A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma
Edward Piper,Christopher E. Brightling,Robert Niven,Chad K. Oh,Raffaella Faggioni,Kwai Poon,Dewei She,Chris Kell,Richard D. May,Gregory P. Geba,Nestor A. Molfino +10 more
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TLDR
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 was assessed, although no improvement in ACQ-6 was observed, although tralokerumab treatment was associated with improved lung function.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 β2-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 (FEV1) 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. β2-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 FEV1 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.read more
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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
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IL-4 and IL-13 signaling in allergic airway disease.
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References
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Interleukin-13: Central Mediator of Allergic Asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TL;DR: In this paper, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal Article
Interleukin-13: Central mediator of allergic asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TL;DR: In this article, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal ArticleDOI
Development and validation of a questionnaire to measure asthma control
TL;DR: The Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.
Journal ArticleDOI
Requirement for IL-13 Independently of IL-4 in Experimental Asthma
Gabriele Grünig,Martha L. Warnock,Adil E. Wakil,Rajeev Venkayya,Frank Brombacher,Donna M. Rennick,Dean Sheppard,Markus Mohrs,Debra D. Donaldson,Richard M. Locksley,David B. Corry +10 more
TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
Journal ArticleDOI
Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production
Zhou Zhu,Robert J. Homer,Robert J. Homer,Zhonde Wang,Qingsheng Chen,Gregory P. Geba,Gregory P. Geba,Jingming Wang,Yong Zhang,Jack A. Elias +9 more
TL;DR: The targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR in transgene-positive animals.