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

ObjectivesWe 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...

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Bibliographic Details
Published in:BMJ open 2016-01, Vol.6 (1), p.e007709-e007709
Main Authors: Molfino, Nestor A, Kuna, Piotr, Leff, Jonathan A, Oh, Chad K, Singh, Dave, Chernow, Marlene, Sutton, Brian, Yarranton, Geoffrey
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - therapeutic use
Adult
Airway management
Anti-Asthmatic Agents - adverse effects
Anti-Asthmatic Agents - pharmacology
Anti-Asthmatic Agents - therapeutic use
Antibodies, Monoclonal - therapeutic use
Asthma
Asthma - drug therapy
Asthma - immunology
Asthma - physiopathology
Bronchodilator Agents - therapeutic use
Cytokines
Drug dosages
Eosinophils - metabolism
Female
Forced Expiratory Volume
Genotype & phenotype
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
Infusions, Intravenous
Male
Middle Aged
Monoclonal antibodies
Neutrophils
Phenotype
Respiratory Medicine
School dropout programs
Spirometry
Steroids
Trends
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Summary:ObjectivesWe 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.Settings47 ambulatory asthma care centres globally.Primary outcome measuresChange in FEV1 at week 24.Participants311 were screened, 160 were randomised and 129 completed the study.Interventions7 intravenous infusions of either 400 mg KB003 or placebo at baseline and weeks 2, 4, 8, 12, 16 and 20.Primary and secondary outcome measuresFEV1 at week 24, asthma control, exacerbation rates and safety in all participants as well as prespecified subgroups.Main resultsIn 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.ConclusionsHigher doses and/or further asthma phenotyping may be required in future studies with KB003.Trial registration numberNCT01603277; Results.
ISSN:2044-6055
2044-6055
DOI:10.1136/bmjopen-2015-007709