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: Joseph M Parker, Chad K Oh, Craig LaForce, S David Miller, David S Pearlman, Chenxiong Le, Gabriel J Robbie, Wendy I White, Barbara White, Nestor A Molfino, MEDI-528 Clinical Trials Group
• Journal: BMC pulmonary medicine (BMC Pulm Med) Vol. 11 Pg. 14 (Feb 28 2011) ISSN: 1471-2466 [Electronic] England
• PMID: 21356110 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin-9
• enokizumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Asthma (drug therapy, physiopathology)
• Asthma, Exercise-Induced (drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions
• Female
• Humans
• Injections, Subcutaneous
• Interleukin-9 (antagonists & inhibitors, immunology)
• Male
• Middle Aged
• Quality of Life
• Respiratory Function Tests
• Treatment Outcome
• Young Adult