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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: CSL312

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2020
• Primary Completion (Actual): May 7, 2021
• Study Completion (Actual): May 7, 2021

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CSL312_1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No