A Study to Assess the Pharmacokinetics and Safety of CSL312 in Healthy Japanese and Caucasian Adults
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Biological: CSL312
- Registration Number
- NCT04580654
- Lead Sponsor
- CSL Behring
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CSL312 (Cohort 2, high dose) CSL312 Factor XIIa antagonist monoclonal antibody administered subcutaneously CSL312 (Cohort 1b, low dose) CSL312 Factor XIIa antagonist monoclonal antibody administered subcutaneously CSL312 (Cohort 4, high dose) CSL312 Factor XIIa antagonist monoclonal antibody administered intravenously CSL312 (Cohort 1a, low dose) CSL312 Factor XIIa antagonist monoclonal antibody administered subcutaneously CSL312 (Cohort 3, low dose) CSL312 Factor XIIa antagonist monoclonal antibody administered intravenously
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 Apparent clearance (CL/F) of CSL312 after subcutaneous dosing Up to 85 days postdose Percentage of subjects experiencing AESIs 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 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 Half-life (t1/2) of CSL312 after subcutaneous dosing 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 Apparent volume of distribution (Vz/F) of CSL312 after subcutaneous dosing Up to 85 days postdose Number of subjects experiencing serious adverse events (SAEs) Up to 85 days postdose Cmax of CSL312 after intravenous dosing Up to 85 days postdose t1/2 of CSL312 after intravenous dosing Up to 85 days postdose Number of subjects experiencing Anti-CSL312 antibodies Up to 85 days postdose Percentage of subjects with injection / infusion site reaction by severity Up to 48 hours after start of infusion or injection 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 Mean FXIIa-mediated kallikrein activity 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 Percentage of subjects experiencing Anti-CSL312 antibodies Up to 85 days postdose
Trial Locations
- Locations (1)
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States