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

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

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Article number14
JournalBMC Pulmonary Medicine
Volume11
DOIs
StatePublished - Feb 28 2011
Externally publishedYes

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Interleukin-9
Asthma
Monoclonal Antibodies
Safety
Placebos
Pharmacokinetics
MEDI-528
Exercise-Induced Asthma
Bronchoconstriction
Exercise Test
Artifacts
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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

In: BMC Pulmonary Medicine, Vol. 11, 14, 28.02.2011.

Research output: Contribution to journalArticle

Parker, Joseph M. ; Oh, Chad K. ; LaForce, Craig ; Miller, S. David ; Pearlman, David S. ; Le, Chenxiong ; Robbie, Gabriel J. ; White, Wendy I. ; White, Barbara ; Molfino, Nestor A. / 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. In: BMC Pulmonary Medicine. 2011 ; Vol. 11.
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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. Trial registration: ClinicalTrials (NCT): NCT00507130 and ClinicalTrials (NCT): NCT00590720.",
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AU - Oh, Chad K.

AU - LaForce, Craig

AU - Miller, S. David

AU - Pearlman, David S.

AU - Le, Chenxiong

AU - Robbie, Gabriel J.

AU - White, Wendy I.

AU - White, Barbara

AU - Molfino, Nestor A.

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