Omalizumab in Non-atopic Asthma
Primary Purpose
Bronchial Asthma
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Omalizumab
Placebo
Sponsored by

About this trial
This is an interventional treatment trial for Bronchial Asthma focused on measuring Bronchial Asthma, Allergy
Eligibility Criteria
Inclusion criteria-
- Males and females aged 18 to 60 years inclusive.
- Moderate or severe non-atopic asthma as defined below treated with inhaled corticosteroids for at least 6 months.
- Daytime and nighttime symptoms at least 3 days per week in the last 3 months prior to screening visit(despite taking inhaled corticosteroids with or without beta-2-agonists or leukotriene blockers.
- Pre-bronchodilator FEV1 40-80% of the predicted; reversibility equal to or more than 12% in response to inhaled beta-2-agonists documented at any time within the past 2 years.
- Negative skin prick and/or in vitro IgE tests to a range of 12 common aeroallergens(pollens:grass, hazel, alder, birch; danders: cat, dog; dust mite: D.pteronyssinus, D.farinae; moulds: Cladosporium, Aspergillus, Alternaria).
Exclusion Criteria
- Smoking within the past year or total smoking history more than 0.5 pack years.
- Pregnant or lactating females or those at risk of pregnancy.
- Treatment with more than 2000 mcg/day beclometasone, 1600 mcg/day budesonide or 1000 mcg/day fluticasone by inhalation or regular systemic corticosteroid at screening.
- Hospitalization for asthma or exacerbation requiring systemic corticosteroid therapy within 3 months of the screening visit.
- History of life threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
- Patients in whom, in the opinion of the study investigators, omalizumab therapy might normally require precaution (history of autoimmune disease, renal or hepatic impairment, hyperimmunoglobulin E syndrome, allergic bronchopulmonary aspergillosis and diabetes mellitus)
Sites / Locations
- London Chest Hospital
- Guy's Hospital, London, UKRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Omalizumab
Placebo
Arm Description
There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.
There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.
Outcomes
Primary Outcome Measures
Pre-bronchodilator FEV1
Prior to reduction of existing anti-asthma therapy (first 12 weeks of study):
• Pre-bronchodilator FEV1 (primary outcome measure)
Disease exacerbation
During anti-asthma therapy reduction phase (subsequent 8 weeks of study):
The primary outcome measure during asthma therapy reduction phase 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
Day and night time symptom scores
These will be measured using standard Asthma Control Questionnaires(ACQ)
Morning and evening peakflows
Exhaled nitric oxide
Total dosage of rescue beta-2-agonists
Total symptom free days
Quality of life scores
Markers of airway remodelling and inflammation
These include- Collagen,tenascin,VEGF,CD31,inflammatory cells,goblet cells etc.
Local IgE synthesis in the bronchial mucosa and its expression
The measurement will include- IgE, its low and high affinity receptors, expression of free kappa and lambda light chains on B-cells and plasma cells
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01113437
Brief Title
Omalizumab in Non-atopic Asthma
Official Title
The Effect of a Humanised Monoclonal Anti-IgE Antibody,Omalizumab, on Disease Control and Bronchial Mucosal Inflammation in Non-atpic Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2010
Overall Recruitment Status
Unknown status
Study Start Date
April 2010 (undefined)
Primary Completion Date
August 2012 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
King's College London
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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).
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchial Asthma
Keywords
Bronchial Asthma, Allergy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Omalizumab
Arm Type
Experimental
Arm Description
There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
There are 2 arms of the study; patients in one arm receiving omalizumab and in the other arm receiving placebo.
Intervention Type
Drug
Intervention Name(s)
Omalizumab
Other Intervention Name(s)
Xolair
Intervention Description
Omalizumab or placebo by subcutaneous injections, at 4 weekly or 2 weekly intervals.
Dosage is according to manufacturer's guidance and calculated based on body weight and total serum IgE.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Omalizumab or placebo by subcutaneous injections, at 4 weekly or 2 weekly intervals.
Dosage is according to manufacturer's guidance and calculated based on body weight and total serum IgE.
