• Asthma
• Pulmonary Clinical Trials

• Pulmonary & Respiratory Medicine

AMG 157 is a human antithymic stromal lymphopoietin (TSLP) monoclonal immunoglobulin-2γ molecule that blocks the interaction between TSLP and its receptor, a process that is thought to be important in initiating allergic inflammation. Gail M. Gauvreau, PhD, McMaster University, Hamilton, Ontario, Canada, presented data from the Double-Blind, Multiple Dose Study in Subjects With Mild Atopic Asthma study [NCT01405963; Gauvreau GM et al. Am J Crit Care Med 2014] evaluating whether the AMG 157 monoclonal antibody reduced baseline airway inflammation and allergen-induced bronchoconstriction as measured by early (6-week) and late (12-week) asthmatic responses (EAR and LAR, respectively) to allergen challenge in subjects with mild allergic asthma.

Eligible patients had mild asthma and responded to an inhaled allergen challenge with EAR and LAR during screening, which determined the concentration of the allergen challenge. Subjects were randomized in a 1:1 ratio to AMG 157 (n=16) or placebo (n=15). Patients were treated on Days 1, 29, and 57 (700-mg intravenous infusion) and were given an allergen challenge on Days 42 and 84. Induced sputum was collected 1 day before and 7 and 24 hours after each allergen challenge, and methacholine airway responsiveness was measured 1 day before and 1 day after each allergen challenge.

The baseline characteristics are detailed in Table 1.

There was a trend toward improvement in the primary end point, LAR between 3 and 7 hours after the allergen challenge as measured by maximum percentage decrease in forced expiratory volume in 1 second at 6 weeks for AMG 157 compared with placebo (14.9% vs 22.5%; treatment difference, 7.65; 95% CI, −1.30 to 16.60; p=0.09) and a significant improvement at 12 weeks (11.7% vs 21.6%, p=0.02). There was a trend toward improvement in a secondary end point, EAR between 0 and 2 hours after the allergen challenge using the same measure at 6 weeks (23.3% vs 31.8%; treatment difference, 8.57; 95% CI, 0.01 to 17.13; p=0.05) and 12 weeks (22.7% vs 32.9%; treatment difference, 10.27; 95% CI, −0.46 to 21; p=0.06) for AMG 157 compared with placebo.

Exploratory analyses revealed that the increases in blood eosinophil (p=0.004) and sputum eosinophil (p=0.015) levels were less with AMG 157 compared with placebo. Also, fractional exhaled nitric oxide, a surrogate marker of inflammation, was significantly reduced with AMG 157 treatment versus placebo (p=0.002). The number of adverse events was similar between treatments (15 in the AMG 157 group and 12 in the placebo group).

Prof. Gauvreau highlighted the unexpected reductions in inflammatory markers (blood and sputum eosinophil counts and fractional exhaled nitric oxide) with AMG 157 versus placebo before the allergen challenge, suggesting that TSLP is constitutively expressed in the airway in the setting of asthma, even in the absence of allergen exposure. She suggested that the findings support a role for targeting TSLP to control both persisting airway inflammation and allergen-induced airway responses in individuals with allergic asthma.

• © 2014 MD Conference Express®