The Prednisone-sparing Effect of Anti-IL-5 Antibody (SB-240563)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
St. Joseph's Healthcare Hamilton
ClinicalTrials.gov Identifier:
NCT00292877
First received: February 15, 2006
Last updated: January 21, 2011
Last verified: January 2011
  Purpose

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).


Condition Intervention Phase
Asthma
Drug: SB-240563 (Mepolizumab)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by St. Joseph's Healthcare Hamilton:

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.

Estimated Enrollment: 20
Study Start Date: January 2005
Study Completion Date: July 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. On the same doses of corticosteroids for a least one-month.

Exclusion Criteria:

  1. Pregnancy, breast-feeding or lack of effective contraception in females of childbearing potential or females who are postmenopausal <1 year.
  2. 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.
  3. Exposure to a relevant seasonal environmental allergen, known to worsen asthma control, during the study period.
  4. Respiratory tract infection in the 4-weeks before the baseline visit.
  5. Clinical exacerbation requiring extra prednisone treatment in the 4-weeks before V1.
  6. Other cardiac, pulmonary, renal or systemic diseases that in the investigator's opinion may interfere with the study results or compromise subject's safety.
  7. Previous participation in any study using anti-monoclonal drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00292877

Locations
Canada, Ontario
Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada, L8N 4A6
Sponsors and Collaborators
St. Joseph's Healthcare Hamilton
GlaxoSmithKline
Investigators
Principal Investigator: Frederick E Hargreave, MD McMaster University
  More Information

Publications:
Sanderson CJ. The biological role of interleukin 5. Int J Cell Cloning 1990; 8: 147-53.
Djukanovic R, Roche WR, Wilson JW, et al. Mucosal inflammation in asthma: state of the art. Am Rev Respir Dis 1990; 142: 434-457.
Djukanovic R, Sterk PJ, Fahy JV, Hargreave FE. Standardized methodology of sputum induction and processing. Eur Respir J 2002; 20: Suppl 37, 1S-55s.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00292877     History of Changes
Other Study ID Numbers: RP#02-2115, SB-240563/046, 9427-F2453-21C
Study First Received: February 15, 2006
Last Updated: January 21, 2011
Health Authority: Canada: Health Canada

Keywords provided by St. Joseph's Healthcare Hamilton:
1. Eosinophilic bronchitis, 2. Asthma, 3. Steroid dependent asthma, 4. Sputum eosinophils, 5. SB-240563 (Mepolizumab)

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014