Effects of CSL324 in the Lung After Segmental Challenge

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05653713
• Other study ID #: CSL324_1004
• Secondary ID: 2022-002404-20
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2022
• Est. completion date: July 21, 2023

Study information

• Verified date: November 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 21, 2023
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• CSL324
Single intravenous (IV) dose of CSL324
• Placebo
IV dose of 0.9% saline

Locations

Country	Name	City	State
Germany	Fraunhofer Institute for Toxicology and Experimental Medicine	Hannover

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Biomarkers are (neutrophil elastase [NE], alpha [a] 1 antitrypsin [AAT) complex, and myeloperoxidase [MPO]) in BALF	Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum concentration of CSL324		Up to 6 days after CSL324 administration
Secondary	Number of subjects with antidrug antibodies (ADAs) to CSL324 in serum		Prior to and up to 6 days after CSL324 and placebo administration
Secondary	Number and percentage of subjects with treatment-emergent adverse events (TEAEs) by treatment group		Up to 32 days after CSL324 and placebo administration
Secondary	Maximum plasma concentration (Cmax)		Prior to and up to 6 days after CSL324 administration
Secondary	Time to reach Cmax (Tmax)		Prior to and up to 6 days after CSL324 administration
Secondary	Area under the plasma concentration-time curve from time 0 to 120 hours (AUC0-120h)		Time 0 to 120 hours after CSL324 administration
Secondary	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