A Clinical Study to Test the Efficacy and Safety of CSL312 on Catheter-associated Blood Clot Formation in Subjects With Cancer Who Receive Chemotherapy Through a PICC Line

A Phase 1b, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, and Pharmacokinetics of CSL312 in the Prevention of Peripherally Inserted Central Catheter (PICC)-Associated Thrombosis in Subjects With Cancer

Peripherally Inserted Central Catheters (PICCs) are commonly used in patients with cancer to administer chemotherapy and supportive care medication. However, PICCs and other medical devices that come into contact with blood increase the risk of blood clots (thrombosis) inside the blood vessels. Conventional blood thinners (anticoagulants) may reduce the risk of thrombosis but they also increase the risk of bleeding. CSL312, a monoclonal antibody that inhibits the activated blood clotting factor 12 (FXIIa) will be assessed for its potential to prevent thrombus formation in subjects with cancer at risk of PICC-associated thrombosis.

Study Overview

• Status: Withdrawn
• Conditions: PICC-associated Thrombosis
• Intervention / Treatment: Drug: CSL312; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years or older at the time of providing written informed consent
• Diagnosis of malignancy that requires placement of a PICC within the next 3 weeks for administration of chemotherapy (PICC anticipated to be required for at least 1 month)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 [Oken et al, 1982], and investigator's expectation that performance status will remain 0, 1, or 2 for the duration of the study

Exclusion Criteria:

• Active bleeding or with a current clinically significant coagulopathy (eg, international normalized ratio [INR] > 1.5) or clinically significant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks)
• History of venous thrombosis, myocardial infarction or cerebrovascular event within 3 months, or a prothrombotic disorder (eg, antithrombin III, protein C or S deficiency)
• Life expectancy less than study duration (110 days)
• Platelet count of < 20 × 109/L on the day of dose 1 (Day 1) or within 7 days before first dosing
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2
• Treatment with antiplatelet or anticoagulant medication, including thrombosis prophylaxis, within 10 days prior to insertion of the PICC
• Chemotherapy regimen that would be expected to drop the platelet count to < 20 × 109/L
• Chemotherapy regimen with heparin mixed into IV bags (eg, dalteparin 2500 IU/day)
• Difficult IV access that would prevent infusion of the IP
• In situ central venous catheter (CVC) or PICC in the 3 months before the Screening Visit. The study PICC must be inserted in the contralateral side, which must be PICC / CVC naïve
• Undergoing dialysis or have another inserted intravascular foreign surface device
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≥ 4 × upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CSL312 Cohort 1 (Dose 1); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Names: Garadacimab
EXPERIMENTAL: CSL312 Cohort 2 (Dose 2); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Names: Garadacimab
EXPERIMENTAL: CSL312 Cohort 3 (Dose 3); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Names: Garadacimab
EXPERIMENTAL: CSL312 Cohort 4 (Dose 4); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Names: Garadacimab
PLACEBO_COMPARATOR: Placebo; Placebo administered as IV infusion	Drug: Placebo; Solution of 70% 0.9% saline / 30% CSL312 diluent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with PICC-associated thrombosis	PICC-associated thrombosis which can be either: Asymptomatic PICC associated thrombosis detected by Duplex ultrasound (DUS) or venography at Day 15 or Day 29 after PICC insertion or; Symptomatic PICC associated thrombosis up to Day 29 after PICC insertion, suspected clinically due to symptoms of the upper limb or neck, and objectively confirmed by DUS or venography	Up to 29 days after PICC insertion
Percent of subjects with PICC-associated thrombosis	PICC-associated thrombosis which can be either: Asymptomatic PICC associated thrombosis detected by Duplex ultrasound (DUS) or venography at Day 15 or Day 29 after PICC insertion or; Symptomatic PICC associated thrombosis up to Day 29 after PICC insertion, suspected clinically due to symptoms of the upper limb or neck, and objectively confirmed by DUS or venography	Up to 29 days after PICC insertion

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Up to 110 days after first dose of CSL312
Percent of subjects with related TEAEs	Up to 110 days after first dose of CSL312
Percent of subjects with TEAEs by severity	Up to 110 days after first dose of CSL312
Number of subjects treated with CSL312 with detectable antibodies to CSL312	Up to 110 days after first dose of CSL312
Percent of subjects treated with CSL312 with detectable antibodies to CSL312	Up to 110 days after first dose of CSL312
Maximum plasma concentration (Cmax) of CSL312	Up to 110 days after first dose of CSL312
Area under the concentration-time curve (AUC0-t) of CSL312	Up to 110 days after first dose of CSL312
Time of maximum plasma concentration (Tmax) of CSL312	Up to 110 days after first dose of CSL312
Terminal elimination half-life (T1/2) of CSL312	Up to 110 days after first dose of CSL312
Total systemic clearance (CLtot) of CSL312	Up to 110 days after first dose of CSL312
Volume of distribution during the elimination phase (Vz) of CSL312	Up to 110 days after first dose of CSL312
Accumulation Ratio (AR) of CSL312	Up to 110 days after first dose of CSL312
Number of subjects with thrombosis-associated catheter occlusion	Up to 29 days after first dose of CSL312
Percent of subjects with thrombosis-associated catheter occlusion	Up to 29 days after first dose of CSL312
Number of subjects with PICC removal or replacement	Up to 29 days after first dose of CSL312
Percent of subjects with PICC removal or replacement	Up to 29 days after first dose of CSL312
Number of subjects with central line-associated blood stream infections (CLABSI)	Up to 29 days after first dose of CSL312
Percent of subjects with CLABSI	Up to 29 days after first dose of CSL312

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2020
• Primary Completion (ANTICIPATED): August 1, 2021
• Study Completion (ANTICIPATED): October 1, 2021

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (ACTUAL): February 24, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: CSL312_1002

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; SAP

Drug and device information, study documents

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