title: Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids.
abstract: BACKGROUND
  Asthma is a disease with marked heterogeneity in its clinical course and response to treatment. IL-13 is central to type 2 inflammation, which contributes to many key features of asthma. Lebrikizumab is an anti-IL-13 mAb previously reported to significantly improve lung function in patients with inadequately controlled asthma despite inhaled corticosteroid therapy, especially in periostin-high patients.
  
  
  OBJECTIVE
  This phase II study investigated the efficacy and safety of IL-13 blockade with different doses of lebrikizumab in asthmatic patients not receiving inhaled corticosteroids.
  
  
  METHODS
  Patients were randomized to receive 125, 250, or 500 mg of lebrikizumab or placebo subcutaneously monthly for 12 weeks with an 8-week follow-up period. The primary efficacy end point was the relative change in prebronchodilator FEV1 from baseline to week 12.
  
  
  RESULTS
  A total of 212 patients were randomized. The mean relative change in FEV1 was numerically higher in all lebrikizumab dose groups versus the placebo group, although the difference was neither statistically nor clinically significant. There were no meaningful differences in changes in FEV1 between the dose groups and the placebo group by the periostin subgroup. Lebrikizumab treatment was associated with a reduced risk of treatment failure at all doses versus placebo (P < .001), and results were similar by the periostin subgroup, with no apparent differences between doses of lebrikizumab. Lebrikizumab was generally well tolerated.
  
  
  CONCLUSIONS
  Blocking IL-13, a single cytokine, in this population of asthmatic patients is insufficient to improve lung function. There is evidence that IL-13 blockade may improve disease control, as measured by prevention of protocol-defined treatment failure in these patients.
authors.affiliation: Allergy Associates Research, Portland, Ore.
authors.forename: Michael
authors.initials: M
authors.lastname: Noonan
authors.affiliation: Clinical Research Center LLC, St Louis, Mo.
authors.forename: Phillip
authors.initials: P
authors.lastname: Korenblat
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mosesova
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Heleen
authors.initials: H
authors.lastname: Scheerens
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Putnam
authors.affiliation: 3-V Biosciences, Menlo Park, Calif.
authors.forename: Merdad V
authors.initials: MV
authors.lastname: Parsey
authors.affiliation: Genentech, South San Francisco, Calif.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Bohen
authors.affiliation: Genentech, South San Francisco, Calif. Electronic address: matthews.john@gene.com.
authors.forename: John G
authors.initials: JG
authors.lastname: Matthews
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D054414:Chemokine CCL17 / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D007958:Leukocyte Count; D008297:Male; D018945:Monocyte Chemoattractant Proteins / Q000097:blood
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; C099677:CCL13 protein, human; C106230:CCL17 protein, human; D054414:Chemokine CCL17; D018793:Interleukin-13; D018945:Monocyte Chemoattractant Proteins; D007073:Immunoglobulin E; C561806:lebrikizumab
keywords: AE; Adverse event; Asthma; FEV(1); Feno; Fraction of exhaled nitric oxide; HR; Hazard ratio; ICS; IL-13; Inhaled corticosteroid; Modified intent-to-treat; PEF; Peak expiratory flow; SABA; Short-acting β(2)-agonist; antibody; lebrikizumab; mITT; periostin; type 2 inflammation; uncontrolled