title: Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma.
abstract: BACKGROUND
  Interleukin-9 (IL-9)-targeted therapies may offer a novel approach for treating asthmatics. Two randomized placebo-controlled studies were conducted to assess the safety profile and potential efficacy of multiple subcutaneous doses of MEDI-528, a humanized anti-IL-9 monoclonal antibody, in asthmatics.
  
  
  METHODS
  Study 1: adults (18-65 years) with mild asthma received MEDI-528 (0.3, 1, 3 mg/kg) or placebo subcutaneously twice weekly for 4 weeks. Study 2: adults (18-50 years) with stable, mild to moderate asthma and exercise-induced bronchoconstriction received 50 mg MEDI-528 or placebo subcutaneously twice weekly for 4 weeks. Adverse events (AEs), pharmacokinetics (PK), immunogenicity, asthma control (including asthma exacerbations), and exercise challenge test were evaluated in study 1, study 2, or both.
  
  
  RESULTS
  In study 1 (N = 36), MEDI-528 showed linear serum PK; no anti-MEDI-528 antibodies were detected. Asthma control: 1/27 MEDI-528-treated subjects had 1 asthma exacerbation, and 2/9 placebo-treated subjects had a total of 4 asthma exacerbations (one considered a serious AE). In study 2, MEDI-528 (n = 7) elicited a trend in the reduction in mean maximum decrease in FEV1 post-exercise compared to placebo (n = 2) (-6.49% MEDI-528 vs -12.60% placebo; -1.40% vs -20.10%; -5.04% vs -15.20% at study days 28, 56, and 150, respectively). Study 2 was halted prematurely due to a serious AE in an asymptomatic MEDI-528-treated subject who had an abnormal brain magnetic resonance imaging that was found to be an artifact on further evaluation.
  
  
  CONCLUSIONS
  In these studies, MEDI-528 showed an acceptable safety profile and findings suggestive of clinical activity that support continued study in subjects with mild to moderate asthma.
authors.affiliation: MedImmune LLC, Gaithersburg, MD, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Parker
authors.forename: Chad K
authors.initials: CK
authors.lastname: Oh
authors.forename: Craig
authors.initials: C
authors.lastname: LaForce
authors.forename: S David
authors.initials: SD
authors.lastname: Miller
authors.forename: David S
authors.initials: DS
authors.lastname: Pearlman
authors.forename: Chenxiong
authors.initials: C
authors.lastname: Le
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Robbie
authors.forename: Wendy I
authors.initials: WI
authors.lastname: White
authors.forename: Barbara
authors.initials: B
authors.lastname: White
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001250:Asthma, Exercise-Induced / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016906:Interleukin-9; C542276:enokizumab