A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma

Abstract

Background: Preclinical studies suggest that interleukin-9 may be a central mediator in the development and maintenance of airway inflammation in asthma. The aim of this study was therefore to evaluate the effects of MEDI-528, an anti-interleukin-9 monoclonal antibody, in adults with confirmed uncontrolled moderate-to-severe asthma.

Methods: In this prospective double-blind, multicenter, parallel-group study, 329 subjects were randomized (1:1:1:1) to subcutaneous placebo or MEDI-528 (30, 100, 300 mg) every 2 weeks for 24 weeks, in addition to their usual asthma medications. The primary endpoint was change in mean Asthma Control Questionnaire-6 (ACQ-6) score at week 13. Secondary endpoints included weighted asthma exacerbation rates and pre-bronchodilator forced expiratory volume in 1 second (FEV1) at weeks 13 and 25, as well as Asthma Quality of Life Questionnaire scores at weeks 12 and 25 and the safety of MEDI-528 throughout the study period. The primary endpoint was analyzed using analysis of covariance.

Results: The study population (n = 327) was predominantly female (69%) with a mean age of 43 years (range 18-65). The mean (SD) baseline ACQ-6 score for placebo (n = 82) and combined MEDI-528 (n = 245) was 2.8 (0.7) and 2.8 (0.8); FEV1 % predicted was 70.7% (15.9) and 71.5% (16.7). Mean (SD) change from baseline to week 13 in ACQ-6 scores for placebo vs combined MEDI-528 groups was -1.2 (1.0) vs -1.2 (1.1) (p = 0.86). Asthma exacerbation rates (95% CI) at week 25 for placebo vs MEDI-528 were 0.58 (0.36-0.88) vs 0.49 (0.37-0.64) exacerbations/subject/year (p = 0.52). No significant improvements in FEV1 % predicted were observed between the placebo and MEDI-528 groups. Adverse events were comparable for placebo (82.9%) and MEDI-528 groups (30 mg, 76.5%; 100 mg, 81.9%; 300 mg, 85.2%). The most frequent were asthma (placebo vs MEDI-528, 30.5% vs 33.5%), upper respiratory tract infection (14.6% vs 17.1%), and headache (9.8% vs 9.8%).

Conclusions: The addition of MEDI-528 to existing asthma controller medications was not associated with any improvement in ACQ-6 scores, asthma exacerbation rates, or FEV1 values, nor was it associated with any major safety concerns.

Trial registration: ClinicalTrials.gov: NCT00968669.

Figure 1

Study design. ^aInhaled corticosteroids at stable dose: fluticasone/salmeterol (500 μg/50 μg or 250 μg/50 μg) or budesonide/formoterol (160 μg/4.5 μg). ^bSubjects with clinically stable asthma could reduce their inhaled corticosteroid dose to: fluticasone/salmeterol (250 μg/50 μg or 100 μg/50 μg) or budesonide/formoterol (80 μg/4.5 μg). Abbreviations: ACQ-6, Asthma Control Questionnaire-6; FEV₁, Forced expiratory volume in 1 second; s.c, Subcutaneous.

Figure 2

Subject disposition.

Figure 3

Mean (SE) change from baseline in mean ACQ-6 score at weeks 13 and 25 (ITT population). Abbreviations: ACQ-6, Asthma Control Questionnaire-6; ITT, Intent-to-treat; SE, Standard error.

Figure 4

Weighted rate of asthma exacerbation (95% CI) at week 25 (ITT population). Abbreviation: ITT, Intent-to-treat.

Figure 5

Mean (SE) change from baseline in pre-bronchodilator FEV1 at week s 13 and 25 (ITT population). Abbreviations: FEV₁, Forced expiratory volume in 1 second; ITT, Intent-to-treat; SE, Standard error.