PURPOSE:Interleukin-9 (IL-9) increases airway inflammation, obstruction and hyperresponsiveness, mucin production, mast cell generation, and Th2 lymphocyte and eosinophil accumulation in experimental systems. Conversely, blocking IL-9 reduces airway inflammation and hyperresponsiveness in animal models of asthma. Thus, blocking IL-9 may provide benefit in asthma. MEDI-528, a humanized, IL-9 monoclonal antibody, is currently in development by MedImmune, LLC as a potential therapy for asthma. Single ascending subcutaneous doses of MEDI-528, up to 9 mg/kg, have shown no serious adverse effects in healthy volunteers. The current report summarizes the first clinical experience with multiple subcutaneous doses in asthmatics.
METHODS:MI-CP-131 is Phase 2a, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety and tolerability of multiple SC doses of MEDI-528, ranging from 0.3, 1.0, and 3.0 mg/kg, in patients with mild to moderate atopic asthma. Patients received 8 total doses over a two week period and were followed for a total of 150 days. This report summarizes the blinded safety information from the first two cohorts (0.3 and 1.0 mg/kg, 12 patients each) in the study.
RESULTS:No serious adverse events (SAEs) have been reported. There have been no reports of deaths, interruptions of study drug administration, discontinuations due to adverse events (AEs), or anaphylaxis. The three most common AEs were nasopharyngitis, urinary tract infection, and blood in the urine. All AEs were mild to moderate, and all resolved without sequelae. No clinically significant trends in laboratory values were observed, and all abnormalities were mild or moderate in severity.
CONCLUSION:Multiple subcutaneous doses of either 0.3 mg/kg or 1.0 mg/kg of MEDI -528 appear to be well tolerated in patients with mild to moderate atopic asthma.
CLINICAL IMPLICATIONS:MEDI-528 merits continued evaluation as a potential therapy for asthma.
DISCLOSURE:Joseph Parker, Employee Joseph Parker, Nestor Molfino, Barbara White, and Suha Suri are employees of MedImmune LLC.; Consultant fee, speaker bureau, advisory committee, etc. Craig LaForce, Louis-Phillippe Boulet, David Pearlman, Charles Fogarty, S. David Miller, Gail Gauvreau, Kieran Killian, Howard Kaiser, and Catherine Lemiere are investigators in a MedImmune sponsored clinical trial. Gail Gauvreau is a consultant to MedImmune.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. MEDI-528 is an investigational product for the treatment of asthma.