Back to resultsA Clinical Study to Test the Safety, Exposure, and Pharmacodynamic Markers of CSL311 in Patients With Mild-to-moderate Asthma and in Healthy Volunteers
Primary Purpose
Asthma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Human beta common receptor antagonist monoclonal antibody
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma
Eligibility Criteria
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.
Sites / Locations
- Paraxel BerlinRecruiting
- Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEMRecruiting
- Hammersmith Medicines Research
- Medicines Evaluation UnitRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
CSL311 Cohort A1 (SAD Dose 1)
CSL311 Cohort A2 (SAD Dose 2)
CSL311 Cohort A3 (SAD Dose 3)
CSL311 Cohort A4 (SAD Dose 4)
CSL311 Cohort A5 (SAD Dose 5)
CSL311 Cohort A6 (SAD Dose 6)
CSL311 Cohort A7 (SAD Dose 7)
CSL311 Cohort A8 (SAD Dose 8)
CSL311 Cohort B1 (MAD Dose 1)
Placebo
Placebo (2)
CSL311 Cohort C1 (MAD Dose 1)
CSL311 Cohort C2 (MAD Dose 2)
CSL311 Cohort C3 (MAD Dose 3)
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a Single Ascending Dose (SAD)
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Human beta common receptor antagonist monoclonal antibody administered intravenously at a MAD
0.9% sodium chloride solution administered intravenously
0.9% sodium chloride solution administered subcutaneously
Human beta common receptor antagonist monoclonal antibody administered subcutaneously (SC)
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
Outcomes
Primary Outcome Measures
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)
Percentage of subjects with related TEAEs in SC single dose, SAD and MAD (SC and IV)
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
Secondary Outcome Measures
Maximum plasma concentration (Cmax) of CSL311 in SAD
Time to reach Cmax (tmax) of CSL311 in SAD
Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL311 in SAD
Area under the concentration-time curve from time 0 extrapolated to infinite time (AUC0-inf) of CSL311 in SAD
Half-life (t½) of CSL311 in SAD
Clearance (CL) of CSL311 in SAD
Volume of distribution (Vd) of CSL311 in SAD
Area under the concentration-time curve from time 0 to the last measurable concentration per dose of CSL311 (AUC0-last/dose) in SAD
Cmax/dose of CSL311 in SAD
AUCtau for CSL311 in MAD (SC and IV) after first dose
AUCtau/dose for CSL311 in MAD (SC and IV) after first dose
Cmax of CSL311 in MAD (SC and IV) after first dose
Cmax/dose of CSL311 in MAD (SC and IV) after first dose
Dose-normalized maximum plasma concentration
tmax of CSL311 in MAD (SC and IV) after first dose
Cmax of CSL311 in MAD (SC and IV) after last dose
AUCtau for CSL311 in MAD (SC and IV) after last dose
Cmax/dose of CSL311 in MAD (SC and IV) after last dose
tmax of CSL311 in MAD (SC and IV) after last dose
AUCtau/dose for CSL311 in MAD (SC and IV) after last dose
Dose-normalized area under the concentration-time curve over a dosing interval
Half-life (t½) of CSL311 in MAD (SC and IV) after last dose
Clearance (CL) of CSL311 in MAD (IV) after last dose
Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose
Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose
Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose
Number of subjects with detectable anti-CSL311 antibodies in SAD and MAD (SC and 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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04082754
Brief Title
A Clinical Study to Test the Safety, Exposure, and Pharmacodynamic Markers of CSL311 in Patients With Mild-to-moderate Asthma and in Healthy Volunteers
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 28, 2019 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
82 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CSL311 Cohort A1 (SAD Dose 1)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a Single Ascending Dose (SAD)
Arm Title
CSL311 Cohort A2 (SAD Dose 2)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A3 (SAD Dose 3)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A4 (SAD Dose 4)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A5 (SAD Dose 5)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A6 (SAD Dose 6)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A7 (SAD Dose 7)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort A8 (SAD Dose 8)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a SAD
Arm Title
CSL311 Cohort B1 (MAD Dose 1)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered intravenously at a MAD
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% sodium chloride solution administered intravenously
Arm Title
Placebo (2)
Arm Type
Placebo Comparator
Arm Description
0.9% sodium chloride solution administered subcutaneously
Arm Title
CSL311 Cohort C1 (MAD Dose 1)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered subcutaneously (SC)
Arm Title
CSL311 Cohort C2 (MAD Dose 2)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
Arm Title
