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

NCT04281524 | Withdrawn Phase 1 DMC

• 1 other identifier: CSL312_1002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

PICC-associated Thrombosis

Outcome Measures

Primary Outcomes (2)

• Number of subjects with PICC-associated thrombosis

  PICC-associated thrombosis which can be either: 1. Asymptomatic PICC associated thrombosis detected by Duplex ultrasound (DUS) or venography at Day 15 or Day 29 after PICC insertion or 2. 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: 1. Asymptomatic PICC associated thrombosis detected by Duplex ultrasound (DUS) or venography at Day 15 or Day 29 after PICC insertion or 2. 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 Outcomes (18)

• 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

Study Arms (5)

CSL312 Cohort 1 (Dose 1)

EXPERIMENTAL

CSL312 administered as IV infusion

Drug: CSL312

CSL312 Cohort 2 (Dose 2)

EXPERIMENTAL

CSL312 administered as IV infusion

Drug: CSL312

CSL312 Cohort 3 (Dose 3)

EXPERIMENTAL

CSL312 administered as IV infusion

Drug: CSL312

CSL312 Cohort 4 (Dose 4)

EXPERIMENTAL

CSL312 administered as IV infusion

Drug: CSL312

Placebo

PLACEBO COMPARATOR

Placebo administered as IV infusion

Drug: Placebo

Interventions

CSL312 DRUG

CSL312 administered as an IV infusion

Also known as: Garadacimab

CSL312 Cohort 1 (Dose 1); CSL312 Cohort 2 (Dose 2); CSL312 Cohort 3 (Dose 3); CSL312 Cohort 4 (Dose 4)

Placebo DRUG

Solution of 70% 0.9% saline / 30% CSL312 diluent

Placebo

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 24, 2020
• Study Start: March 1, 2020
• Primary Completion: August 1, 2021
• Study Completion: October 1, 2021
• Last Updated: March 25, 2020

Record last verified: 2020-03

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.