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

NCT ID: NCT01420003

Last Updated: 2015-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-07-31

Brief Summary

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.

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.

Conditions

Atopic Asthma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Allergen Challenge

Group Type: EXPERIMENTAL

Bone Marrow Aspiration

Intervention Type: PROCEDURE

3 per study

Tonsil Biopsy

Intervention Type: PROCEDURE

Optional upon completion of study

Interventions

Bone Marrow Aspiration

3 per study

Intervention Type: PROCEDURE

Tonsil Biopsy

Optional upon completion of study

Intervention Type: PROCEDURE

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Gail Gauvreau

Gail Gauvreau, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gail M Gauvreau, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster Health Sciences

Locations

Cardio- Respiratory Research Laboratory, Hamilton Health Sciences

Hamilton, Ontario, Canada

Countries

Canada

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Other Identifiers

MAC-GNE-07222011

Identifier Type: -

Identifier Source: org_study_id