Effects of CSL324 in the Lung After Segmental Challenge

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: CSL324; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Fraunhofer Institute for Toxicology and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Actual): July 21, 2023
• Study Completion (Actual): July 21, 2023

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: CSL324_1004; 2022-002404-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No