Bronchiectasis Respiratory
Conditions
Interventions
Participants will be randomised using a GCP-compliant Interactive Web-based Randomisation System to one of three treatment arms. Randomisation will be stratified by inhaled antibiotic use. Depending o
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 = 86 years 2. Clinical diagnosis of bronchiectasis. 3. Able to and provided informed consent. 4. Previous CT scan of the chest demonstrating bronchiectasis in 1 or more lobes 5. P. aeruginosa in sputum, bronchoalveolar lavage or another airway sample at least once in the 24 months prior to screening. 6. A sputum sample that is culture positive for P. aeruginosa sent at the screening visit and within 35 days of randomization.
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to gremubamab or any excipient of the investigational product 2. Known clinical diagnosis of cystic fibrosis 3. Immunodeficiency requiring replacement immunoglobulin. 4. Active tuberculosis or nontuberculous mycobacterial infection (currently under treatment, or requiring treatment in the opinion of the investigator). 5. Active allergic bronchopulmonary aspergillosis (receiving treatment with corticosteroids and/or antifungal medication). 6. Recent significant haemoptysis (a volume requiring clinical intervention, within the previous 4 weeks prior to screening). 7. Treatment with long-term inhaled, systemic or nebulized anti-pseudomonal antibiotics which are newly initiated within the previous 3 months prior to screening. 8. Chronic treatment with cyclical doses of inhaled or nebulized antibiotics e.g. 28 days on and 28 days off at the time of screening. 9. Receipt of antipseudomonal antibiotics for an exacerbation during the screening period. 10. Treatment with immunosuppressives within previous 6 months prior to screening. 11. Participants with a primary diagnosis of COPD associated with >10 pack years smoking history. 12. Participants with a primary diagnosis of asthma or asthma which is considered to be poorly controlled at screening. 13. Participants with FEV1 <25% predicted value at screening. 14. Glomerular filtration rate (eGFR) below 25 ml/min/1.73m² or requiring dialysis. This will be determined at screening. 15. Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. 16. Unstable co-morbidities (e.g. cardiovascular disease, active malignancy) which in the opinion of the investigator would make participation in the trial not in the participant’s best interest. 17. Pregnant or lactating females. 18. Women of child baring age or male partners of women of childbearing age and not practicing a method of acceptable birth control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy of gremubamab on P. aeruginosa bacterial burden in sputum measured by change from baseline (day 1 - day 84) in quantitative sputum cultures (colony-forming unit (CFU)) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Efficacy of gremubamab on P. aeruginosa bacterial burden in sputum measured by change from baseline to Days 7, 14, 28 and 56 in Quantitative sputum cultures 2. Persistent effects of gremubamab on P. aeruginosa bacterial burden following discontinuation of treatment measured by change from baseline to Day 168 in quantitative sputum cultures 3. Eradication defined by negative sputum cultures for P. aeruginosa at the end of treatment (Days 84 and 168) 4. Eradication of P. aeruginosa of measured by change from baseline to Days 28, 56, 84 and 168 in QOL-B, BIM questionnaire 5. Effect of gremubamab on health-related quality of life 5.1. Measured by change from baseline to Days 84 and 168 in St. George’s Respiratory Questionnaire 5.2. Measured by change from baseline to Days 28, 56, 84 and 168 in change from baseline in Quality of Life Bronchiectasis questionnaire 5.3. Measured by change from baseline to Days 28, 56, 84 and 168 in change from baseline in Bronchiectasis Impact Measure questionnaire 6. Effect of gremubamab on time to first exacerbation measured by occurrence of exacerbations (as per EMBARC definition of exacerbation). First event from visit 1 to day 84. 7. Effect of gremubamab on pulmonary function measured by change from baseline to Day 28, 56 and 84 in forced expiratory volume in 1 second (FEV1) 8. Safety of gremubamab in patients with bronchiectasis measured by frequency of adverse events and serious adverse events between groups over 168 days 9. Safety of gremubamab in patients with bronchiectasis measured by safety lab parameters between groups over 168 days 10. Pharmacokinetics of gremubamab measured by gremubumab PK parameters through 168 days post-dose | — |
Countries
England, Northern Ireland, Scotland, Spain, United Kingdom, Wales
Contacts
Public ContactGillian Martin
Outcome results
None listed