Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma

Eur Respir J. 2023 Mar 9;61(3):2201193. doi: 10.1183/13993003.01193-2022. Print 2023 Mar.


Background: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising 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 end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3-7h) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (F ENO) were secondary and exploratory end-points.

Results: 28 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). F ENO 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.

Trial registration: NCT03138811.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Allergens / adverse effects
  • Asthma*
  • Bronchial Provocation Tests
  • Cross-Over Studies
  • Cytokines
  • Double-Blind Method
  • Forced Expiratory Volume
  • Humans
  • Hypersensitivity, Immediate*
  • Immunoglobulin Fragments / therapeutic use
  • Middle Aged
  • Sputum
  • Thymic Stromal Lymphopoietin
  • Young Adult


  • Allergens
  • Cytokines
  • Immunoglobulin Fragments
  • Thymic Stromal Lymphopoietin

Associated data