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 (FEV(1)) during the late asthmatic response (LAR) measured by area under the curve (AUC(3-7h)) 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 AUC(3-7h) 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 AUC(0-2h) (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.
- Gauvreau, G. M.
- Hohlfeld, J. M.
- FitzGerald, M. J.
- Boulet, L. P.
- Cockcroft, D. W.
- Davis, B. E.
- Korn, S.
- Kornmann, O.
- Leigh, R.
- Mayers, I.
- Watz, H.
- Grant, S. S.
- Jain, M.
- Cabanseki, M.
- Pertel, P. E.
- Jones, I.
- Lecot, J. R.
- Cao, H.
- O'Byrne, P. M.
