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

Allergic Asthma Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670930
• Other study ID #: CIGE025A2432
• Secondary ID: 2007-004653-29
• Status: Completed
• Phase: Phase 4
• First received: April 30, 2008
• Last updated: December 12, 2012
• Start date: April 2008
• Est. completion date: November 2011

Study information

• Verified date: November 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSweden: Medical Products AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Allergic Asthma
• Asthma

Intervention

Drug:
• omalizumab at a dose of 0.016mg/kg/IU/mL

• Placebo

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
France	Novartis Investigative Site	Montpellier
Germany	Novartis Investigative Site	Mainz
Netherlands	Novartis Investigative Site	Leiden 2333 ZA
Sweden	Novartis Investigative Site	Lund
United Kingdom	Novartis Investigative Site	Glasgow - Scotland
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Southampton
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Galveston	Texas
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Participants With Adverse Events, Serious Adverse Events and Death as an Assessment of Safety and Tolerability of 78 Weeks Therapy		78 weeks	Yes