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

Hamilton Health Sciences (HHS)

Status

Completed

Conditions

Atopic Asthma

Treatments

Procedure: Tonsil Biopsy

Procedure: Bone Marrow Aspiration

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01420003

MAC-GNE-07222011

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.