Bronchiectasis is a chronic respiratory disease characterised by cough, sputum production and recurrent respiratory infections. Impairment of mucociliary clearance leads to increased susceptibility to lung infections and progressive decline in respiratory function. 

Approximately 1/3 of patients become chronically infected with the antibiotic resistant pathogen Pseudomonas aeruginosa (P. aeruginosa). This pathogen evades killing by immune cells and forms biofilms resulting in infections that persist despite treatment with antibiotics. P. aeruginosa infection is associated with a 7 fold increased risk of hospitalization and a 3 fold increased risk of mortality in bronchiectasis.

Current treatment options for P. aeruginosa are inadequate. Patients have ongoing frequent exacerbations and poor quality of life despite the availability of inhaled antibiotics, which are widely used “off label” and macrolides. The most recent meta-analysis of inhaled antibiotic use in bronchiectasis found that on average they reduced bacterial load (primarily of P. aeruginosa) by 2 log units and reduced exacerbations by up to 20%. The widespread use of prophylactic antibiotics carries a significant risk of antibiotic resistance. Antibiotic treatments are not specific to respiratory pathogens and may therefore reduce the overall diversity of the airway microbiome. Low microbiome diversity is associated with increased mortality in bronchiectasis. There is an urgent need for novel antipseudomonal treatments and particularly pathogen specific approaches.

This protocol describes a Proof of Principle randomized trial of Gremubamab in patients with bronchiectasis (not due to cystic fibrosis). The objective of the study will be to establish the antipseudomonal activity in vivo, investigating two doses, pharmacokinetics (PK) profile and the preliminary clinical efficacy, using the endpoints of exacerbations and quality of life, of Gremubamab in patients with bronchiectasis who are chronically infected with P. aeruginosa. This is an investigator initiated research study proposed by the EMBARC consortium, an international network of investigators in the field of bronchiectasis.

The objective of the GREAT-2 trial will be to establish the antipseudomonal activity in-vivo, the optimal dosing and the preliminary clinical efficacy (exacerbations and quality of life) of Gremubamab in patients with bronchiectasis who are chronically infected with P. aeruginosa.

Participants will be identified, recruited and complete the research activities in approximately 30 Secondary care settings across the UK and Spain.