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CORDIS

FLAGELLIN AEROSOL THERAPY AS AN IMMUNOMODULATORY ADJUNCT TO THE ANTIBIOTIC TREATMENT OF DRUG-RESISTANT BACTERIAL PNEUMONIA

Project description

Flagellin aerosol therapy in treatment of drug-resistant bacterial pneumonia

Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Standard care with antibiotics is often complicated by antimicrobial resistance (AMR), resulting in curative failure. The EU-funded FAIR project aims to assess an adjunct to antibiotic therapy as an emerging concept to overcome AMR in pneumonia. The research focuses on the unique immunomodulator flagellin that enhances airway epithelial innate immune defences, and the development of airway-specific aerosol delivery by nebulisation. FAIR's main objectives include optimisation of nebulisation and demonstration of flagellin-associated enhancement of the antibiotic response, as well as obtaining pharmacokinetics and pharmacodynamics models for clinical validation and assessing flagellin nebulisation safety in a Phase I clinical trial.

Objective

Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Antibiotics constitute the standard of care but are faced with the emergence of antimicrobial resistance (AMR) and the curative failure. The FAIR consortium aims at assessing an adjunct to antibiotic therapy as an emerging concept of overcome AMR in pneumonia. The project leverages (i) a unique immunomodulatory flagellin that enhances airway epithelial innate immune defences and increases the therapeutic outcome relative to antibiotic alone, and (ii) airway-specific aerosol delivery by nebulization.

FAIR’s objectives are to:
• develop nebulization modalities for optimal airway targeting and rapid action at the infection site
• demonstrate that nebulized flagellin strengthens the response to antibiotics in relevant preclinical models of antibiotic-resistant pneumonia
• identify host immune factors required for the gain of protection with systems biology
• implement pharmacokinetics/pharmacodynamics model-based design and simulation for clinical validation
• assess nebulized flagellin’s safety in a Phase I clinical trial.
• analyze the acceptability and economic relevance of the therapy
• identify stratification markers that predict the course of pneumonia and treatment in antibiotic-treated cohorts.

Expected outcomes include the enrichment of the pipeline of novel treatments against pneumonia, reinforcement of EU capacity to control AMR and infections, the Phase I safety report on nebulized flagellin, recommendations for future trials, and acceptability by the stakeholders and cost-effectiveness for public health. FAIR will develop new avenues of research on mechanisms of action of the adjunct flagellin, and will define (for future trials) the subpopulation of patients that might benefit most from this treatment. Our industrial partnerships and exploitation plan will enable straightforward development of drug and nebuliser device, and bring innovation to the patients.

Call for proposal

H2020-SC1-BHC-2018-2020

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Sub call

H2020-SC1-2019-Two-Stage-RTD

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 2 082 152,95
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 3 156 349,54

Participants (14)