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

March 19, 2015 updated by: Gail Gauvreau, Hamilton Health Sciences Corporation
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Cardio- Respiratory Research Laboratory, Hamilton Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allergen Challenge
Procedure: Bone Marrow Aspiration
3 per study
Procedure: Tonsil Biopsy
Optional upon completion of study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Within 7 days of allergen challenge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hamilton Health Sciences Corporation

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Gail M Gauvreau, PhD, McMaster Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

August 17, 2011

First Submitted That Met QC Criteria

August 18, 2011

First Posted (Estimate)

August 19, 2011

Study Record Updates

Last Update Posted (Estimate)

March 20, 2015

Last Update Submitted That Met QC Criteria

March 19, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MAC-GNE-07222011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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