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.

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