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

NCT04580654 | Completed Phase 1 FDA Drug

• 1 other identifier: CSL312_1003
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (23)

• 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

Study Arms (5)

CSL312 (Cohort 1a, low dose)

EXPERIMENTAL

Factor XIIa antagonist monoclonal antibody administered subcutaneously

Biological: CSL312

CSL312 (Cohort 1b, low dose)

EXPERIMENTAL

Factor XIIa antagonist monoclonal antibody administered subcutaneously

Biological: CSL312

CSL312 (Cohort 2, high dose)

EXPERIMENTAL

Factor XIIa antagonist monoclonal antibody administered subcutaneously

Biological: CSL312

CSL312 (Cohort 3, low dose)

EXPERIMENTAL

Factor XIIa antagonist monoclonal antibody administered intravenously

Biological: CSL312

CSL312 (Cohort 4, high dose)

EXPERIMENTAL

Factor XIIa antagonist monoclonal antibody administered intravenously

Biological: CSL312

Interventions

CSL312 BIOLOGICAL

Fully human immunoglobulin G4/lambda recombinant monoclonal antibody against Factor XIIa

Also known as: Factor XIIa antagonist monoclonal antibody, garadacimab

CSL312 (Cohort 1a, low dose); CSL312 (Cohort 1b, low dose); CSL312 (Cohort 2, high dose); CSL312 (Cohort 3, low dose); CSL312 (Cohort 4, high dose)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (1)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: October 29, 2020
• Primary Completion: May 7, 2021
• Study Completion: May 7, 2021
• Last Updated: October 4, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (1)