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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Human beta common receptor antagonist monoclonal antibody; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: 610-878-4000; Email: clinicaltrials@cslbehring.com

Study Locations

• Germany
  • Berlin, Germany
    • Paraxel Berlin
  • Hannover, Germany, 30625
    • Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit

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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL311 Cohort A1 (SAD Dose 1); Human beta common receptor antagonist monoclonal antibody administered intravenously at a Single Ascending Dose (SAD)	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A2 (SAD Dose 2); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A3 (SAD Dose 3); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A4 (SAD Dose 4); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A5 (SAD Dose 5); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A6 (SAD Dose 6); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A7 (SAD Dose 7); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort A8 (SAD Dose 8); Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort B1 (MAD Dose 1); Human beta common receptor antagonist monoclonal antibody administered intravenously at a MAD	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Placebo Comparator: Placebo; 0.9% sodium chloride solution administered intravenously	Drug: Placebo; 0.9% sodium chloride, same volume and same duration as CSL311
Placebo Comparator: Placebo (2); 0.9% sodium chloride solution administered subcutaneously	Drug: Placebo; 0.9% sodium chloride, same volume and same duration as CSL311
Experimental: CSL311 Cohort C1 (MAD Dose 1); Human beta common receptor antagonist monoclonal antibody administered subcutaneously (SC)	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort C2 (MAD Dose 2); Human beta common receptor antagonist monoclonal antibody administered subcutaneously	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311
Experimental: CSL311 Cohort C3 (MAD Dose 3); Human beta common receptor antagonist monoclonal antibody administered subcutaneously	Biological: Human beta common receptor antagonist monoclonal antibody; Human beta common receptor antagonist monoclonal antibody; Other Names: CSL311

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Half-life (t½) of CSL311 in SAD		Up to 85 days after infusion
Clearance (CL) of CSL311 in SAD		Up to 85 days after infusion
Volume of distribution (Vd) of CSL311 in SAD		Up to 85 days after infusion
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
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
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
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
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
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
tmax of CSL311 in MAD (SC and IV) after last dose		Up to 85 days (SC) and 114 days (IV) after infusion or injection
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
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
Clearance (CL) of CSL311 in MAD (IV) after last dose		Up to 114 days after infusion
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
Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose		Up to 85 days after injection
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)
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)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Actual): November 14, 2023
• Study Completion (Actual): November 14, 2023

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: CSL311_1001; 2019-001135-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

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 Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made 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