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


BACKGROUND
ClinicalTrials.gov: NCT00968669.
MedImmune, One MedImmune Way, Gaithersburg, MD, USA. hultquistm@medimmune.com.
Chad K
CK
Oh
Richard
R
Leigh
Kimmie K
KK
McLaurin
Keunpyo
K
Kim
Micki
M
Hultquist
Nestor A
NA
Molfino
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016906:Interleukin-9; C542276:enokizumab