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

• Sponsor: St. Joseph's Healthcare Hamilton (Other)
• Overall Status: Completed
• CT.gov ID: NCT00292877
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 20
• Location: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.5

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: SB-240563 (Mepolizumab)	Phase 2

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.

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• 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
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Outcome Measures

Primary Outcome Measures

1. The prednisone-sparing effect of SB-240563 versus placebo as []

2. 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

1. The prednisone-sparing effect of SB-240563 or placebo as indicated []

2. by the absolute and percentage dose reduction possible without a clinical []

3. exacerbation as measured by []

4. a.% sputum eosinophils, b. FEV1 % predicted and methacholine PC20., c. Blood eosinophils, d. Amount of rescue salbutamol use., e. Time to exacerbation. []

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Djukanović 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. Review.
• Djukanović R, Sterk PJ, Fahy JV, Hargreave FE. Standardised methodology of sputum induction and processing. Eur Respir J Suppl. 2002 Sep;37:1s-2s.
• 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.
• Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999 Jun 26;353(9171):2213-4.
• Sanderson CJ. The biological role of interleukin 5. Int J Cell Cloning. 1990 Jan;8 Suppl 1:147-53; discussion 153-4. Review.

• ClinicalTrials.gov Identifier: NCT00292877
• Other Study ID Numbers: RP#02-2115; SB-240563/046; 9427-F2453-21C
• First Posted: Feb 16, 2006
• Last Update Posted: Jan 24, 2011
• Last Verified: Jan 1, 2011

• Keywords provided by , ,: 1. Eosinophilic bronchitis, 2. Asthma, 3. Steroid dependent asthma, 4. Sputum eosinophils, 5. SB-240563 (Mepolizumab)
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Jan 24, 2011