Healthy Volunteers
Conditions
Brief summary
This will be a 2- part, phase 1, open-label, single center, single ascending dose study to investigate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of subcutaneous (SC) and intravenous (IV) administration of CSL312 in healthy adult Japanese and Caucasian subjects.
Interventions
BIOLOGICALCSL312
Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa
Sponsors
CSL Behring
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Caucasian and Japanese male or female subjects 18 to 55 years old (inclusive) that meet the following criteria at Screening: * Japanese subjects defined as being born in Japan, having not lived outside of Japan for more than 10 years, and having both parents and four grandparents who are of Japanese ancestry. * Caucasian subjects, defined as having both parents and four grandparents descended from and of the peoples of Europe, the Middle East, or North Africa, who are body weight-matched (± 15%) 1:1 with Japanese subjects. * Body weight in the range of ≥ 50 kg and ≤ 100 kg * Body mass index of ≥ 18 kg/m2 and ≤ 30 kg/m2
Exclusion criteria
* Positive serology test for human immunodeficiency virus (HIV)-1 / 2 antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis C virus (HCV) antibody. * Received any live viral or bacterial vaccinations within 8 weeks of Screening or is expected to receive any live virus or bacterial vaccinations during the study. * Evidence of current active infection. * Known malignancy or a history of malignancy in the past 5 years . * Blood pressure or pulse rate measurements outside the normal range for the subject's age. * Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception * Pregnant, breastfeeding, or not willing to cease breastfeeding. * Donation or loss of more than 500 mL of blood within 3 months, or donated plasma within 7 days * History of clinically significant arterial or venous thrombosis, bleeding disorder, or any abnormal coagulation test result
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
| Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-inf) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
Secondary
| Measure | Time frame |
|---|---|
| Half-life (t1/2) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
| Apparent clearance (CL/F) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
| Apparent volume of distribution (Vz/F) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
| Cmax of CSL312 after intravenous dosing | Up to 85 days postdose |
| Tmax of CSL312 after intravenous dosing | Up to 85 days postdose |
| AUC0-last of CSL312 after intravenous dosing | Up to 85 days postdose |
| AUC0-inf of CSL312 after intravenous dosing | Up to 85 days postdose |
| t1/2 of CSL312 after intravenous dosing | Up to 85 days postdose |
| Clearance (CL) of CSL312 after intravenous dosing | Up to 85 days postdose |
| Volume of distribution (Vd) of CSL312 after intravenous dosing | Up to 85 days postdose |
| Time to maximum concentration (Tmax) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
| Number of subjects experiencing adverse events (AEs) | Up to 85 days postdose |
| Percentage of subjects experiencing AEs | Up to 85 days postdose |
| Number of subjects experiencing serious adverse events (SAEs) | Up to 85 days postdose |
| Percentage of subjects experiencing SAEs | Up to 85 days postdose |
| Number of subjects experiencing adverse events of special interest (AESIs) | Up to 85 days postdose |
| Percentage of subjects experiencing AESIs | Up to 85 days postdose |
| Number of subjects experiencing Anti-CSL312 antibodies | Up to 85 days postdose |
| Percentage of subjects experiencing Anti-CSL312 antibodies | Up to 85 days postdose |
| Number of subjects with injection / infusion site reaction by severity | Up to 48 hours after start of infusion or injection |
| Percentage of subjects with injection / infusion site reaction by severity | Up to 48 hours after start of infusion or injection |
| Mean FXIIa-mediated kallikrein activity | Up to 85 days postdose |
| Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL312 after subcutaneous dosing | Up to 85 days postdose |
Countries
United States
Outcome results
None listed