CSL311 and Cell Viability in Asthma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Hamilton Health Sciences Corporation
Sponsor:
Collaborator:
CSL Limited
Information provided by (Responsible Party):
Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01759849
First received: December 17, 2012
Last updated: October 9, 2013
Last verified: October 2013
  Purpose

To examine the effect of blocking signaling through the β-chain on viability, activation and differentiation of eosinophils and their progenitors collected from sputum, blood and bone marrow samples collected pre and post-allergen challenge from mild atopic asthmatic subjects.


Condition Intervention Phase
Asthma
Drug: CSL 311
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of in Vitro CSL311 on the Function of Blood, Bone Marrow and Sputum Cells From Asthmatic Donors.

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • Sputum Collection [ Time Frame: 7 hrs post allergen ] [ Designated as safety issue: No ]
    Three baseline sample collections will ensure sufficient numbers of cells are collected for proposed outcomes. Post allergen cells will be examined at time points when these populations are known to be at their highest frequency.


Estimated Enrollment: 10
Study Start Date: November 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CSL311
CSL 311 will determine the effects of a β-chain monoclonal antibody (MAb) on the function of cells naturally activated by in vivo allergen exposure, from donors with allergen-induced asthma
Drug: CSL 311
CSL311 is a humanized monoclonal antibody targeting the common beta chain receptor to IL-3, IL-5 and GM-CSF, which is present on select leukocytes including eosinophils.

Detailed Description:

The experiments will use sputum samples induced from subjects with mild asthma, undergoing allergen inhalation challenges. In general, each sample will be composed of >10% neutrophils and >10% macrophages. Samples collected pre-allergen will have a low frequency of eosinophils and lymphocytes (<1%), however the percentage of eosinophils will increase to approximately 12% following allergen challenges. The sputum samples will be processed in DPBS (without dithiothreitol), and the cell suspension will be adjusted to 1 million cells/ml in DMEM with penicillin and streptomycin. A cytospin will be made for differential cell counts. The mixed cell population at 5 million cells/ml will be incubated for 48 hours at 37 degrees Celcius ± β-chain MAb at a concentration of 100 mcg/ml. After 48 hours the cell culture medium will be removed for assay of cytokines and chemokines by ELISA. Cells will be resuspended in PBS and Binding Buffer (BD Pharmingen, Cat no. 556454),stained for assessments by flow cytometry, and analyzed in duplicate.

Experiments will use blood (80 ml) and bone marrow aspirates (5ml) from atopic asthmatics taken pre and 24hr post allergen challenge. Methylcult micro-culture colonogenic assays will be performed to enumerate outgrowth of Eo/Baso-CFU and GM-CFU from CD34+ cells populations collected from the blood and bone marrow samples. Methylcult assays will be performed with CD34+ enriched cell populations in the presence of IL-5,IL-3 and GM-CSF +/- CSL311. Following 14 days culture, colonies will be enumerated.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female volunteers 18 through 65 years of age.
  • General good health
  • Mild to moderate, stable, allergic asthma
  • History of episodic wheeze and shortness of breath; FEV1 at baseline at least 70% of the predicted value
  • Able to understand and give written informed consent and has signed a written informed consent form approved by the investigator's REB
  • Positive methacholine challenge
  • Positive skin-prick test to common aeroallergens (including cat, dust mite, grass, pollen)
  • Positive allergen-induced airway bronchoconstriction (a fall in FEV1 of at least 20% from baseline)

Exclusion Criteria:

  • A worsening of asthma or a respiratory tract infection within 6 weeks preceding study entry
  • Use of corticosteroids, immunosuppressives, anticoagulants (warfarin or heparin) within 28 days prior to randomization into the study
  • Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of dosing or aspirin with 7 days of dosing
  • Have chronic use of any other medication for treatment of allergic lung disease other than short- and intermediate-acting ß2-agonists or ipratropium bromide
  • Use of caffeine-containing products or medications for 12 hours or alcohol or over the counter drugs including aspirin, cold and allergy medications for 48 hours or inhaled bronchodilators for 8 hours prior to methacholine and allergen challenges
  • Use of tobacco products of any kind currently or within the previous 12 months, or smoking history > 10 pack years.
  • Lung disease other than mild to moderate allergic asthma
  • Unwillingness or inability to comply with the study protocol for any other reason.
  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: NCT01759849

Contacts
Contact: Gail Gauvreau, PhD 605-525-9140 ext 22791 gauvreau@mcmaster.ca

Locations
Canada, Ontario
McMaster Medical Center Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Gail M Gauvreau, PhD    905-525-9140 ext 22791    gauvreau@mcmaster.ca   
Principal Investigator: Gail M Gauvreau, PhD         
Sponsors and Collaborators
Hamilton Health Sciences Corporation
CSL Limited
Investigators
Principal Investigator: Gail M Gauvreau, PhD Hamilton Health Sciences Corporation
  More Information

No publications provided

Responsible Party: Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01759849     History of Changes
Other Study ID Numbers: CSL311
Study First Received: December 17, 2012
Last Updated: October 9, 2013
Health Authority: Canada: Health Canada

Keywords provided by Hamilton Health Sciences Corporation:
Asthma
β-chain signaling
allergen inhalation challenges
sputum
bone marrow aspirate
blood collection
-methacholine challenge

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 20, 2014