Primary Outcome Measure Information:
Title
Pre-bronchodilator FEV1
Description
Prior to reduction of existing anti-asthma therapy (first 12 weeks of study):
• Pre-bronchodilator FEV1 (primary outcome measure)
Time Frame
before and after treatment with omalizumab for 16 weeks
Title
Disease exacerbation
Description
During anti-asthma therapy reduction phase (subsequent 8 weeks of study):
The primary outcome measure during asthma therapy reduction phase 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
Time Frame
From week 12 to week 20 of the study
Secondary Outcome Measure Information:
Title
Day and night time symptom scores
Description
These will be measured using standard Asthma Control Questionnaires(ACQ)
Time Frame
before and after treatment with omalizumab for 16 weeks
Title
Morning and evening peakflows
Time Frame
before and after treatment with omalizumab for 16 weeks
Title
Exhaled nitric oxide
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
Title
Total dosage of rescue beta-2-agonists
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
Title
Total symptom free days
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
Title
Quality of life scores
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
Title
Markers of airway remodelling and inflammation
Description
These include- Collagen,tenascin,VEGF,CD31,inflammatory cells,goblet cells etc.
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
Title
Local IgE synthesis in the bronchial mucosa and its expression
Description
The measurement will include- IgE, its low and high affinity receptors, expression of free kappa and lambda light chains on B-cells and plasma cells
Time Frame
before and after treatment with omalizumab for 16 weeks(from week 0 to week 16)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria-
Males and females aged 18 to 60 years inclusive.
Moderate or severe non-atopic asthma as defined below treated with inhaled corticosteroids for at least 6 months.
Daytime and nighttime symptoms at least 3 days per week in the last 3 months prior to screening visit(despite taking inhaled corticosteroids with or without beta-2-agonists or leukotriene blockers.
Pre-bronchodilator FEV1 40-80% of the predicted; reversibility equal to or more than 12% in response to inhaled beta-2-agonists documented at any time within the past 2 years.
Negative skin prick and/or in vitro IgE tests to a range of 12 common aeroallergens(pollens:grass, hazel, alder, birch; danders: cat, dog; dust mite: D.pteronyssinus, D.farinae; moulds: Cladosporium, Aspergillus, Alternaria).
Exclusion Criteria
Smoking within the past year or total smoking history more than 0.5 pack years.
Pregnant or lactating females or those at risk of pregnancy.
Treatment with more than 2000 mcg/day beclometasone, 1600 mcg/day budesonide or 1000 mcg/day fluticasone by inhalation or regular systemic corticosteroid at screening.
Hospitalization for asthma or exacerbation requiring systemic corticosteroid therapy within 3 months of the screening visit.
History of life threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
Patients in whom, in the opinion of the study investigators, omalizumab therapy might normally require precaution (history of autoimmune disease, renal or hepatic impairment, hyperimmunoglobulin E syndrome, allergic bronchopulmonary aspergillosis and diabetes mellitus)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christopher Corrigan, MD,PhD
Phone
00-44-2071880610
Email
chris.corrigan@kcl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Prathap Pillai, MD
Phone
00-44-2071880606
Email
prathap.pillai@kcl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Corrigan, MD, PhD
Organizational Affiliation
King's College, London, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neil Barnes, MD
Organizational Affiliation
London Chest Hospital, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Prathap Pillai, MD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
London Chest Hospital
City
London
ZIP/Postal Code
E2 9JX
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neil Barnes, MD
Phone
02089832433
Email
neil.barnes@bartsandthelondon.nhs.uk
First Name & Middle Initial & Last Name & Degree
Neil Barnes, MD
Facility Name
Guy's Hospital, London, UK
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Corrigan, MD,PhD
Phone
00-44-2071880610
Email
chris.corrigan@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
Prathap Pillai, MD
Phone
00-44-2071880606
Email
prathap.pillai@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
Chris Corrigan, MD,PhD
First Name & Middle Initial & Last Name & Degree
Prathap Pillai, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
27824606
Citation
Pillai P, Chan YC, Wu SY, Ohm-Laursen L, Thomas C, Durham SR, Menzies-Gow A, Rajakulasingam RK, Ying S, Gould HJ, Corrigan CJ. Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma. Eur Respir J. 2016 Dec;48(6):1593-1601. doi: 10.1183/13993003.01501-2015. Epub 2016 Oct 20.
Results Reference
derived
Learn more about this trial
Omalizumab in Non-atopic Asthma
We'll reach out to this number within 24 hrs