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

NCT00670930 | Completed Phase 4 Results

• 2 other identifiers: CIGE025A24322007-004653-29
• Study Type: interventional
• Target: 36
• Locations: 7 countries
• Sites: 16

Brief 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.

Conditions

Allergic Asthma

Keywords

Asthma, adults, anti-immunoglobulin E ( IgE), omalizumab, airway inflammation, airway remodeling, allergy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline in Sub-epithelial Cell Count of Mast Cells Following 78 Weeks Treatment, as Assessed Biopsy Samples

  Baseline, at end of week 78

• Change From Baseline in Sub-epithelial CD4+ T-lymphocytes Following 78 Weeks Treatment, as Assessed Biopsy Samples

  Baseline, at end of week 78

• Change From Baseline in Thickness of the Lamina Reticularis Following 78 Weeks Treatment, as Assessed Biopsy Samples

  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

Study Arms (2)

omalizumab

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

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

Interventions

omalizumab at a dose of 0.016mg/kg/IU/mL DRUG

omalizumab

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Genentech, Inc.: collaborator

Study Sites (16)

Novartis Investigative Site

Denver, Colorado, 80206, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19140, United States

Location

Novartis Investigative Site

Galveston, Texas, 77555-1083, United States

Location

Novartis Investigative Site

Calgary, Alberta, T2N 4N1, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2X 2P4, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1V 4G5, Canada

Location

Novartis Investigative Site

Montpellier, 34059, France

Location

Novartis Investigative Site

Mainz, Germany, D-55101, Germany

Location

Novartis Investigative Site

Leiden 2333 ZA, Netherlands, 2333, Netherlands

Location

Novartis Investigative Site

Lund, SE-221 85, Sweden

Location

Novartis Investigative Site

Glasgow - Scotland, G12 OYN, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 8LR, United Kingdom

Location

Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• patient recruitment website

MeSH Terms

Conditions

Asthma; Epilepsy, Idiopathic Generalized; Airway Remodeling; Hypersensitivity

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2008
• First Posted: May 2, 2008
• Study Start: April 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 18, 2013
• Results First Posted: January 18, 2013

Record last verified: 2012-11

Locations

FR (1); NL (1); GB (3); SE (1); DE (1); US (6); CA (3)