

A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=421 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=427 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Total n=848 Participants Total of all reporting groups
Age, Categorical <=18 years	16 Participants n=99 Participants	23 Participants n=107 Participants	39 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	376 Participants n=99 Participants	379 Participants n=107 Participants	755 Participants n=206 Participants
Age, Categorical >=65 years	29 Participants n=99 Participants	25 Participants n=107 Participants	54 Participants n=206 Participants
Age Continuous	45.3 years STANDARD_DEVIATION 13.9 • n=99 Participants	43.7 years STANDARD_DEVIATION 14.3 • n=107 Participants	44.5 years STANDARD_DEVIATION 14.1 • n=206 Participants
Sex: Female, Male Female	295 Participants n=99 Participants	262 Participants n=107 Participants	557 Participants n=206 Participants
Sex: Female, Male Male	126 Participants n=99 Participants	165 Participants n=107 Participants	291 Participants n=206 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Modified Intent-to-Treat population included all randomized patients who received at least 1 dose of study drug (Xolair or placebo).

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=427 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Rate of Asthma Exacerbations Over the 48 Week Treatment Period	0.88 exacerbation/patient-week Interval 0.6139 to 0.9212	0.66 exacerbation/patient-week Interval 0.6139 to 0.9212

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: Modified Intent-to-Treat population included all randomized patients who received at least 1 dose of study drug. Ten patients were missing baseline values and were excluded from the analyses. The Last Observation Carried Forward was used to impute missing values at week 48 for patients who discontinued the study early.

Change from baseline to week 48 in Total Asthma Symptom Score (TASS), which included a nocturnal asthma score (0 to 4 scale), morning asthma symptoms (yes or no), and a daytime asthma symptom score (0 to 4 scale, total score range 0 to 9, higher TASS scores represent worse symptoms; breathlessness, tightness in chest, wheezing and cough. Score achieved by week 48 minus baseline.

Outcome measures

Outcome measures
Measure	Placebo n=417 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=421 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Change From Baseline in Total Asthma Symptom Scores	-1.36 score on a scale Standard Deviation 1.87 • Interval -0.49 to -0.01	-1.61 score on a scale Standard Deviation 1.85 • Interval -0.49 to -0.01

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: Modified Intent-to-Treat population included all randomized patients who received at least 1 dose of study drug (Xolair or placebo). Five patients were missing baseline values and were excluded from the analyses. The Last Observation Carried Forward was used to impute missing values at week 48 for patients who discontinued the study early.

Change from baseline to week 48 in mean puffs per day of albuterol. Puffs per day was achieved by week 48 minus baseline.

Outcome measures

Outcome measures
Measure	Placebo n=417 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=426 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication	-1.35 puffs per day Standard Deviation 2.69	-1.57 puffs per day Standard Deviation 2.58

SECONDARY outcome

Timeframe: Baseline and Week 48

Change from baseline to week 48 in overall asthma-specific health-related quality of life, as measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ\[S\]) score. The AQLQ(S) consists of 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; the overall score is the mean of these 32 items on a scale of 1 to 7 (1 = severe impairment, 7 = no impairment). Overall outcome achieved by mean visit minus baseline.

Outcome measures

Outcome measures
Measure	Placebo n=418 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=425 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Change From Baseline in Overall Asthma-related Quality of Life	0.96 score on a scale Standard Deviation 1.26 • Interval 0.07 to 0.39	1.16 score on a scale Standard Deviation 1.22 • Interval 0.07 to 0.39

SECONDARY outcome

Timeframe: Week 48

Population: Safety Population: The safety-evaluable population comprised 848 patients (428 Xolair group and 420 placebo group). Patients in the safety-evaluable population were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.

This outcome is represented in the adverse event section of the database.

Outcome measures

Outcome measures
Measure	Placebo n=420 Participants Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=428 Participants Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events	420 participants	428 participants

Adverse Events

Placebo

Serious events: 44 serious events

Other events: 339 other events

Deaths: 0 deaths

Xolair

Serious events: 40 serious events

Other events: 329 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=420 participants at risk Placebo subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.	Xolair n=428 participants at risk Omalizumab (Xolair) subcutaneous dose minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study.
Infections and infestations sinusitis	18.8% 79/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	18.9% 81/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations bronchitis	14.3% 60/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	15.4% 66/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations nasopharyngitis	9.0% 38/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	8.4% 36/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations acute sinusitis	4.5% 19/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	5.4% 23/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations influenza	4.0% 17/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	5.1% 22/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations urinary tract infection	6.0% 25/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	4.7% 20/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Infections and infestations upper respiratory infection	22.1% 93/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	22.4% 96/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Musculoskeletal and connective tissue disorders back pain	5.5% 23/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	3.5% 15/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Nervous system disorders headache	8.1% 34/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	9.6% 41/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.
Respiratory, thoracic and mediastinal disorders cough	6.9% 29/420 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.	5.8% 25/428 • 48 Weeks The safety-evaluable population, used for all safety analyses, included all randomized subjects who received at least one study drug. Subjects were analyzed according to the actual treatment received. One subject was assigned to receive placebo but inadvertently received at least one dose of xolair during the study.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee "The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights."
Publication restrictions are in place

Restriction type: OTHER