Efficacy and Safety of AMG 317, an IL-4Ra Antagonist, in Atopic Asthmatic Subjects: A Randomized, Double-blind, Placebo-controlled Study

RATIONALE: To evaluate the efficacy and safety of AMG 317 (a monoclonal antibody that inhibits both IL-4 and IL-13 signaling) in subjects with moderate to severe atopic asthma.METHODS: This 12-week randomized, double-blind, placebo-controlled study included subjects with uncontrolled asthma: Asthma Control Questionnaire (ACQ) $1.5 and FEV1 50-80%. Subjects were randomized to 12 weekly injections of AMG 317 (75mg, 150mg, 300mg) or placebo. The primary endpoint was improvement in ACQ score.RESULTS: This interim analysis included 260 subjects. At week 12, mean improvements in ACQ scores were: placebo (0.48), AMG 317 75mg (0.33), 150mg (0.56), and 300mg (0.65) (p=NS for all) (minimum important difference=0.5). Median improvement in total serum IgE was significantly greater in the 300mg AMG 317 group vs placebo (39.0 vs 1.0 IU/mL, P<0.05). Exploratory analyses of the top tertile of the most symptomatic subjects (baseline ACQ>2.86) showed a difference in mean ACQ improvement of 0.47 in the 300mg AMG 317 group vs placebo (1.2 vs 0.73, P=0.12) and an improvement in FEV1 and AM peak flow of 0.266 vs -0.080L (P<0.05) and 18.6 vs -6.8L/min (P=0.17), respectively. Rescue beta-agonist use in the 300mg AMG 317 group vs placebo was 1.65 vs 0.32 puffs/day, (P=0.34). No AMG 317 treatment-related SAEs were reported.CONCLUSIONS: This study demonstrated small differences in ACQ improvement between AMG 317 and placebo and an overall trend in dose response. However, in the most symptomatic subjects, clinically meaningful differences were observed between 300mg AMG 317 and placebo. AMG 317 was safe and well-tolerated. RATIONALE: To evaluate the efficacy and safety of AMG 317 (a monoclonal antibody that inhibits both IL-4 and IL-13 signaling) in subjects with moderate to severe atopic asthma. METHODS: This 12-week randomized, double-blind, placebo-controlled study included subjects with uncontrolled asthma: Asthma Control Questionnaire (ACQ) $1.5 and FEV1 50-80%. Subjects were randomized to 12 weekly injections of AMG 317 (75mg, 150mg, 300mg) or placebo. The primary endpoint was improvement in ACQ score. RESULTS: This interim analysis included 260 subjects. At week 12, mean improvements in ACQ scores were: placebo (0.48), AMG 317 75mg (0.33), 150mg (0.56), and 300mg (0.65) (p=NS for all) (minimum important difference=0.5). Median improvement in total serum IgE was significantly greater in the 300mg AMG 317 group vs placebo (39.0 vs 1.0 IU/mL, P<0.05). Exploratory analyses of the top tertile of the most symptomatic subjects (baseline ACQ>2.86) showed a difference in mean ACQ improvement of 0.47 in the 300mg AMG 317 group vs placebo (1.2 vs 0.73, P=0.12) and an improvement in FEV1 and AM peak flow of 0.266 vs -0.080L (P<0.05) and 18.6 vs -6.8L/min (P=0.17), respectively. Rescue beta-agonist use in the 300mg AMG 317 group vs placebo was 1.65 vs 0.32 puffs/day, (P=0.34). No AMG 317 treatment-related SAEs were reported. CONCLUSIONS: This study demonstrated small differences in ACQ improvement between AMG 317 and placebo and an overall trend in dose response. However, in the most symptomatic subjects, clinically meaningful differences were observed between 300mg AMG 317 and placebo. AMG 317 was safe and well-tolerated.