CSL311 Cohort C3 (MAD Dose 3)
Arm Type
Experimental
Arm Description
Human beta common receptor antagonist monoclonal antibody administered subcutaneously
Intervention Type
Biological
Intervention Name(s)
Human beta common receptor antagonist monoclonal antibody
Other Intervention Name(s)
CSL311
Intervention Description
Human beta common receptor antagonist monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% sodium chloride, same volume and same duration as CSL311
Primary Outcome Measure Information:
Title
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)
Time Frame
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
Title
Percentage of subjects with related TEAEs in SC single dose, SAD and MAD (SC and IV)
Time Frame
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
Title
Percentage of subjects with TEAEs by severity in SC single dose, SAD and MAD (SC and IV)
Description
Severity of TEAEs defined as mild, moderate, or severe
Time Frame
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 Measure Information:
Title
Maximum plasma concentration (Cmax) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Time to reach Cmax (tmax) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Area under the concentration-time curve from time 0 extrapolated to infinite time (AUC0-inf) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Half-life (t½) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Clearance (CL) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Volume of distribution (Vd) of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
Area under the concentration-time curve from time 0 to the last measurable concentration per dose of CSL311 (AUC0-last/dose) in SAD
Time Frame
Up to 85 days after infusion
Title
Cmax/dose of CSL311 in SAD
Time Frame
Up to 85 days after infusion
Title
AUCtau for CSL311 in MAD (SC and IV) after first dose
Time Frame
Up to 15 days after infusion or injection
Title
AUCtau/dose for CSL311 in MAD (SC and IV) after first dose
Time Frame
Up to 15 days after infusion or injection
Title
Cmax of CSL311 in MAD (SC and IV) after first dose
Time Frame
Up to 15 days after infusion or injection
Title
Cmax/dose of CSL311 in MAD (SC and IV) after first dose
Description
Dose-normalized maximum plasma concentration
Time Frame
Up to 15 days after infusion or injection
Title
tmax of CSL311 in MAD (SC and IV) after first dose
Time Frame
Up to 15 days after infusion or injection
Title
Cmax of CSL311 in MAD (SC and IV) after last dose
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
AUCtau for CSL311 in MAD (SC and IV) after last dose
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
Cmax/dose of CSL311 in MAD (SC and IV) after last dose
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
tmax of CSL311 in MAD (SC and IV) after last dose
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
AUCtau/dose for CSL311 in MAD (SC and IV) after last dose
Description
Dose-normalized area under the concentration-time curve over a dosing interval
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
Half-life (t½) of CSL311 in MAD (SC and IV) after last dose
Time Frame
Up to 85 days (SC) and 114 days (IV) after infusion or injection
Title
Clearance (CL) of CSL311 in MAD (IV) after last dose
Time Frame
Up to 114 days after infusion
Title
Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose
Time Frame
Up to 85 days after injection
Title
Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose
Time Frame
Up to 114 days after infusion
Title
Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose
Time Frame
Up to 85 days after injection
Title
Number of subjects with detectable anti-CSL311 antibodies in SAD and MAD (SC and IV)
Time Frame
After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Title
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
Time Frame
After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Title
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
Time Frame
After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Title
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
Time Frame
After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Registration Coordinator
Phone
610-878-4000
Email
clinicaltrials@cslbehring.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Paraxel Berlin
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
USE CENTRAL CONTACT
Facility Name
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
USE CENTRAL CONTACT
Facility Name
Hammersmith Medicines Research
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom
Individual Site Status
Withdrawn
Facility Name
Medicines Evaluation Unit
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
USE CENTRAL CONTACT
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
A Clinical Study to Test the Safety, Exposure, and Pharmacodynamic Markers of CSL311 in Patients With Mild-to-moderate Asthma and in Healthy Volunteers
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