Omalizumab in Non-atopic Asthma

2014-08-27 03:14:05 | BioPortfolio


Hypothesis- Omalizumab(humanized monoclonal anti-IgE antibody)improves disease control and reduces bronchial mucosal inflammation in non-atopic asthma.

In order to test the above hypothesis, the investigators propose a placebo controlled, double blind, parallel group study to obtain proof of principle that omalizumab exerts beneficial effects on disease control in non-atopic severe adult asthmatics aged 18-60 years . Forty patients will be randomized in a 1:1 ratio to receive omalizumab or matching placebo. Following 12 weeks of treatment with omalizumab/placebo, and as this treatment is continued for a further 8 weeks, anti-asthma treatment will be reduced. Dosages will be administered at 4 or 2 weekly intervals over a 16 week period (5 or 10 doses in total), which corresponds with the time stated as necessary to judge efficacy of therapy according to omalizumab's licensed indications in atopic asthma. Efficacy will be judged by clinical monitoring and by bronchial biopsy to assess effects on bronchial inflammation and local IgE production.


The primary aim of the study is to obtain proof of principle that omalizumab therapy maintains lung function, symptom control and quality of life in a group of non-atopic, moderate/severe asthmatics whose regular anti-asthma therapy is uniformised and reduced for an 8 week period following omalizumab/placebo therapy while the latter therapy is continued.

A secondary aim is to see whether omalizumab, as compared with placebo therapy reduces bronchial inflammation and local IgE production in the bronchial mucosa of this same group of asthmatics.

Clinical outcome measures

The omalizumab and placebo treated groups will be compared for changes in the following clinical outcomes (for repeated measurements such as daily peak flow and symptoms the mean values of the first and last 10 days of the relevant study period will be compared).

1. prior to reduction of existing anti-asthma therapy (first 12 weeks of study):

- Pre-bronchodilator FEV1 (primary outcome measure)

- Morning and evening peak expiratory flow

- Exhaled nitric oxide

- Day and night time symptom scores

- Total dosages of rescue beta2-agonist

- Total symptom free days

- Validated asthma Quality of Life scores

2. during anti-asthma therapy reduction phase (subsequent 8 weeks of study):

- The primary outcome measure will be disease exacerbation, defined as a need for rescue oral corticosteroid medication for worsening of symptoms and/or deterioration in lung function, as agreed between the patient and the study physician

- Secondary outcome measures will include all those measurements listed in section (a) above, unless they cannot be measured because of disease exacerbation (the primary outcome measure)

Laboratory outcome measures

These will arise from immunological, immunohistochemical and molecular analysis of peripheral blood and bronchial biopsies taken from all patients at the beginning and end of the first 12 weeks of the study prior to reduction of anti-asthma therapy and will comprise of changes in:

- Lay down of collagen types I, III, IV and V and tenascin

- Vascular structures and angiogenic stimuli (collagen type IV, CD31 and human VEGF (29,30)

- Inflammatory cells (eosinophils, T cells, B cells, plasma cells, macrophages, neutrophils, mast cells)

- Goblet cells will be stained using monoclonal anti-Muc-5AC antibody

- Immunoglobulin E and its high- and low-affinity receptors will be stained using specific monoclonal antibodies as in our previous studies. B cells (CD20+) and plasma cells (CD138+) will be examined for expression of free kappa and lambda IgE light chains using double, sequential IHC.

Staining analysis: Entire areas of stained biopsy sections will be subjected to image analysis using a Zeiss Vision KS300 system allowing objective, unbiased digital image analysis using a powerful macro language .

Cytokine and chemokine concentrations in endobronchial tissue homogenates: These will be measured in homogenates of 2 biopsies by electrochemiluminescence using the SECTOR Imager 6000 and assay kits produced by Meso Scale Discovery. The MS6000 Human TH1/TH2 10-Plex Base Kit will be used to measure IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, TNF-alpha. The MS6000 Human Chemokine 9-Plex Base Kit will be used to measure Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1beta, TARC.

IgE synthesis: Two biopsies from each patient will be snap frozen in RNA later for subsequent analysis of expression of switch circle transcripts and IgE mature and germline mRNA as in our previous recent publication and cloning of C-epsilon H-chain genes to look for evidence of clonal expansion of B cells caused by B cell superantigens. Two biopsies will be

\homogenised for extraction of B cells for cloning and analysis of IgE production by antigen microarray.

