title: 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: OBJECTIVE
  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.
  
  
  METHODS
  47 ambulatory asthma care centres globally.
  
  
  METHODS
  Change in FEV1 at week 24.
  
  
  METHODS
  311 were screened, 160 were randomised and 129 completed the study.
  
  
  METHODS
  7 intravenous infusions of either 400 mg KB003 or placebo at baseline and weeks 2, 4, 8, 12, 16 and 20.
  
  
  METHODS
  FEV1 at week 24, asthma control, exacerbation rates and safety in all participants as well as prespecified subgroups.
  
  
  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.
  
  
  BACKGROUND
  NCT01603277; Results.
authors.affiliation: Drug Development Consultant, San Francisco, California, USA.
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
authors.affiliation: Barlicki University Hospital, Medical University of Lodz, Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
authors.affiliation: InterMune, Inc., Brisbane, California, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Leff
authors.affiliation: Glenmark Pharmaceuticals, Mahwah, New Jersey, USA.
authors.forename: Chad K
authors.initials: CK
authors.lastname: Oh
authors.affiliation: Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester Foundations Trust, Manchester, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Drug Development Consultant, San Francisco, California, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Chernow
authors.affiliation: Chiltern International, Berkshire, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Sutton
authors.affiliation: Drug Development Consultant, San Francisco, California, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Yarranton
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D001993:Bronchodilator Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: THORACIC MEDICINE