Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma

Abstract

Objectives We wished to evaluate the effects of an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody (KB003) on forced expiratory volume in 1 s (FEV₁), asthma control and asthma exacerbations in adult asthmatics inadequately controlled by long-acting bronchodilators and inhaled/oral corticosteroids. Settings 47 ambulatory asthma care centres globally. Primary outcome measures Change in FEV₁ at week 24. Participants 311 were screened, 160 were randomised and 129 completed the study. Interventions 7 intravenous infusions of either 400 mg KB003 or placebo at baseline and weeks 2, 4, 8, 12, 16 and 20. Primary and secondary outcome measures FEV₁ at week 24, asthma control, exacerbation rates and safety in all participants as well as prespecified subgroups. Main results In the KB003 treated group, FEV₁ at week 24 improved to 118 mL compared with 54 mL in the placebo group (p=0.224). However, FEV₁ improved to 253 vs 26 mL at week 24 (p=0.02) in eosinophilic asthmatics (defined as >300 peripheral blood eosinophils/mL at baseline) and comparable improvements were seen at weeks 20 (p=0.034) and 24 (p=0.077) in patients with FEV₁ reversibility ≥20% at baseline and at weeks 4 (p=0.029), 16 (p=0.018) and 20 (p=0.006) in patients with prebronchodilator FEV₁ ≤50% predicted at baseline. There were no effects on asthma control or exacerbation rates. The most frequent adverse events in the KB003 group were rhinosinusitis and headache. There was no significant difference in antidrug antibody response between placebo and treated groups. There were no excess infections or changes in biomarkers known to be associated with the development of pulmonary alveolar proteinosis. Conclusions Higher doses and/or further asthma phenotyping may be required in future studies with KB003. Trial registration number NCT01603277; Results.