Study to Assess CSL787 in Non-cystic Fibrosis Bronchiectasis (NCFB)

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)

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.

Study Overview

• Status: Completed
• Conditions: Noncystic Fibrosis Bronchiectasis (NCFB)
• Intervention / Treatment: Biological: CSL787; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Frankfurt, Germany
    • IKF Pneumologie Institute
• United Kingdom
  • England
    • Manchester, England, United Kingdom, M23 9QZ
      • Medicines Evaluation Unit (MEU)
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 6AD
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL787 (SAD dose 1); Inhalation by mouth of a nebulized aerosol in healthy subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (SAD dose 2); Inhalation by mouth of a nebulized aerosol in healthy subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (SAD dose 3); Inhalation by mouth of a nebulized aerosol in healthy subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (SAD dose 4); Inhalation by mouth of a nebulized aerosol in healthy subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (MAD dose 1); Inhalation by mouth of a nebulized aerosol in NCFB subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (MAD dose 2); Inhalation by mouth of a nebulized aerosol in NCFB subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Experimental: CSL787 (MAD dose 3); Inhalation by mouth of a nebulized aerosol in NCFB subjects	Biological: CSL787; Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Placebo Comparator: Placebo; Inhalation by mouth of a nebulized aerosol	Drug: Placebo; Normal saline (0.9% NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects	Up to 8 days from inhalation
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
Tmax of CSL787 in sputum and serum of NCFB subjects	On Day 1, after dosing
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
Cmax 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 14, after last dose
Ctrough of CSL787 in sputum and serum of NCFB subjects	On Day 14, after last dose
AUCtau of CSL787 in sputum and serum of NCFB subjects	On Day 14, after last dose
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
AR for AUCtau of CSL787 in sputum and serum of NCFB subjects	On Day 14, after last dose

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): March 12, 2023
• Study Completion (Actual): March 12, 2023

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis
• Other Study ID Numbers: CSL787_1001; 2020-002684-66 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No