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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04082754
• Other study ID #: CSL311_1001
• Secondary ID: 2019-001135-32
• Status: Completed
• Phase: Phase 1
• Start date: November 28, 2019
• Est. completion date: November 14, 2023

Study information

• Verified date: January 2024
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: November 14, 2023
• Est. primary completion date: November 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Human beta common receptor antagonist monoclonal antibody
Human beta common receptor antagonist monoclonal antibody

Drug:
• Placebo
0.9% sodium chloride, same volume and same duration as CSL311

Locations

Country	Name	City	State
Germany	Paraxel Berlin	Berlin
Germany	Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM	Hannover
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Percentage of subjects with TEAEs by severity in SC single dose, SAD and MAD (SC and IV)	Severity of TEAEs defined as mild, moderate, or severe	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
Secondary	Maximum plasma concentration (Cmax) of CSL311 in SAD		Up to 85 days after infusion
Secondary	Time to reach Cmax (tmax) of CSL311 in SAD		Up to 85 days after infusion
Secondary	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
Secondary	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
Secondary	Half-life (t½) of CSL311 in SAD		Up to 85 days after infusion
Secondary	Clearance (CL) of CSL311 in SAD		Up to 85 days after infusion
Secondary	Volume of distribution (Vd) of CSL311 in SAD		Up to 85 days after infusion
Secondary	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
Secondary	Cmax/dose of CSL311 in SAD		Up to 85 days after infusion
Secondary	AUCtau for CSL311 in MAD (SC and IV) after first dose		Up to 15 days after infusion or injection
Secondary	AUCtau/dose for CSL311 in MAD (SC and IV) after first dose		Up to 15 days after infusion or injection
Secondary	Cmax of CSL311 in MAD (SC and IV) after first dose		Up to 15 days after infusion or injection
Secondary	Cmax/dose of CSL311 in MAD (SC and IV) after first dose	Dose-normalized maximum plasma concentration	Up to 15 days after infusion or injection
Secondary	tmax of CSL311 in MAD (SC and IV) after first dose		Up to 15 days after infusion or injection
Secondary	Cmax of CSL311 in MAD (SC and IV) after last dose		Up to 85 days (SC) and 114 days (IV) after infusion or injection
Secondary	AUCtau for CSL311 in MAD (SC and IV) after last dose		Up to 85 days (SC) and 114 days (IV) after infusion or injection
Secondary	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
Secondary	tmax of CSL311 in MAD (SC and IV) after last dose		Up to 85 days (SC) and 114 days (IV) after infusion or injection
Secondary	AUCtau/dose for CSL311 in MAD (SC and IV) after last dose	Dose-normalized area under the concentration-time curve over a dosing interval	Up to 85 days (SC) and 114 days (IV) after infusion or injection
Secondary	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
Secondary	Clearance (CL) of CSL311 in MAD (IV) after last dose		Up to 114 days after infusion
Secondary	Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose		Up to 85 days after injection
Secondary	Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose		Up to 114 days after infusion
Secondary	Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose		Up to 85 days after injection
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)