Back to resultsThe Prednisone-sparing Effect of Anti-IL-5 Antibody (SB-240563)
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
SB-240563 (Mepolizumab)
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring 1. Eosinophilic bronchitis, 2. Asthma, 3. Steroid dependent asthma, 4. Sputum eosinophils, 5. SB-240563 (Mepolizumab)
Eligibility Criteria
Inclusion Criteria: Adult patients, aged 18-70 years, who have been followed as an outpatient and who have been found to require a minimum dose of prednisone treatment (in addition to high-dose inhaled steroid treatment) to prevent frequent exacerbations associated with induced sputum eosinophilia. Patients will be enrolled if, at screening and baseline visits, they demonstrate sputum eosinophilia and symptoms. The symptoms may effect activity and sleep but should not, in the opinion of the treating physician, be severe enough to be of concern. While FEV1 after withholding bronchodilators appropriately, before and after inhaled salbutamol (200 mg), and methacholine PC20 will be measured, these need not be abnormal since the prednisone is required for the control of eosinophilic bronchitis and any clinical consequences of this, and because the bronchitis can occur without these features of asthma. On the same doses of corticosteroids for a least one-month. Exclusion Criteria: Pregnancy, breast-feeding or lack of effective contraception in females of childbearing potential or females who are postmenopausal <1 year. Baseline FEV1 before bronchodilator of 40% or less of predicted. This lower FEV1 is acceptable since chronic airflow limitation secondary to the eosinophilic bronchitis or asthma is not an exclusion criteria. Neither is current or ex-cigarette smoking providing that the best FEV1 in these patients has been >60% predicted normal or the best FEV1/VC ratio has been >60% in the past two years. Exposure to a relevant seasonal environmental allergen, known to worsen asthma control, during the study period. Respiratory tract infection in the 4-weeks before the baseline visit. Clinical exacerbation requiring extra prednisone treatment in the 4-weeks before V1. Other cardiac, pulmonary, renal or systemic diseases that in the investigator's opinion may interfere with the study results or compromise subject's safety. Previous participation in any study using anti-monoclonal drug.
Sites / Locations
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton
Outcomes
Primary Outcome Measures
The prednisone-sparing effect of SB-240563 versus placebo as
indicated by the absolute and percentage dose reduction possible without a clinical exacerbation (as measured by the Juniper ACQ in patients with asthma or by Likert symptom scores +/- FEV1 in patients with eosinophilic bronchitis without asthma).
Secondary Outcome Measures
The prednisone-sparing effect of SB-240563 or placebo as indicated
by the absolute and percentage dose reduction possible without a clinical
exacerbation as measured by
a.% sputum eosinophils, b. FEV1 % predicted and methacholine PC20., c. Blood eosinophils, d. Amount of rescue salbutamol use., e. Time to exacerbation.
Full Information
NCT ID
NCT00292877
First Posted
February 15, 2006
Last Updated
January 21, 2011
Sponsor
St. Joseph's Healthcare Hamilton
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00292877
Brief Title
The Prednisone-sparing Effect of Anti-IL-5 Antibody (SB-240563)
Official Title
The Effects of a Humanized Anti-IL-5 Monoclonal Antibody (SB-240563) on Asthma Control, Airway Eosinophilia and the Degree to Which Corticosteroid Treatment Can be Reduced to Maintain Control
Study Type
Interventional
2. Study Status
Record Verification Date
January 2011
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
July 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
St. Joseph's Healthcare Hamilton
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine if treatment with anti-IL-5 antibody has a prednisone-sparing effect in patients with symptomatic eosinophilic bronchitis (with or without asthma).
Detailed Description
Eosinophilic bronchitis, which is identified by quantitative sputum cell counts (eosinophils greater than 2%) is responsive to corticosteroid treatment. It occurs alone or in association with asthma or in some patients with chronic obstructive pulmonary disease (COPD). In most patients the eosinophilic bronchitis responds to treatment with inhaled steroids but in some it requires a minimum dose of prednisone to keep it controlled. At present, there is no outstanding drug which can have a prednisone-sparing effect.
Interleukin (IL)-5 is a cytokine specifically focused on the development, differentiation, recruitment, activation and survival of the eosinophil. The specificity of IL-5 has raised the possibility that blocking it's activity, using humanized monoclonal antibodies, may be useful therapy for eosinophilic bronchitis. Such an antibody (SB-240563) has been introduced for clinical trial. The investigators will compare its effect versus placebo in patients with prednisone-dependant symptomatic eosinophilic bronchitis (with or without asthma) before and after a reduction in prednisone dose to identify if it has a prednisone-sparing effect.
