Clinical trial NCT04082754: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-09-09
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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)
timeFrame: 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
measure: Percentage of subjects with related TEAEs in SC single dose, SAD and MAD (SC and IV)
timeFrame: 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
measure: Percentage of subjects with TEAEs by severity in SC single dose, SAD and MAD (SC and IV)
timeFrame: 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 outcomes:
measure: Maximum plasma concentration (Cmax) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Time to reach Cmax (tmax) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Area under the concentration-time curve from time 0 extrapolated to infinite time (AUC0-inf) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Half-life (t½) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Clearance (CL) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Volume of distribution (Vd) of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: Area under the concentration-time curve from time 0 to the last measurable concentration per dose of CSL311 (AUC0-last/dose) in SAD
timeFrame: Up to 85 days after infusion
measure: Cmax/dose of CSL311 in SAD
timeFrame: Up to 85 days after infusion
measure: AUCtau for CSL311 in MAD (SC and IV) after first dose
timeFrame: Up to 15 days after infusion or injection
measure: AUCtau/dose for CSL311 in MAD (SC and IV) after first dose
timeFrame: Up to 15 days after infusion or injection
measure: Cmax of CSL311 in MAD (SC and IV) after first dose
timeFrame: Up to 15 days after infusion or injection
measure: Cmax/dose of CSL311 in MAD (SC and IV) after first dose
timeFrame: Up to 15 days after infusion or injection
measure: tmax of CSL311 in MAD (SC and IV) after first dose
timeFrame: Up to 15 days after infusion or injection
measure: Cmax of CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: AUCtau for CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: Cmax/dose of CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: tmax of CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: AUCtau/dose for CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: Half-life (t½) of CSL311 in MAD (SC and IV) after last dose
timeFrame: Up to 85 days (SC) and 114 days (IV) after infusion or injection
measure: Clearance (CL) of CSL311 in MAD (IV) after last dose
timeFrame: Up to 114 days after infusion
measure: Apparent Clearance (CL/F) of CSL311 in MAD (SC) after last dose
timeFrame: Up to 85 days after injection
measure: Volume of distribution (Vd) of CSL311 in MAD (IV) after last dose
timeFrame: Up to 114 days after infusion
measure: Apparent volume of distribution during terminal phase (Vz/F) of CSL311 in MAD (SC) after last dose
timeFrame: Up to 85 days after injection
measure: Number of subjects with detectable anti-CSL311 antibodies in SAD and MAD (SC and IV)
timeFrame: After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
measure: 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
timeFrame: After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
measure: 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
timeFrame: After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
measure: 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
timeFrame: After infusion or injection, up to 85 days for SAD, and up to 85 days for MAD (SC) and 114 days for MAD (IV)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Paraxel Berlin
city: Hannover
country: Germany
facility: Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: