Clinical trial NCT05653713: Effects of CSL324 in the Lung After Segmental Challenge
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Percent reduction in mean absolute neutrophil cell counts in bronchoalveolar lavage fluid (BALF) between CSL324 and placebo
timeFrame: Obtained at 24 hours after the segmental lipopolysaccharide (LPS) challenge with endotoxin in the lung
Secondary outcomes:
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: 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
timeFrame: Baseline to 24 hours after segmental LPS challenge with endotoxin in the lung
measure: Serum concentration of CSL324
timeFrame: Up to 6 days after CSL324 administration
measure: Number of subjects with antidrug antibodies (ADAs) to CSL324 in serum
timeFrame: Prior to and up to 6 days after CSL324 and placebo administration
measure: Number and percentage of subjects with treatment-emergent adverse events (TEAEs) by treatment group
timeFrame: Up to 32 days after CSL324 and placebo administration
measure: Maximum plasma concentration (Cmax)
timeFrame: Prior to and up to 6 days after CSL324 administration
measure: Time to reach Cmax (Tmax)
timeFrame: Prior to and up to 6 days after CSL324 administration
measure: Area under the plasma concentration-time curve from time 0 to 120 hours (AUC0-120h)
timeFrame: Time 0 to 120 hours after CSL324 administration
measure: Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-last)
timeFrame: Time 0 and up to 6 days after CSL324 administration
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Fraunhofer Institute for Toxicology and Experimental Medicine
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: