Effects of CSL324 in the Lung After Segmental Challenge

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: CSL324; Drug: Placebo

• Registration Number: NCT05653713
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-08
• Study First Submitted QC: 2022-12-15
• Study First Posted: 2022-12-16
• Study Start: 2022-12-20
• Primary Completion: 2023-07-21
• Study Completion: 2023-07-21
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSL324	CSL324	Intravenous (IV) dose of CSL324
Placebo	Placebo	IV dose of 0.9% saline

Primary Outcome Measures

Name	Time	Method
Percent reduction in mean absolute neutrophil cell counts in bronchoalveolar lavage fluid (BALF) between CSL324 and placebo	Obtained at 24 hours after the segmental lipopolysaccharide (LPS) challenge with endotoxin in the lung

Secondary Outcome Measures

Name	Time	Method
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	Biomarkers are (neutrophil elastase \[NE\], alpha \[α\] 1 antitrypsin \[AAT) complex, and myeloperoxidase \[MPO\]) in BALF
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

Trial Locations

Locations (1)

Fraunhofer Institute for Toxicology and Experimental Medicine; 🇩🇪 Hannover, Germany