A Study to Assess the Pharmacokinetics and Safety of CSL312 in Healthy Japanese and Caucasian Adults

Sponsor

CSL Behring (Industry)

Overall Status

Completed

CT.gov ID

NCT04580654

Collaborator

(none)

Enrollment

Location

Arms

6.2

Actual Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Biological: CSL312	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Actual Study Start Date :

Oct 29, 2020

Actual Primary Completion Date :

May 7, 2021

Actual Study Completion Date :

May 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CSL312 (Cohort 1a, low dose) Factor XIIa antagonist monoclonal antibody administered subcutaneously	Biological: CSL312 Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa Other Names: Factor XIIa antagonist monoclonal antibody garadacimab
Experimental: CSL312 (Cohort 1b, low dose) Factor XIIa antagonist monoclonal antibody administered subcutaneously	Biological: CSL312 Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa Other Names: Factor XIIa antagonist monoclonal antibody garadacimab
Experimental: CSL312 (Cohort 2, high dose) Factor XIIa antagonist monoclonal antibody administered subcutaneously	Biological: CSL312 Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa Other Names: Factor XIIa antagonist monoclonal antibody garadacimab
Experimental: CSL312 (Cohort 3, low dose) Factor XIIa antagonist monoclonal antibody administered intravenously	Biological: CSL312 Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa Other Names: Factor XIIa antagonist monoclonal antibody garadacimab
Experimental: CSL312 (Cohort 4, high dose) Factor XIIa antagonist monoclonal antibody administered intravenously	Biological: CSL312 Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa Other Names: Factor XIIa antagonist monoclonal antibody garadacimab

Outcome Measures

Primary Outcome Measures

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

Time to maximum concentration (Tmax) of CSL312 after subcutaneous dosing [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]
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]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801

Sponsors and Collaborators

CSL Behring

Investigators

Study Director: Study Director, CSL Behring

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

CSL Behring

ClinicalTrials.gov Identifier:

NCT04580654

Other Study ID Numbers:

CSL312_1003

First Posted:

Oct 8, 2020

Last Update Posted:

Jun 8, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Jun 8, 2022