Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function

• Status: Not yet recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Double-blind, randomized, cross-over trial involving 20 participants with bronchiectasis.

This trial will make an important contribution to therapeutic development in bronchiectasis by determining whether alpha-1 antitrypsin (AAT) therapy results in reduced airway inflammation and improves neutrophil function.

Patients will be randomly assigned to receive Prolastin-C 120mg/kg (n=10 patients) by weekly intravenous infusions, Prolastin-C 180mg/kg (n=10 patients) by weekly intravenous infusions or placebo (0.9% saline) for a period of 4 weeks, followed by a 3-5 week washout period and a further 4 weeks during which patients will cross-over to receive the alternative therapy.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Treatments: Alpha 1-Antitrypsin; Protease Inhibitors

Criteria

Inclusion Criteria:

• Age >18 years

• Bronchiectasis on high resolution computerised tomography (CT) scan affecting 1 or more lobes

• Sputum neutrophil elastase activity greater than or equal to 7 µg/ml on neutrophil elastase assay at the screening visit*

• Daily sputum production as determined by the researcher from the patient's self-report

• Able to provide a sputum sample at the screening and randomization visits either spontaneously

• Ability to give informed consent

• Able to perform all trial procedures with minimal assistance

• Willing to have pregnancy testing, if appropriate

Exclusion Criteria:

• Severe alpha-1 antitrypsin deficiency (<57 mg/dl in serum) regardless of genotype#

• Immunoglobulin A (IgA) deficient patients with antibodies against IgA

• History of anaphylaxis or other severe systemic reaction to Alpha1-Proteinase Inhibitor

• Primary diagnosis of Chronic Obstructive Pulmonary Disease (COPD) in the opinion of the investigator

• Primary Diagnosis of asthma in the opinion of the investigator

• Active allergic bronchopulmonary aspergillosis, NTM, immunodeficiency or another aetiology of bronchiectasis requiring a specific treatment

• Treatment with antibiotic therapy for an exacerbation of bronchiectasis (other than long term oral or inhaled antibiotics at stable dose) in the 4 weeks prior to randomization

• Cystic fibrosis

• Unstable cardiac disease in the opinion of the investigator

• Congestive cardiac failure and in the opinion of the investigator should not receive iv infusions.

• Traction bronchiectasis due to interstitial lung disease

• Current smoker

• Pregnant or breast feeding