Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma
Gail M Gauvreau, Jens M Hohlfeld, Mark J FitzGerald, Louis-Philippe Boulet, Donald W Cockcroft, Beth E Davis, Stephanie Korn, Oliver Kornmann, Richard Leigh, Irvin Mayers, Henrik Watz, Sarah S Grant, Monish Jain, Maciej Cabanseki, Peter E Pertel, Ieuan Jones, Jean R Lecot, Hui Cao, Paul M O'Byrne
European Respiratory Journal 2023; DOI: 10.1183/13993003.01193-2022
Abstract
Rationale Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses.
Objective We evaluated efficacy and safety of ecleralimab, a potent inhaled neutralizing antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma.
Methods This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18–60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once daily inhaled ecleralimab or placebo. Primary endpoints were to evaluate the allergen-induced change in forced expiratory volume (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3–7h) and maximum percentage fall (LAR%) on Day 84, and safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (FeNO) were secondary and exploratory endpoints.
Measurements and Main Results Twenty-eight subjects were randomised to ecleralimab (n=15) or placebo (n=13). On Day 84, ecleralimab significantly attenuated LAR AUC3–7h by 64% (p=0.008), LAR% by 48% (p=0.029) and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC0–2h (p=0.097) and EAR% (p=0.105). FeNO levels were significantly reduced from baseline throughout the study (p<0.05) except at 24 h post-allergen (Day 43 and Day 85). Overall, ecleralimab was safe and well-tolerated.
Conclusion Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation and was safe in subjects with mild atopic asthma.
