OX40L blockade and allergen-induced airway responses in subjects with mild asthma.
Clin Exp Allergy
; 44(1): 29-37, 2014 Jan.
Article
in En
| MEDLINE
| ID: mdl-24224471
ABSTRACT
BACKGROUND:
The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.OBJECTIVE:
We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma.METHODS:
Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-group trial (ClinicalTrials.gov identifier NCT00983658) to compare blockade of OX40L using a humanized anti-OX40L MAb to placebo-administered intravenously in 4 doses over 3 months. Allergen inhalation challenges were carried out 56 and 113 days after the first dose of study drug. The primary outcome variable was the late-phase asthmatic response. Other outcomes included the early-phase asthmatic response, airway hyperresponsiveness, serum IgE levels, blood and sputum eosinophils, safety and tolerability.RESULTS:
Treatment with anti-OX40L MAb did not attenuate the early- or late-phase asthmatic responses at days 56 or 113 compared with placebo. In the anti-OX40L MAb treatment group, total IgE was reduced 17% from pre-dosing levels, and sputum eosinophils decreased 75% by day 113 (both P = 0.04). There was no effect of anti-OX40L MAb on airway hyperresponsiveness or blood eosinophils. The frequency of AEs was similar in both groups. CONCLUSION AND CLINICAL RELEVANCE Pharmacological activity of anti-OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post-dosing, but there was no effect on allergen-induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Asthma
/
Allergens
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Anti-Asthmatic Agents
/
CD40 Ligand
/
Antibodies, Monoclonal
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Year:
2014
Type:
Article