title: A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma.
abstract: Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β(2)-agonist use and safety. Numerical end-points are reported as mean±sd. At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumab versus -0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV(1)) were 0.21±0.38 L versus 0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β(2)-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45 versus placebo -0.10±1.49 (p=0.020). The increase in FEV(1) following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab. No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.
authors: Clinical Development, MedImmune Ltd., Granta Park, Cambridge, UK. pipered@medimmune.com
authors: Edward
authors: E
authors: Piper
authors: Christopher
authors: C
authors: Brightling
authors: Robert
authors: R
authors: Niven
authors: Chad
authors: C
authors: Oh
authors: Raffaella
authors: R
authors: Faggioni
authors: Kwai
authors: K
authors: Poon
authors: Dewei
authors: D
authors: She
authors: Chris
authors: C
authors: Kell
authors: Richard D
authors: RD
authors: May
authors: Gregory P
authors: GP
authors: Geba
authors: Nestor A
authors: NA
authors: Molfino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D018793:Interleukin-13 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018793:Interleukin-13; C574065:tralokinumab