Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function

NCT05582798 | Completed Phase 4 FDA Drug

• 1 other identifier: 1.002.21
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bronchiectasis Adult

Outcome Measures

Primary Outcomes (1)

• To determine the effect of intravenous alpha-1 proteinase inhibitor on sputum neutrophil elastase activity

  Change from baseline in sputum neutrophil elastase activity measured in units/ml

  Baseline and 4 weeks

Secondary Outcomes (13)

• To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function

  Baseline and 4 weeks

• To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function

  Baseline and 4 weeks

• To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function

  Baseline and 4 weeks

• To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function

  Baseline and 4 weeks

• To determine the effect of intravenous alpha-1 proteinase inhibitor on neutrophil function

  Baseline and 4 weeks

Study Arms (4)

Alpha1-Proteinase Inhibitor 180mg/kg

ACTIVE COMPARATOR

Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml

Drug: Alpha 1-Proteinase Inhibitor 180mg/kg

Alpha1-Proteinase Inhibitor 120mg/kg

ACTIVE COMPARATOR

Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion, 50mg/ml

Drug: Alpha 1-Proteinase Inhibitor 120mg/kg

Placebo 1

PLACEBO COMPARATOR

Sodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 180mg/kg, intravenous infusion.

Drug: Sodium chloride

Placebo 2

PLACEBO COMPARATOR

Sodium chloride 0.9% volume to match that of Alpha1-Proteinase Inhibitor 120mg/kg, intravenous infusion.

Drug: Sodium chloride

Interventions

Alpha 1-Proteinase Inhibitor 180mg/kg DRUG

alpha1-proteinase inhibitor (human) intravenous infusion

Also known as: Prolastin-C Liquid

Alpha1-Proteinase Inhibitor 180mg/kg

Alpha 1-Proteinase Inhibitor 120mg/kg DRUG

alpha1-proteinase inhibitor (human) intravenous infusion

Also known as: Prolastin-C Liquid

Alpha1-Proteinase Inhibitor 120mg/kg

Sodium chloride DRUG

Sodium chloride 09.% intravenous infusion

Placebo 1; Placebo 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

NHS Tayside

Dundee, United Kingdom

Location

MeSH Terms

Interventions

alpha 1-Antitrypsin; Sodium Chloride

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• James Chalmers

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 29, 2022
• First Posted: October 17, 2022
• Study Start: November 1, 2022
• Primary Completion: August 12, 2024
• Study Completion: August 12, 2024
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)