The study is divided into 3 sequential study periods. Period 1: symptomatic eosinophilic bronchitis (with or without asthma) on the same dose of prednisone for 6-weeks or more. Period 2: standardized prednisone reduction (and inhaled steroid if prednisone is discontinued during the study treatment) at intervals of 4-weeks until there is a clinical and eosinophilic exacerbation or bothersome steroid withdrawl effects. Period 3: washout.
The patients will be seen every 2 weeks. Intravenous injections of SB-240563 750mg or placebo will be given at weeks 2,6,10,14 and 18. Doses of prednisone will be reduced in a standard way.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
1. Eosinophilic bronchitis, 2. Asthma, 3. Steroid dependent asthma, 4. Sputum eosinophils, 5. SB-240563 (Mepolizumab)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
20 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
SB-240563 (Mepolizumab)
Primary Outcome Measure Information:
Title
The prednisone-sparing effect of SB-240563 versus placebo as
Title
indicated by the absolute and percentage dose reduction possible without a clinical exacerbation (as measured by the Juniper ACQ in patients with asthma or by Likert symptom scores +/- FEV1 in patients with eosinophilic bronchitis without asthma).
Secondary Outcome Measure Information:
Title
The prednisone-sparing effect of SB-240563 or placebo as indicated
Title
by the absolute and percentage dose reduction possible without a clinical
Title
exacerbation as measured by
Title
a.% sputum eosinophils, b. FEV1 % predicted and methacholine PC20., c. Blood eosinophils, d. Amount of rescue salbutamol use., e. Time to exacerbation.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, aged 18-70 years, who have been followed as an outpatient and who have been found to require a minimum dose of prednisone treatment (in addition to high-dose inhaled steroid treatment) to prevent frequent exacerbations associated with induced sputum eosinophilia.
Patients will be enrolled if, at screening and baseline visits, they demonstrate sputum eosinophilia and symptoms. The symptoms may effect activity and sleep but should not, in the opinion of the treating physician, be severe enough to be of concern.
While FEV1 after withholding bronchodilators appropriately, before and after inhaled salbutamol (200 mg), and methacholine PC20 will be measured, these need not be abnormal since the prednisone is required for the control of eosinophilic bronchitis and any clinical consequences of this, and because the bronchitis can occur without these features of asthma.
On the same doses of corticosteroids for a least one-month.
Exclusion Criteria:
Pregnancy, breast-feeding or lack of effective contraception in females of childbearing potential or females who are postmenopausal <1 year.
Baseline FEV1 before bronchodilator of 40% or less of predicted. This lower FEV1 is acceptable since chronic airflow limitation secondary to the eosinophilic bronchitis or asthma is not an exclusion criteria. Neither is current or ex-cigarette smoking providing that the best FEV1 in these patients has been >60% predicted normal or the best FEV1/VC ratio has been >60% in the past two years.
Exposure to a relevant seasonal environmental allergen, known to worsen asthma control, during the study period.
Respiratory tract infection in the 4-weeks before the baseline visit.
Clinical exacerbation requiring extra prednisone treatment in the 4-weeks before V1.
Other cardiac, pulmonary, renal or systemic diseases that in the investigator's opinion may interfere with the study results or compromise subject's safety.
Previous participation in any study using anti-monoclonal drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederick E Hargreave, MD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
2182734
Citation
Sanderson CJ. The biological role of interleukin 5. Int J Cell Cloning. 1990 Jan;8 Suppl 1:147-53; discussion 153-4. doi: 10.1002/stem.5530080713.
Results Reference
background
PubMed Identifier
11191542
Citation
Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000 Dec 23-30;356(9248):2144-8. doi: 10.1016/s0140-6736(00)03496-6.
Results Reference
background
PubMed Identifier
2200318
Citation
Djukanovic R, Roche WR, Wilson JW, Beasley CR, Twentyman OP, Howarth RH, Holgate ST. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434-57. doi: 10.1164/ajrccm/142.2.434.
Results Reference
background
PubMed Identifier
12361359
Citation
Djukanovic R, Sterk PJ, Fahy JV, Hargreave FE. Standardised methodology of sputum induction and processing. Eur Respir J Suppl. 2002 Sep;37:1s-2s. doi: 10.1183/09031936.02.00000102. No abstract available.
Results Reference
background
PubMed Identifier
10392993
Citation
Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999 Jun 26;353(9171):2213-4. doi: 10.1016/S0140-6736(99)01813-9. No abstract available.
Results Reference
background
PubMed Identifier
19264687
Citation
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435.
Results Reference
derived
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The Prednisone-sparing Effect of Anti-IL-5 Antibody (SB-240563)
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