Clinical trial NCT04580654: A Study to Assess the Pharmacokinetics and Safety of CSL312 in Healthy Japanese and Caucasian Adults
Official title: A 2-Part, Phase 1, Single Center, Open-label, Single Ascending Dose Study to Investigate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Subcutaneous and Intravenous CSL312 in Healthy Adult Japanese and Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-inf) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
Secondary outcomes:
measure: Time to maximum concentration (Tmax) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Half-life (t1/2) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Apparent clearance (CL/F) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Apparent volume of distribution (Vz/F) of CSL312 after subcutaneous dosing
timeFrame: Up to 85 days postdose
measure: Cmax of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: Tmax of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: AUC0-last of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: AUC0-inf of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: t1/2 of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: Clearance (CL) of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: Volume of distribution (Vd) of CSL312 after intravenous dosing
timeFrame: Up to 85 days postdose
measure: Mean FXIIa-mediated kallikrein activity
timeFrame: Up to 85 days postdose
measure: Number of subjects experiencing adverse events (AEs)
timeFrame: Up to 85 days postdose
measure: Percentage of subjects experiencing AEs
timeFrame: Up to 85 days postdose
measure: Number of subjects experiencing serious adverse events (SAEs)
timeFrame: Up to 85 days postdose
measure: Percentage of subjects experiencing SAEs
timeFrame: Up to 85 days postdose
measure: Number of subjects experiencing adverse events of special interest (AESIs)
timeFrame: Up to 85 days postdose
measure: Percentage of subjects experiencing AESIs
timeFrame: Up to 85 days postdose
measure: Number of subjects experiencing Anti-CSL312 antibodies
timeFrame: Up to 85 days postdose
measure: Percentage of subjects experiencing Anti-CSL312 antibodies
timeFrame: Up to 85 days postdose
measure: Number of subjects with injection / infusion site reaction by severity
timeFrame: Up to 48 hours after start of infusion or injection
measure: Percentage of subjects with injection / infusion site reaction by severity
timeFrame: Up to 48 hours after start of infusion or injection
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: