Back to resultsStudy to Assess CSL787 in Non-cystic Fibrosis Bronchiectasis (NCFB)
Primary Purpose
Noncystic Fibrosis Bronchiectasis (NCFB)
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CSL787
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Noncystic Fibrosis Bronchiectasis (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.
Sites / Locations
- IKF Pneumologie Institute
- Medicines Evaluation Unit (MEU)
- Celerion
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
CSL787 (SAD dose 1)
CSL787 (SAD dose 2)
CSL787 (SAD dose 3)
CSL787 (SAD dose 4)
CSL787 (MAD dose 1)
CSL787 (MAD dose 2)
CSL787 (MAD dose 3)
Placebo
Arm Description
Inhalation by mouth of a nebulized aerosol in healthy subjects
Inhalation by mouth of a nebulized aerosol in healthy subjects
Inhalation by mouth of a nebulized aerosol in healthy subjects
Inhalation by mouth of a nebulized aerosol in healthy subjects
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Inhalation by mouth of a nebulized aerosol
Outcomes
Primary Outcome Measures
Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality
Percent of subjects with TEAEs - overall, severity and causality
Secondary Outcome Measures
Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects
Time of maximum concentration (Tmax) of CSL787 in sputum and serum in healthy subjects
Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) of CSL787 in sputum and serum in healthy subjects
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
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of CSL787 in sputum and serum in healthy subjects
Apparent total clearance of the drug (CL/F) of CSL787 in sputum and serum in healthy subjects
Apparent volume of distribution during the elimination phase (V/F) of CSL787 in sputum and serum in healthy subjects
Terminal elimination half-life (T1/2) of CSL787 in sputum and serum in healthy subjects
Cmax of CSL787 in sputum and serum of NCFB subjects
Tmax of CSL787 in sputum and serum of NCFB subjects
Ctrough of CSL787 in sputum and serum of NCFB subjects
AUCtau of CSL787 in sputum and serum of NCFB subjects
Cmax of CSL787 in sputum and serum of NCFB subjects
Tmax of CSL787 in sputum and serum of NCFB subjects
Ctrough of CSL787 in sputum and serum of NCFB subjects
AUCtau of CSL787 in sputum and serum of NCFB subjects
T1/2 of CSL787 in sputum and serum of NCFB subjects
CL/F of CSL787 in sputum and serum of NCFB subjects
V/F of CSL787 in sputum and serum of NCFB subjects
Accumulation Ratio (AR) for Cmax of CSL787 in sputum and serum of NCFB subjects
AR for Ctrough of CSL787 in sputum and serum of NCFB subjects
AR for AUCtau of CSL787 in sputum and serum of NCFB subjects
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04643587
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
December 7, 2020 (Actual)
Primary Completion Date
March 20, 2023 (Actual)
Study Completion Date
March 20, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Noncystic Fibrosis Bronchiectasis (NCFB)
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL787 (SAD dose 1)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in healthy subjects
Arm Title
CSL787 (SAD dose 2)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in healthy subjects
Arm Title
CSL787 (SAD dose 3)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in healthy subjects
Arm Title
CSL787 (SAD dose 4)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in healthy subjects
Arm Title
CSL787 (MAD dose 1)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Arm Title
CSL787 (MAD dose 2)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Arm Title
CSL787 (MAD dose 3)
Arm Type
Experimental
Arm Description
Inhalation by mouth of a nebulized aerosol in NCFB subjects
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Inhalation by mouth of a nebulized aerosol
Intervention Type
Biological
Intervention Name(s)
CSL787
Intervention Description
Human plasma-derived polyvalent immunoglobulin G (IgG) administered via inhalation of an aerosol produced using a nebulizer
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline (0.9% NaCl)
Primary Outcome Measure Information:
Title
Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality
Time Frame
Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
Title
Percent of subjects with TEAEs - overall, severity and causality
Time Frame
Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
Secondary Outcome Measure Information:
Title
Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Time of maximum concentration (Tmax) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
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
Time Frame
Up to 8 days from inhalation
Title
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Apparent total clearance of the drug (CL/F) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Apparent volume of distribution during the elimination phase (V/F) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Terminal elimination half-life (T1/2) of CSL787 in sputum and serum in healthy subjects
Time Frame
Up to 8 days from inhalation
Title
Cmax of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 1, after dosing
Title
Tmax of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 1, after dosing
Title
Ctrough of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 1, after dosing
Title
AUCtau of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 1, after dosing
Title
Cmax of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
Tmax of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
Ctrough of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
AUCtau of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
T1/2 of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
CL/F of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
V/F of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
Accumulation Ratio (AR) for Cmax of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
AR for Ctrough of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
Title
AR for AUCtau of CSL787 in sputum and serum of NCFB subjects
Time Frame
On Day 14, after last dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
IKF Pneumologie Institute
City
Frankfurt
Country
Germany
Facility Name
Medicines Evaluation Unit (MEU)
City
Manchester
State/Province
England
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
Facility Name
Celerion
City
Belfast
State/Province
Northern Ireland
ZIP/Postal Code
BT9 6AD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Study to Assess CSL787 in Non-cystic Fibrosis Bronchiectasis (NCFB)
We'll reach out to this number within 24 hrs