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:
Novartis Pharmaceuticals
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
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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
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 May 21, 2013