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.
Author(s): Parker JM, Oh CK, LaForce C, Miller SD, Pearlman DS, Le C, Robbie GJ, White WI,
White B, Molfino NA; MEDI-528 Clinical Trials Group.
Collaborators: Boulet LP, Fogarty C, Gauvreau G, Kaiser H, Lemiere C, Brazinsky
S, Nayak A, Korenblat P.
Affiliation(s): MedImmune LLC, Gaithersburg, MD, USA.
Publication date & source: 2011, BMC Pulm Med. , 11:14
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.
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