Asthma
Conditions
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.
Interventions
BIOLOGICALHuman beta common receptor antagonist monoclonal antibody
Human beta common receptor antagonist monoclonal antibody
DRUGPlacebo
0.9% sodium chloride, same volume and same duration as CSL311
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 |
| 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 first dose | Up to 15 days 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 | 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 |
| 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) | — |
| AUCtau for 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 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 | — |
Countries
Germany, United Kingdom
Outcome results
None listed