Clinical trial NCT04643587: Study to Assess CSL787 in Non-cystic Fibrosis Bronchiectasis (NCFB)
Official title: A Phase 1, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of Nebulized CSL787 in Healthy Subjects and Subjects With Non-Cystic Fibrosis Bronchiectasis (NCFB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Noncystic Fibrosis Bronchiectasis (NCFB)
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality
timeFrame: Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
measure: Percent of subjects with TEAEs - overall, severity and causality
timeFrame: Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
Secondary outcomes:
measure: Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Time of maximum concentration (Tmax) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: 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
timeFrame: Up to 8 days from inhalation
measure: Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Apparent total clearance of the drug (CL/F) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Apparent volume of distribution during the elimination phase (V/F) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Terminal elimination half-life (T1/2) of CSL787 in sputum and serum in healthy subjects
timeFrame: Up to 8 days from inhalation
measure: Cmax of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 1, after dosing
measure: Tmax of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 1, after dosing
measure: Ctrough of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 1, after dosing
measure: AUCtau of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 1, after dosing
measure: Cmax of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: Tmax of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: Ctrough of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: AUCtau of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: T1/2 of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: CL/F of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: V/F of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: Accumulation Ratio (AR) for Cmax of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: AR for Ctrough of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
measure: AR for AUCtau of CSL787 in sputum and serum of NCFB subjects
timeFrame: On Day 14, after last dose
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: IKF Pneumologie Institute
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit (MEU)
state: England
city: Belfast
country: United Kingdom
facility: Celerion
state: Northern Ireland
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: