Efficacy of Omalizumab in Adults (18-60 Years of Age) With Moderate-Severe, Persistent Allergic Asthma, Despite Receiving Inhaled Corticosteroids and Long Acting Beta-agonists (eXplore)

A Randomized, Multi-center, Double-blind, Placebo-controlled, Parallel-group Trial to Explore the Effects of 78 Weeks Omalizumab Treatment Given as Add on Therapy on Markers of Airway Inflammation and Remodeling in Patients With Moderate to Severe Persistent Allergic Asthma Receiving Inhaled Corticosteroids and Long Acting Beta-agonists

This study aims to investigate the effect of omalizumab on the number of tissue eosinophils and other markers of airway inflammation and remodeling, including thickness of the lamina reticularis, in moderate to severe asthmatics with persistent symptoms and evidence of airway inflammation despite treatment with inhaled corticosteroids and long acting beta-agonists. This study will also investigate the correlation between systemic and pulmonary inflammation, and the correlation between clinical outcomes and changes within the tissue, to assist in the future identification of patients with tissue eosinophilia and their response to treatment, without the need for invasive bronchoscopy.

Study Overview

• Status: Completed
• Conditions: Allergic Asthma
• Intervention / Treatment: Drug: Placebo; Drug: omalizumab at a dose of 0.016mg/kg/IU/mL

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • Novartis Investigative Site
• France
  • Montpellier, France, 34059
    • Novartis Investigative Site
• Germany
  • Mainz, Germany, D-55101
    • Novartis Investigative Site
• Netherlands
  • Leiden 2333 ZA, Netherlands, 2333
    • Novartis Investigative Site
• Sweden
  • Lund, Sweden, SE-221 85
    • Novartis Investigative Site
• United Kingdom
  • Glasgow - Scotland, United Kingdom, G12 OYN
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 8LR
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Novartis Investigative Site
  • Texas
    • Galveston, Texas, United States, 77555-1083
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients 18-75 years of age with moderate to severe persistent allergic asthma receiving a high dose inhaled corticosteroid (≥800µg per day BDP or equivalent) and a regular long acting beta-agonist for at least 3 months prior to screening
• With a body weight between 20 and 150kg and a serum total IgE level of 30 to 700 IU/mL
• With ≥2% eosinophilia in induced sputum at screening
• With post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% predicted
• With a positive skin prick test (diameter of wheal ≥ 3 mm) or RAST test to at least one perennial aero-allergen (eg. dust mite, cat/dog dander, cockroaches), documented within the past 2 years or demonstrated at Visit 1, to which the patient will be exposed on a regular basis (most days) for the duration of the study.

Exclusion Criteria:

• Patients who've had an asthma exacerbation during the 4 weeks prior to randomization
• Current smokers, stopped smoking within the last 12 months or have a smoking history of >10 pack years
• History of severe allergy to food or drugs
• Previous treatment with omalizumab
• Any patient considered to be unsuitable to bronchoscopy, according to the judgment of the investigator

Other protocol-defined inclusion/exclusion criteria applied.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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 (SQ) administration upon reconstitution with 1.4 ml sterile water for injection. The dose administered was individualized for each patient based on the patient's body weight and total serum Immunoglobulin E (IgE) level at Visit 1 and the number of injections and injection volume was determined using protocol-specified dosing tables. Omalizumab 75 to 375 mg was administered SQ every 2 or 4 weeks depending on the dose for the 78 weeks duration of double-blinded treatment.	Drug: omalizumab at a dose of 0.016mg/kg/IU/mL
Placebo Comparator: Placebo; Omalizumab matching placebo was supplied as lyophilized, sterile powder in a single-use, 5 ml vial that was designed to deliver omalizumab matching placebo for subcutaneous (SQ) administration upon reconstitution with 1.4 ml sterile water for injection. The number of injections and injection volume was individualized for each patient based on the patient's body weight and total serum Immunoglobulin E (IgE) level at Visit 1 and was determined using protocol-specified dosing tables. Placebo was administered SQ every 2 or 4 weeks for the 78 weeks duration of double-blinded treatment.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Subepithelial Eosinophils at the End of Week 78 (End of Treatment)	The primary variable of change from baseline in total epithelia eosinophils at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.	Baseline, at end of week 78

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sub-epithelial Cell Count of Mast Cells Following 78 Weeks Treatment, as Assessed Biopsy Samples	The variable of change from baseline in Sub-epithelial cell count of mast cells at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.	Baseline, at end of week 78
Change From Baseline in Sub-epithelial CD4+ T-lymphocytes Following 78 Weeks Treatment, as Assessed Biopsy Samples	The variable of change from baseline in Sub-epithelial CD4+ T-lymphocytes at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.	Baseline, at end of week 78
Change From Baseline in Thickness of the Lamina Reticularis Following 78 Weeks Treatment, as Assessed Biopsy Samples	The variable of change from baseline in thickness of the lamina reticularis at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.	Baseline, at end of week 78
Number of Participants With Adverse Events, Serious Adverse Events and Death as an Assessment of Safety and Tolerability of 78 Weeks Therapy		78 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Genentech, Inc.

Publications and helpful links

Helpful Links

• patient recruitment website

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: April 30, 2008
• First Submitted That Met QC Criteria: May 1, 2008
• First Posted (Estimate): May 2, 2008

Study Record Updates

• Last Update Posted (Estimate): January 18, 2013
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Asthma, adults, anti-immunoglobulin E ( IgE), omalizumab, airway inflammation, airway remodeling, allergy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: CIGE025A2432; 2007-004653-29 (EudraCT Number)