Noncystic Fibrosis Bronchiectasis (NCFB)
Conditions
Brief summary
This study is a prospective, multicenter, randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and exploratory efficacy of nebulized CSL787 after administrations of single (SAD) ascending doses in healthy subjects and multiple (MAD) ascending doses in subjects with NCFB.
Interventions
BIOLOGICALCSL787
Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
DRUGPlacebo
Normal saline (0.9% NaCl)
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female, aged ≥ 18 years at the time of providing written informed consent For Part A (SAD) Only: * Healthy and free of medical conditions that could in the opinion of the investigator affect's the subject's participation in the study or the interpretation of results. For Part B (MAD) Only: * Diagnosis of NCFB made by a respiratory physician, confirmed per CT showing bronchial wall dilatation with or without bronchial wall thickening, with a FEV1 ≥ 40% of the predicted value regarding age, height, gender, ethnicity, and FEV1 ≥ 1 L (pre-bronchodilator values) at the Screening Visit. * No antibiotic use within 1 month before the Screening Visit. * Presence of one or more of the following bacteria (H. influenzae, P. aeruginosa, M. catarrhalis, S. pneumoniae, members of Enterobacterales family or S. aureus) in the sputum culture at the Screening Visit. * Has been fully vaccinated against COVID-19 (as per country recommendations) at least 7 days prior to Day 1
Exclusion criteria
* Evidence of a clinically significant medical condition, disorder, or disease, including but not limited to any of the following: hepatic (hepatitis, cirrhosis); biliary; renal; cardiac; bronchopulmonary; vascular; hematologic; gastrointestinal; allergy; endocrine / metabolic (diabetes, thyroid disorders, adrenal disease); neurologic; psychiatric; immunodeficiency; cancer. * History of chronic respiratory disease (eg, COPD or bronchiectasis) or current asthma with regular treatment including occasional use of an inhaler for exercise induced asthma. * Current moderate-severe allergic disease (eg, allergic rhinitis) with regular treatment. * Diagnosis of cystic fibrosis, mycobacterial disease, connective tissue disease, or alpha-1 antitrypsin deficiency as underlying disease for bronchiectasis. * Oral/parenteral corticosteroid 28 days before the Screening Visit until EOS Visit. Use of long acting bronchodilators (long acting muscarinic antagonists (LAMA) and / or long acting beta2 agonists (LABA) and/or inhaled corticosteroids that have been at a stable dose for at least 3 months before the Screening Visit is permitted; inhalation with hypertonic saline solution is permitted up to and including Day -1. * Any systemic or inhaled antibiotic for acute pulmonary exacerbation within 1 month before the Screening Visit until EOS Visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality | Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients) |
| Percent of subjects with TEAEs - overall, severity and causality | Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients) |
Secondary
| Measure | Time frame |
|---|---|
| Time of maximum concentration (Tmax) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Area under the concentration-time curve from time 0 to last quantifiable time point (AUC0-last) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Apparent total clearance of the drug (CL/F) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Apparent volume of distribution during the elimination phase (V/F) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Terminal elimination half-life (T1/2) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
| Cmax of CSL787 in sputum and serum of NCFB subjects | On Day 1, after dosing |
| AR for AUCtau of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| Ctrough of CSL787 in sputum and serum of NCFB subjects | On Day 1, after dosing |
| AUCtau of CSL787 in sputum and serum of NCFB subjects | On Day 1, after dosing |
| T1/2 of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| CL/F of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| V/F of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| Accumulation Ratio (AR) for Cmax of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| AR for Ctrough of CSL787 in sputum and serum of NCFB subjects | On Day 14, after last dose |
| Tmax of CSL787 in sputum and serum of NCFB subjects | On Day 1, after dosing |
| Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects | Up to 8 days from inhalation |
Countries
Germany, United Kingdom
Outcome results
None listed