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

Sponsor:	Genentech
Information provided by (Responsible Party):	Genentech
ClinicalTrials.gov Identifier:	NCT00314574

Purpose

This is a multicenter, randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of subcutaneously administered Xolair as add-on therapy for the treatment of subjects aged 12-75 years old diagnosed with moderate to severe asthma who are inadequately controlled with high-dose inhaled corticosteroids (ICS)+ long-acting beta-agonists (LABA) with or without additional controller therapy.

Condition	Intervention	Phase
Asthma	Drug: omalizumab (Xolair) Drug: placebo Drug: corticosteroids Drug: long-acting beta-agonists	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Xolair in Subjects With Moderate to Severe Persistent Asthma Who Are Inadequately Controlled With High-Dose Inhaled Corticosteroids and Long-Acting Beta-Agonists

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Fluticasone propionate Fluticasone Omalizumab Corticosteroids

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Rate of Asthma Exacerbations Over the 48 Week Treatment Period [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change From Baseline in Total Asthma Symptom Scores [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
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.
Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
Change from baseline to week 48 in mean puffs per day of albuterol. Puffs per day was achieved by week 48 minus baseline.
Change From Baseline in Overall Asthma-related Quality of Life [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
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.
Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
This outcome is represented in the adverse event section of the database.

Enrollment:	850
Study Start Date:	December 2005
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Xolair The subcutaneous dose of Xolair administered in this study was either a 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.	Drug: omalizumab (Xolair) Omalizumab (Xolair) was administered by subcutaneous (SC) injection every 2 or 4 weeks. Xolair was supplied as a sterile, white, preservative-free, lyophilized powder in single-use vials that were reconstituted with Sterile Water for Injection (SWFI), USP. Other Name: Xolair Drug: corticosteroids Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day. Drug: long-acting beta-agonists 50 µg salmeterol twice daily or 12 µg formoterol twice daily.
Placebo Comparator: placebo The subcutaneous dose of placebo administered in this study was either a 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.	Drug: placebo Placebo was administered by subcutaneous (SC) injection every 2 or 4 weeks. Placebo contained the same ingredients as the lyophilized formulation of Xolair,excluding omalizumab. Drug: corticosteroids Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day. Drug: long-acting beta-agonists 50 µg salmeterol twice daily or 12 µg formoterol twice daily.

Arms

Assigned Interventions

Experimental: Xolair

The subcutaneous dose of Xolair administered in this study was either a 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.

Drug: omalizumab (Xolair)

Omalizumab (Xolair) was administered by subcutaneous (SC) injection every 2 or 4 weeks. Xolair was supplied as a sterile, white, preservative-free, lyophilized powder in single-use vials that were reconstituted with Sterile Water for Injection (SWFI), USP.

Other Name: Xolair

Drug: corticosteroids

Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.

Drug: long-acting beta-agonists

50 µg salmeterol twice daily or 12 µg formoterol twice daily.

Placebo Comparator: placebo

The subcutaneous dose of placebo administered in this study was either a 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.

Drug: placebo

Placebo was administered by subcutaneous (SC) injection every 2 or 4 weeks. Placebo contained the same ingredients as the lyophilized formulation of Xolair,excluding omalizumab.

Drug: corticosteroids

Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.

Drug: long-acting beta-agonists

50 µg salmeterol twice daily or 12 µg formoterol twice daily.

Eligibility

Ages Eligible for Study:	12 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed Informed Consent Form and an informed assent, if applicable
Be between the ages of 12 to 75 years
Have had a history of moderate to severe asthma for at least one year prior to screening
Have had treatment with a stable regimen of of salmeterol 50 µg twice a day (BID) or formoterol 12 µg BID for at least 8 weeks prior to screening
Have had treatment with a stable regimen of high-dose inhaled corticosteroids (ICS) for at least 8 weeks prior to screening
Have inadequately controlled asthma
Have had at least one asthma exacerbation requiring systemic corticosteroid rescue in the 12 months prior to the screening visit while receiving treatment with high-dose ICS
Have less than 10 pack-years smoking history
Have a positive skin test for or a positive, in vitro response to one relevant perennial aeroallergen documented within the 12 months prior to screening
If a subject has not had a positive skin test or in vitro reactivity in the 12 months prior to screening, the subject must demonstrate a positive response to at least one relevant perennial aeroallergen in a skin or in vitro test prior to randomization
Female subjects of childbearing potential must use an effective method of contraception from screening through their duration of participation in the study
For the collection of additional blood samples for future research (optional), provide signed consent and an informed assent, if applicable.

Exclusion Criteria:

Have had an asthma exacerbation requiring intubation within 12 months prior to screening
Have active lung disease other than asthma
Have had an asthma exacerbation requiring treatment with the addition of systemic (oral or intravenous) corticosteroids or an increase in systemic corticosteroids within 30 days prior to screening
Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc.
Have significant medical illness other than asthma
Have taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics, within 3 months prior to screening
Have taken other investigational drugs within 30 days prior to screening
Have been treated with Xolair within the 12 months prior to screening
Have a history of drug or alcohol abuse that, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study
Have elevated serum IgE levels for reasons other than allergy
Are pregnant or lactating

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00314574

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Karin Rosen, M.D., Ph.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00314574 History of Changes
Other Study ID Numbers:	Q3662g
Study First Received:	April 12, 2006
Results First Received:	March 31, 2011
Last Updated:	February 8, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Persistent Asthma
EXTRA
Xolair
Difficult Breathing

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Omalizumab

Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 09, 2012