Effects of CSL324 in the Lung After Segmental Challenge

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: CSL324
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL324<br>Intravenous (IV) dose of CSL324 | Drug: CSL324<br>* Single intravenous (IV) dose of CSL324<br>* Other names: Recombinant anti-granulocyte colony-stimulating factor (G-CSF) receptor monoclonal antibody (mAb);|
| Placebo Comparator: Placebo<br>IV dose of 0.9% saline | Drug: Placebo<br>* IV dose of 0.9% saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 [α] 1 antitrypsin [AAT) complex, and myeloperoxidase [MPO]) in BALF | 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 | 
| 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 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Number and percentage of subjects with treatment-emergent adverse events (TEAEs) by treatment group |  | Up to 32 days after CSL324 and placebo administration | 
| 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 | 
| Area under the plasma concentration-time curve from time 0 to 120 hours (AUC0-120h) |  | Time 0 to 120 hours after CSL324 administration | 
| 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 |