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

BMC Pulmonary Medicine

Research Article

David S Pearlman¹  Gabriel J Robbie²  Wendy I White²  Joseph M Parker²  Chad K Oh²  Chenxiong Le²  Nestor A Molfino²  Barbara White³  Craig LaForce⁴  S David Miller⁵ 

[1] Colorado Allergy & Asthma Centers PC, Denver, CO, USA;MedImmune, LLC, Gaithersburg, MD, USA;MedImmune, LLC, Gaithersburg, MD, USA;Current address: UCB Biosciences, Inc, Raleigh, NC, USA;North Carolina Clinical Research, Raleigh, NC, USA;Northeast Medical Research Associates, North Dartmouth, MA, USA;

关键词: Asthma;    Asthma Exacerbation;    Omalizumab;    Nedocromil;    Nedocromil Sodium;   

DOI  :  10.1186/1471-2466-11-14

 received in 2010-06-08, accepted in 2011-02-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundInterleukin-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.MethodsStudy 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.ResultsIn 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.ConclusionsIn 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.Trial registrationClinicalTrials (NCT): NCT00507130 and ClinicalTrials (NCT): NCT00590720

【 授权许可】

Unknown   
© Parker et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.