Journal Article

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

Parker, Joseph M, White, Barbara, LaForce, Craig, Miller, S David, Molfino, Nestor A, Oh, Chad K, Robbie, Gabriel J, White, Wendy I, Pearlman, David S, Le, Chenxiong

2011

Overview

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 FEV 1 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. Trial registration ClinicalTrials (NCT): NCT00507130 and ClinicalTrials (NCT): NCT00590720

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Adult / Airway management / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Asthma / Asthma - drug therapy / Asthma - physiopathology / Asthma, Exercise-Induced - drug therapy / Asthma, Exercise-Induced - physiopathology / Critical Care Medicine / Dosage and administration / Dose-Response Relationship, Drug / Double-Blind Method / Drug therapy / Drug-Related Side Effects and Adverse Reactions / Female / Humans / Injections, Subcutaneous / Intensive / Interleukin-9 / Interleukin-9 - antagonists & inhibitors / Interleukin-9 - immunology / Internal Medicine / Male / Medicine / Medicine & Public Health / Middle Aged / Monoclonal antibodies / Patient outcomes / Physiological aspects / Pneumology/Respiratory System / Pulmonology / Quality of Life / Research Article / Respiratory Function Tests / Safety and security measures / Studies / Treatment Outcome / Young Adult