A Clinical Study to Test the Safety, Exposure, and Pharmacodynamic Markers of CSL311 in Patients With Mild-to-moderate Asthma and in Healthy Volunteers

Phase 1

Completed

• Conditions: Asthma
• Interventions: Biological: Human beta common receptor antagonist monoclonal antibody; Drug: Placebo

• Registration Number: NCT04082754
• Lead Sponsor: CSL Behring

Brief Summary

This is a phase 1, first-in-human (FIH), multi-center, randomized, double-blind, placebo-controlled study of CSL311 in patients with mild-to-moderate asthma. The primary objective of this study is to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of CSL311.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-03
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-09
• Study Start: 2019-11-28
• Primary Completion: 2023-11-14
• Study Completion: 2023-11-14
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-09
• Last Update Posted: 2024-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

• Male or female subjects 18 to 65 years of age with diagnosis of mild-to-moderate asthma for Parts A and B. For part C healthy, male or female subjects 18 to 50 years

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Exclusion Criteria

• Oral/parenteral corticosteroids or anti-interleukin-6 therapy within 6 months prior to screening, or any prohibited therapies prior to screening.
• History or presence of clinically significant hypertension or other significant cardiovascular abnormality.
• Any clinically significant abnormality on electrocardiogram at screening.
• Parasitic infestation within 6 months before screening, or travel or intention to travel to a country with a high prevalence of such infections within 1 year before screening or within 85 days after the last dose of CSL311.
• Occurrence of asthma exacerbation and/or upper/lower respiratory tract infection, or any acute infection or disease within the last 6 weeks before screening.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSL311 Cohort A1 (SAD Dose 1)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a Single Ascending Dose (SAD)
CSL311 Cohort A2 (SAD Dose 2)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A3 (SAD Dose 3)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A4 (SAD Dose 4)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A5 (SAD Dose 5)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A6 (SAD Dose 6)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A7 (SAD Dose 7)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort A8 (SAD Dose 8)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
CSL311 Cohort B1 (MAD Dose 1)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered intravenously at a MAD
Placebo	Placebo	0.9% sodium chloride solution administered intravenously
Placebo (2)	Placebo	0.9% sodium chloride solution administered subcutaneously
CSL311 Cohort C1 (MAD Dose 1)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered subcutaneously (SC)
CSL311 Cohort C2 (MAD Dose 2)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered subcutaneously
CSL311 Cohort C3 (MAD Dose 3)	Human beta common receptor antagonist monoclonal antibody	Human beta common receptor antagonist monoclonal antibody administered subcutaneously

Primary Outcome Measures

Name	Time	Method
Percentage of subjects with treatment-emergent adverse events (TEAEs) in SC single dose, single ascending doses (SAD) and multiple ascending doses (MAD - SC and IV)	After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3
Percentage of subjects with related TEAEs in SC single dose, SAD and MAD (SC and IV)	After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3
Percentage of subjects with TEAEs by severity in SC single dose, SAD and MAD (SC and IV)	After infusion or injection, up to Day 85 for Cohorts A1 to A7, Day 57 for Cohort A8, Day 114 for Cohort B1 and Day 85 for Cohorts C1 to C3	Severity of TEAEs defined as mild, moderate, or severe

Secondary Outcome Measures

Name	Time	Method
Half-life (t½) of CSL311 in SAD	Up to 85 days after infusion
Volume of distribution (Vd) of CSL311 in SAD	Up to 85 days after infusion
Maximum plasma concentration (Cmax) of CSL311 in SAD	Up to 85 days after infusion
Time to reach Cmax (tmax) of CSL311 in SAD	Up to 85 days after infusion
Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL311 in SAD	Up to 85 days after infusion
Area under the concentration-time curve from time 0 extrapolated to infinite time (AUC0-inf) of CSL311 in SAD	Up to 85 days after infusion
Clearance (CL) of CSL311 in SAD	Up to 85 days after infusion
Cmax/dose of CSL311 in SAD	Up to 85 days after infusion
AUCtau for CSL311 in MAD (SC and IV) after first dose	Up to 15 days after infusion or injection
Area under the concentration-time curve from time 0 to the last measurable concentration per dose of CSL311 (AUC0-last/dose) in SAD	Up to 85 days after infusion
AUCtau/dose for CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection	Dose-normalized area under the concentration-time curve over a dosing interval
Percentage of subjects with severe or life-threatening Neutropenia in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level	After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Percentage of subjects with TEAEs of Worsening Asthma in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level	After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Cmax/dose of CSL311 in MAD (SC and IV) after first dose	Up to 15 days after infusion or injection	Dose-normalized maximum plasma concentration
Cmax/dose of CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection
Half-life (t½) of CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection
Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose	Up to 85 days after injection
Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose	Up to 114 days after infusion
Number of subjects with detectable anti-CSL311 antibodies in SAD and MAD (SC and IV)	After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Percentage of subjects with TEAEs of Infections and Infestations in SAD and MAD (SC and IV) by treatment (CSL311 or placebo), by causality, and by CSL311 dose level	After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
AUCtau/dose for CSL311 in MAD (SC and IV) after first dose	Up to 15 days after infusion or injection
Cmax of CSL311 in MAD (SC and IV) after first dose	Up to 15 days after infusion or injection
tmax of CSL311 in MAD (SC and IV) after first dose	Up to 15 days after infusion or injection
Cmax of CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection
AUCtau for CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection
tmax of CSL311 in MAD (SC and IV) after last dose	Up to 85 days (SC) and 114 days (IV) after infusion or injection
Clearance (CL) of CSL311 in MAD (IV) after last dose	Up to 114 days after infusion
Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose	Up to 85 days after injection

Trial Locations

Locations (3)

Paraxel Berlin; 🇩🇪 Berlin, Germany

Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM; 🇩🇪 Hannover, Germany

Medicines Evaluation Unit; 🇬🇧 Manchester, United Kingdom