A Phase 1b, Randomized, Double-blind, Placebo-controlled Study in Healthy Volunteers to Investigate the Effects of CSL324 in the Lung After Segmental Challenge With Endotoxin

CSL Behring1 site in 1 country40 target enrollmentDecember 20, 2022

ConditionsHealthy Volunteers

InterventionsCSL324 Placebo

Overview

Phase: Phase 1
Intervention: CSL324
Conditions: Healthy Volunteers
Sponsor: CSL Behring
Enrollment: 40
Locations: 1
Primary Endpoint: Percent reduction in mean absolute neutrophil cell counts in bronchoalveolar lavage fluid (BALF) between CSL324 and placebo
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase 1b, randomized, double-blind, placebo-controlled study in healthy volunteers to investigate the antiinflammatory effect of pretreatment with CSL324 on response to a lipopolysaccharide (LPS) endotoxin challenge in a single lung segment. Saline will be instilled into a segment in the contralateral lung for the purpose of comparison.

Registry

clinicaltrials.gov

Start Date

December 20, 2022

End Date

July 21, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

CSL Behring

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female volunteer.
•Between the ages of ≥ 18 and ≤ 65 years.
•Body mass index within the range of 18 to 32 kg/m2
•Female of nonchildbearing potential or of childbearing potential and willing to use a highly effective method of contraception (in addition to male partner condom with or without spermicide)
•Nonsmoker or an ex-smoker who has stopped smoking (including e-cigarettes or vaping devices) for \> 1 year with a smoking history of \< 10 pack-years.

Exclusion Criteria

•Any clinically significant abnormalities in physical examination findings, electrocardiogram (ECG) readings, safety laboratory test results, or ANC \< 2.0 × 109 cells/L.
•History of myeloproliferative or lymphoproliferative disease.
•Current or previous history of any immunosuppressive condition.
•Currently receiving any immunosuppressive or immunomodulatory therapy, or history of undergoing such therapy.

Arms & Interventions

CSL324

Intravenous (IV) dose of CSL324

Intervention: CSL324

Placebo

IV dose of 0.9% saline

Intervention: Placebo

Outcomes

Primary Outcomes

Percent reduction in mean absolute neutrophil cell counts in bronchoalveolar lavage fluid (BALF) between CSL324 and placebo

Time Frame: Obtained at 24 hours after the segmental lipopolysaccharide (LPS) challenge with endotoxin in the lung

Secondary Outcomes

Percent reduction in the mean change in concentrations of G CSF in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-last)(Time 0 and up to 6 days after CSL324 administration)
Percent reduction in the mean change in biomarkers of neutrophil activation in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Percent reduction in the mean change in total protein in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Serum concentration of CSL324(Up to 6 days after CSL324 administration)
Number of subjects with antidrug antibodies (ADAs) to CSL324 in serum(Prior to and up to 6 days after CSL324 and placebo administration)
Area under the plasma concentration-time curve from time 0 to 120 hours (AUC0-120h)(Time 0 to 120 hours after CSL324 administration)
Percent reduction in the mean change in concentrations of surfactant protein D (SP D) in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Number and percentage of subjects with treatment-emergent adverse events (TEAEs) by treatment group(Up to 32 days after CSL324 and placebo administration)
Percent reduction in the mean change in concentrations of sRAGE in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Maximum plasma concentration (Cmax)(Prior to and up to 6 days after CSL324 administration)
Time to reach Cmax (Tmax)(Prior to and up to 6 days after CSL324 administration)
Percent reduction in the mean change in concentrations of von Willebrand factor (vWF) in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)
Percent reduction in the mean change in concentrations of VEGF A in BALF from Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung between CSL324 and placebo(Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung)