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)

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00670930
First received: April 30, 2008
Last updated: December 12, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Allergic Asthma
Drug: omalizumab at a dose of 0.016mg/kg/IU/mL
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Total Subepithelial Eosinophils at the End of Week 78 (End of Treatment) [ Time Frame: Baseline, at end of week 78 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Sub-epithelial Cell Count of Mast Cells Following 78 Weeks Treatment, as Assessed Biopsy Samples [ Time Frame: Baseline, at end of week 78 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Sub-epithelial CD4+ T-lymphocytes Following 78 Weeks Treatment, as Assessed Biopsy Samples [ Time Frame: Baseline, at end of week 78 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Thickness of the Lamina Reticularis Following 78 Weeks Treatment, as Assessed Biopsy Samples [ Time Frame: Baseline, at end of week 78 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events, Serious Adverse Events and Death as an Assessment of Safety and Tolerability of 78 Weeks Therapy [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: April 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670930

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

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00670930     History of Changes
Other Study ID Numbers: CIGE025A2432, 2007-004653-29
Study First Received: April 30, 2008
Results First Received: November 16, 2012
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Sweden: Medical Products Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:
Asthma, adults, anti-immunoglobulin E ( IgE), omalizumab, airway inflammation, airway remodeling, allergy

Additional relevant MeSH terms:
Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Immunoglobulin E
Immunoglobulins
Omalizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Allergic Agents
Therapeutic Uses
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on August 26, 2014