Kinetics of IgE Memory B Cells, Plasmablasts and Plasma Cells After Whole Lung Allergen Challenge in Mild Asthmatics

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Gail Gauvreau, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01420003
First received: August 17, 2011
Last updated: November 23, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to characterize the time course of B cell activation after allergen challenge, and more specifically measure the M1 prime related biomarkers.


Condition Intervention
Atopic Asthma
Procedure: Bone Marrow Aspiration
Procedure: Tonsil Biopsy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Kinetics of IgE Memory B Cells, Plasmablasts and Plasma Cells After Whole Lung Allergen Challenge in Mild Asthmatics

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • To characterize the time course of B cell activation after allergen challenge, and more specifically measure the M1 prime related biomarkers. [ Time Frame: Within 7 days of allergen challenge ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: November 2011
Estimated Study Completion Date: December 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allergen Challenge Procedure: Bone Marrow Aspiration
3 per study
Procedure: Tonsil Biopsy
Optional upon completion of study

Detailed Description:

M1 prime is a segment of IgE found only in the membrane form of IgE and not on soluble IgE found in serum. Membrane IgE (and M1prime) is expressed on IgE-switched B cells, IgE-memory B cels, and IgE-plasmablasts. Depletion of IgE-switched B cells and plasmablasts will reduce IgE-producing cells and serum IgE, and may be a target for treatment of allergic asthma. A humanized antibody targeting M1 prime is being developed by Genentech, Inc., as a potential therapeutic for asthma.

Currently, the efficacy of MEMP1972A is being assessed in an allergen challenge study in mild asthmatics (MOP4843g). Extensive biomarker samples have been incorporated in that study to characterize the mechanism of action (MOA) as well as the kinetics of the MOA of MEMP1972A, which are poorly understood at this time. Furthermore, samples for the B cell enriched peripheral blood flow cytometry and bone marrow aspirates to evaluate the kinetics and MOA of MEMP1972a are collected only 24 hr after allergen challenge due to visit and sample volume limitations. It is known that maximal B cell responses are expected ~7 days after allergen stimulation. Therefore, the purpose of this research study will be to characterize the time course of B cell activation after allergen challenge, and more specifically measure the M1 prime related biomarkers.

  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.
  • Females must not be actively seeking pregnancy, must be using adequate and effective contraception
  • 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
  • History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness
  • History or symptoms of clinically significant autoimmune disease
  • History of clinically significant hematologic abnormality, including coagulopathy
  • Be pregnant or lactating
  • 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: NCT01420003

Locations
Canada, Ontario
Cardio- Respiratory Research Laboratory, Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Genentech
Investigators
Principal Investigator: Gail M Gauvreau, PhD McMaster Health Sciences
  More Information

Additional Information:
Publications:

Responsible Party: Gail Gauvreau, Gail Gauvreau, PhD, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01420003     History of Changes
Other Study ID Numbers: MAC-GNE-07222011
Study First Received: August 17, 2011
Last Updated: November 23, 2012
Health Authority: Canada: Health Canada

Keywords provided by Hamilton Health Sciences Corporation:
Allergen Challenge
B cell activation
M1 prime related biomarkers

ClinicalTrials.gov processed this record on September 18, 2014