* Primary objective: To determine the effect of 78-weeks therapy with omalizumab compared to placebo on the number of sub-epithelial eosinophils, a marker of airway inflammation, in patients with persistent moderate to severe allergic asthma. *…
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* To evaluate the effect of 78-weeks therapy with omalizumab compared to
placebo on additional markers of airway inflammation, including the number of
interleukin-13+ or -4+ cells, and other markers as appropriate, assessed in
bronchial biopsies.
* To evaluate the clinical efficacy of 78-weeks therapy with omalizumab
compared to placebo in patients with moderate to severe asthma, based on the
number of clinically significant asthma exacerbations, spirometry, GETE (global
evaluation of treatment effectiveness) after 16 weeks treatment, FENO
(fractional exhaled nitric oxide) and asthma control as measured by the Asthma
Control Questionnaire (ACQ).
* To evaluate the effect of 52 and 76-weeks therapy with omalizumab compared to
placebo on markers of airway inflammation such as eosinophils and chemokines
and cytokines, in induced sputum.
* To evaluate the correlation of the bronchial biopsy parameters with clinical
efficacy and markers of systemic inflammation (such as the number of
circulating eosinophils and free IgE) after 78-weeks therapy with omalizumab
compared to placebo.
* To conduct exploratory pharmacogenomic studies to identify gene expression
patterns, proteins, and metabolites of blood that are associated with treatment
response to omalizumab, or that possibly correlate with the severity or
progression of asthma.
* To conduct exploratory analyses of serum cytokines and markers of systemic
inflammation that are associated with treatment response to omalizumab or that
possibly correlate with the severity or progression of asthma.
Secondary outcome
see above
Background summary
Xolair is a medication called a monoclonal antibody. It works by blocking one
of the body*s chemicals involved in lung inflammation in patients with allergic
asthma. Xolair has been shown to reduce asthma symptoms and to decrease the
incidence of asthma exacerbations.
The main reason for this study is to find out if Xolair works by reducing
inflammation of the airways that causes your asthma to get worse.
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.
Study objective
* Primary objective: To determine the effect of 78-weeks therapy with
omalizumab compared to placebo on the number of sub-epithelial eosinophils, a
marker of airway inflammation, in patients with persistent moderate to severe
allergic asthma.
* Secondary objectives: To evaluate the effect of 78-weeks therapy with
omalizumab compared to placebo on sub-epithelial mast cells and CD4+
T-lymphocytes, as markers of airway inflammation and the thickness of the
reticular basement membrane, as a marker of airway remodeling, assessed in
bronchial biopsies.
To evaluate the safety and tolerability of 78-weeks therapy with omalizumab
compared to placebo.
Study design
This is an international, multi-center, randomized, double-blind,
placebo-controlled, parallel group study to explore the effects of 78-weeks
omalizumab therapy on markers of airway inflammation and remodeling in patients
with persistent moderate to severe asthma. Patients entered into this study are
18-60 years old diagnosed with moderate to severe allergic asthma with
persistent airway inflammation and persistent symptoms, despite treatment with
high doses of inhaled corticosteroid (>= 800 µg per day beclomethasone
diproprionate [BDP] or equivalent total ex-valve dose) and long acting β-2
agonists [LABA] (as either fixed or separate combination treatment).
Study burden and risks
Skin prick testing results in very few allergic reactions involving the entire
body and is generally considered to be the most convenient method for detecting
allergies.
The blood test is a routine procedure which may cause temporary discomfort or
slight bruising at the site of blood drawing or fainting. During collection of
blood samples, patients may experience pain and/or bruising at the site on your
arm where blood is taken. Localized blood clotting and infections may occur,
but this is rare.
When patients are given a dose of study medication they may experience
temporary discomfort or bruising at some or all of the places where you receive
the injections in your arm.
On rare occasions it is possible that a bronchoscopy procedure causes
bronchospasm (tightening in your lung passages), hypoxaemia (a fall in the
amount of oxygen in your blood), fever, allergic reactions to local
anaesthetics and bleeding. Complications can be cough, hoarseness, collapsed
lung, and bleeding from the sample site.
It is possible that an induced sputum collection procedure causes bronchospasm
(tightening in your lung passages).
Lichtstrasse 35
4056 Basel
CH
Lichtstrasse 35
4056 Basel
CH
Listed location countries
Age
Inclusion criteria
1. patients who are 18 - 60 years of age
2. with a body weight >= 20 kg and <= 150 kg and with a serum total IgE level >= 30 to <= 700 IU/ml. The combination of body weight and serum total IgE level must fall within the dosing cells of the approved European dosing table
3. patients with moderate to severe allergic asthma, with persistent symptoms despite receiving an inhaled corticosteroid and long acting beta-agonist (i.e. Step 4 or 5 treatment as per 2006 GINA guidelines - Appendix 3)
4. with >= 2% eosinophilia in induced sputum at visits 1 and 2
5. 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. In addition a RAST test may be performed for patients with a borderline skin prick test result. Patients with a total IgE level of <= 76 IU require an unequivocal positive RAST test (>=71 IU/mL) to be eligible. Skin prick test procedures can be found in Appendix 7
6. with FEV1 *60% of the predicted normal value for the patient (demonstrable at least 6 hours after last short acting β-2 agonist use and 12 hours after last long β-2 acting agonist use) at Visit 1. FEV1 % predicted must be stable at the second screening visit (Visit 2) and the randomization visit (Visit 3) (within 10%)
7. receiving high dose inhaled corticosteroid >= 800µg per day BDP or equivalent, as monotherapy or fixed dose combination, and a regular inhaled long acting β-2 agonist at stable doses for at least 3 months prior to screening
Exclusion criteria
1. Other therapies/medication:
• who are receiving:
• ß adrenergic antagonist medication (e.g.: propranolol) or anticipate use during the study
• methotrexate, gold salts, cyclosporin or troleandomycin within 3 months of Visit 1 or anticipate their use during the study
• desensitization therapy with less than 3 months of stable maintenance doses prior to the screening visit (Visit 1)
• maintenance systemic corticosteroids
• leukotriene receptor antagonists, theophylline or oral or inhaled anticholinergics
• who have received omalizumab previously
2. Concurrent diseases/conditions and history of other diseases/conditions:
• who have been treated for an asthma exacerbation during the 4 weeks prior to randomization
• who are current smokers, or have a smoking history > 10 pack years
• with elevated serum IgE levels for reasons other than allergy (e.g.: parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or clinical allergic bronchopulmonary aspergillosis)
3. Ingredient hypersensitivity:
• with known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g.: monoclonal antibodies, polyclonal gamma globulin)
4. Exclusion criteria for flexible fiberoptic bronchoscopy:
• history of allergic reactions to local anesthetics to be used in the procedure
• any clotting abnormality (e.g. abnormal platelet count)
• recent acute myocardial infarction, unstable angina and other relevant medical conditions deemed appropriate by the investigator
• history of chronic CO2 retention
• a patient is considered to be unsuitable for bronchoscopy, according to the judgment of the investigator
• a patient who has been intubated because of their asthma
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-004653-29-NL |
| CCMO | NL21894.058.08 |