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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04580654
Recruitment Status : Completed
First Posted : October 8, 2020
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Biological: CSL312 Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : October 29, 2020
Actual Primary Completion Date : May 7, 2021
Actual Study Completion Date : May 7, 2021

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




Primary Outcome Measures :
  1. Maximum plasma concentration (Cmax) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  2. Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-inf) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]

Secondary Outcome Measures :
  1. Time to maximum concentration (Tmax) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  2. Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  3. Half-life (t1/2) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  4. Apparent clearance (CL/F) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  5. Apparent volume of distribution (Vz/F) of CSL312 after subcutaneous dosing [ Time Frame: Up to 85 days postdose ]
  6. Cmax of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  7. Tmax of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  8. AUC0-last of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  9. AUC0-inf of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  10. t1/2 of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  11. Clearance (CL) of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  12. Volume of distribution (Vd) of CSL312 after intravenous dosing [ Time Frame: Up to 85 days postdose ]
  13. Mean FXIIa-mediated kallikrein activity [ Time Frame: Up to 85 days postdose ]
  14. Number of subjects experiencing adverse events (AEs) [ Time Frame: Up to 85 days postdose ]
  15. Percentage of subjects experiencing AEs [ Time Frame: Up to 85 days postdose ]
  16. Number of subjects experiencing serious adverse events (SAEs) [ Time Frame: Up to 85 days postdose ]
  17. Percentage of subjects experiencing SAEs [ Time Frame: Up to 85 days postdose ]
  18. Number of subjects experiencing adverse events of special interest (AESIs) [ Time Frame: Up to 85 days postdose ]
  19. Percentage of subjects experiencing AESIs [ Time Frame: Up to 85 days postdose ]
  20. Number of subjects experiencing Anti-CSL312 antibodies [ Time Frame: Up to 85 days postdose ]
  21. Percentage of subjects experiencing Anti-CSL312 antibodies [ Time Frame: Up to 85 days postdose ]
  22. Number of subjects with injection / infusion site reaction by severity [ Time Frame: Up to 48 hours after start of infusion or injection ]
  23. Percentage of subjects with injection / infusion site reaction by severity [ Time Frame: Up to 48 hours after start of infusion or injection ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04580654


Locations
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United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92801
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Study Director CSL Behring
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT04580654    
Other Study ID Numbers: CSL312_1003
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: October 4, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No