A Study Evaluating the Persistency of Response With or Without Xolair (Omalizumab) After Long-term Therapy

Phase 4

Completed

• Conditions: Allergic Asthma
• Interventions: Drug: Placebo; Drug: Omalizumab; Drug: Asthma therapies

• Registration Number: NCT01125748
• Lead Sponsor: Genentech, Inc.

Brief Summary

This was a randomized, double-blind, placebo-controlled, 2-arm, 1-year study of participants who completed the EXCELS study (NCT00252135) and had received long-term treatment with Xolair. In addition, participants who did not participate in the EXCELS study but received long-term (\~5 years) treatment with Xolair were allowed to enter the study.

Detailed Description

The treatment designation for participants who reached the primary efficacy endpoint (1 protocol-defined severe asthma exacerbation) was unblinded to allow appropriate clinical intervention. Participants who had their treatment designation unblinded remained in the study for ongoing evaluation of safety and were allowed to continue on study drug known to be Xolair (or to start study drug known to be Xolair if they were in the placebo group).

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-05-14
• Study First Submitted QC: 2010-05-17
• Study First Posted: 2010-05-18
• Primary Completion: 2013-08
• Study Completion: 2013-08
• Status Verified: 2014-10
• Results First Submitted: 2014-10-08
• Results First Submitted QC: 2014-10-08
• Last Update Submitted: 2014-10-08
• Results First Posted: 2014-10-15
• Last Update Posted: 2014-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 176

Inclusion Criteria

• Signed Informed Consent Form (ICF). In the case of a minor, consent must be given by the child's parent or legally authorized representative.
• Participants who have completed the EXCELS study prior to this study must have met all inclusion criteria for enrollment in the EXCELS study.
• History of positive skin test or in vitro reactivity to an aeroallergen.
• Continuous Xolair (omalizumab) exposure from the beginning of the EXCELS study to randomization into this study (if the participant participated in the EXCELS study), or within the previous 5 years prior to randomization into this study (if the participant did not participate in the EXCELS study). For the purposes of this study, continuous Xolair exposure is defined as having missed no more than 25% of scheduled Xolair doses. In addition, a maximum of 2 doses can be missed within the last 6 months before being randomized into this study. For participants who did not participate in the EXCELS study, missed-dose rates will be based on their injection records.
• Patients who participated in the EXCELS study must have completed the EXCELS study and not discontinued Xolair since the completion of the EXCELS study.
• Diagnosis of moderate to severe persistent allergic asthma while on Xolair as defined per physician's assessment.
• Stable dosing of current asthma therapies, in addition to Xolair, over 2 months prior to enrollment.
• Serum IgE level ≥ 30 to ≤ 700 IU/mL before initiation of Xolair treatment (prior to the EXCELS study enrollment or earlier).
• Body weight ≥ 30 to ≤ 150 kg.
• Treatment with Xolair consistent with the US package insert (USPI) (based on the dosing table, recommended dose, administration, and dosing interval) prior to enrollment to this study.
• Participants who participated in the EXCELS study must be willing to allow their EXCELS study data to be used in this study as part of baseline demographic values (such as forced expiratory volume in 1 second [FEV1] and Asthma Control Test [ACT]), as documented in the ICF.

Exclusion Criteria

• Participation in other therapy trials or planned participation during the following year from screening.
• Contraindication to Xolair therapy (eg, participants who experienced a severe hypersensitivity reaction to Xolair).
• Acute asthma exacerbation within the 2 months immediately prior to screening that required any of the following: Initiation of systemic corticosteroids, increased dosing of systemic corticosteroids relative to "stable" dose, doubling of inhaled corticosteroid (ICS) dosing, emergency room visit, and hospitalization.
• Any significant, or unstable, systemic disease (eg, infection, hematologic, renal, hepatic, cardiovascular diseases, or gastrointestinal diseases), or a recent hospitalization because of systemic disease within the previous 2 months.
• Diagnosis of active lung disease other than asthma.
• Having more than 10 pack-years smoking history.
• Diagnosis of cystic fibrosis.
• Use of an experimental drug within 30 days prior to study screening.
• Unable or unwilling to comply with study procedures and visits (eg, spirometry, blood draws).
• Have elevated serum IgE levels for reasons other than allergy (eg, parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich syndrome, or bronchopulmonary aspergillosis).
• Pregnancy, lactation, or any planned pregnancy in the following year.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo subcutaneously at the same dosing interval as omalizumab was administered prior to enrollment in this study.
Omalizumab	Asthma therapies	Participants received omalizumab subcutaneously at the same dose and dosing interval as administered prior to enrollment in this study. The dose of omalizumab 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.
Placebo	Asthma therapies	Participants received placebo subcutaneously at the same dosing interval as omalizumab was administered prior to enrollment in this study.
Omalizumab	Omalizumab	Participants received omalizumab subcutaneously at the same dose and dosing interval as administered prior to enrollment in this study. The dose of omalizumab 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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Not Experiencing a Protocol-defined Severe Exacerbation During the Study	Baseline to the end of the study (up to 52 weeks)	A protocol-defined severe exacerbation was a clinically significant worsening of asthma which, in the clinical judgment of the investigator, required at least 1 of the following: (1) Initiation of systemic corticosteroid treatment (tablets, suspension, or injection) or an increase in the level of systemic corticosteroid treatment from a stable maintenance dose for at least 3 days (For patients taking chronic oral corticosteroids, a protocol-defined severe exacerbation was any clinically significant worsening of asthma requiring ≥ 3 days of treatment with at least a 20 mg increase in the average daily dose of oral prednisone or a comparable dose of systemic corticosteroids) or (2) a hospitalization or emergency room visit because of asthma requiring systemic corticosteroids.

Secondary Outcome Measures

Name	Time	Method
Time to the First Protocol-defined Severe Exacerbation	Baseline to the end of the study (up to 52 weeks)	A protocol-defined severe exacerbation was a clinically significant worsening of asthma which, in the clinical judgment of the investigator, required at least 1 of the following: (1) Initiation of systemic corticosteroid treatment (tablets, suspension, or injection) or an increase in the level of systemic corticosteroid treatment from a stable maintenance dose for at least 3 days (For patients taking chronic oral corticosteroids, a protocol-defined severe exacerbation was any clinically significant worsening of asthma requiring ≥ 3 days of treatment with at least a 20 mg increase in the average daily dose of oral prednisone or a comparable dose of systemic corticosteroids) or (2) a hospitalization or emergency room visit because of asthma requiring systemic corticosteroids.