Serum: Stored serum samples taken at the time of bronchoscopy will be analysed for complete antigen-specific IgE repertoire using microarray, and anti-Fc-epsilon-RI activity using an in vitro basophil degranulation assay.

Study Design

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


Bronchial Asthma


Omalizumab, Placebo


Guy's Hospital, London, UK
United Kingdom


Not yet recruiting


King's College London

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:14:05-0400

Clinical Trials [1640 Associated Clinical Trials listed on BioPortfolio]

Study of Omalizumab in Moderate to Severe Bronchial Asthma

This study will evaluate the safety and efficacy of omalizumab up to 16 weeks in adult patients with moderate to severe bronchial asthma.

Long-Term Study of IGE025 in Moderate to Severe Bronchial Asthma.

This study will evaluate the safety and efficacy of omalizumab up to 48 weeks in adult patients with moderate to severe bronchial asthma. THIS STUDY IS NOT ENROLLING PATIENTS IN THE UNITE...

Efficacy and Safety of Omalizumab in Patients With Severe Persistent Asthma

The purpose of this study is to determine the effect of omalizumab, compared to placebo, on clinically significant asthma exacerbation rates in adolescents and adults with asthma.

Effects of Omalizumab Compared to Non-Omalizumab Treatment in Asthma Patients

The purpose of this study is effects of Omalizumab compared to non-Omalizumab treatment in the propensity-matched group on asthma exacerbation in asthma patients in Korea: a retrospective ...

A Study of Omalizumab in the Prevention of Allergen Induced Airway Obstruction in Adults With Mild Allergic Asthma

This was a multicenter, randomized, double-blind, parallel-group, three-arm, placebo-controlled study designed to demonstrate the efficacy of two different formulations of omalizumab compa...

PubMed Articles [2079 Associated PubMed Articles listed on BioPortfolio]

A clinical follow-up of omalizumab in routine treatment of allergic asthma monitored by CD-sens.

Omalizumab has been available for treatment of allergic asthma for more than a decade and thus, its efficacy in routine treatment was of interest to evaluate. Basophil allergen threshold sensitivity (...

Efficacy and effectiveness of omalizumab in the treatment of childhood asthma.

Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E, a mediator involved in the clinical manifestations of allergic asthma. Evidence for its efficacy and safety in ...

Hopkins syndrome following the first episode of bronchial asthma associated with enterovirus D68: a case report.

Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of...

Omalizumab lowers asthma exacerbations, oral corticosteroid intake and blood eosinophils: Results of a 5-YEAR single-centre observational study.

Omalizumab is a humanized monoclonal antibody which binds to human immunoglobulins E (IgE), thus preventing their interactions with both high affinity and low affinity IgE receptors. Therefore, omaliz...

Isolated aggregates of lymphoid cells in the inner bronchial wall in asthma patients.

Here, we report findings in volunteers with bronchial asthma. Biopsies were obtained from the inner bronchial wall before and a short time again after segmental allergen provocation. In most of the ba...

Medical and Biotech [MESH] Definitions

Thermal destruction of the excess bronchial SMOOTH MUSCLE tissue with heat delivered through a catheter assembly attached to a BRONCHOSCOPE. It is often used to control BRONCHIAL HYPERREACTIVITY in severe ASTHMA for better AIRWAY MANAGEMENT.

An anti-IgE, recombinant, humanized monoclonal antibody which specifically binds to the C epsilon3 domain of IMMUNOGLOBULIN E, the site of high-affinity IgE receptor binding. It inhibits the binding of IgE to MAST CELLS and BASOPHILS to reduce the severity of the allergic response and is used in the management of persistent allergic ASTHMA.

A beta-2 adrenergic agonist used in the treatment of ASTHMA and BRONCHIAL SPASM.

A histamine analog and H1 receptor agonist that serves as a vasodilator. It is used in MENIERE DISEASE and in vascular headaches but may exacerbate bronchial asthma and peptic ulcers.

A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.

More From BioPortfolio on "Omalizumab in Non-atopic Asthma"

Quick Search


Relevant Topics

Asthma is caused by inflammation of small tubes, called bronchi, which carry air in and out of the lungs. If you have asthma, the bronchi will be inflamed and more sensitive than normal.  When you come into contact with something that irritates your...

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

The term allergy is used to describe a response, within the body, to a substance, which is not necessarily harmful in itself, but results in an immune response and a reaction that causes symptoms and disease in a predisposed person, which in turn can cau...

Searches Linking to this Trial