Clinical trial NCT04281524: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: PICC-associated Thrombosis
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-02-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with PICC-associated thrombosis
timeFrame: Up to 29 days after PICC insertion
measure: Percent of subjects with PICC-associated thrombosis
timeFrame: Up to 29 days after PICC insertion
Secondary outcomes:
measure: Overall percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Up to 110 days after first dose of CSL312
measure: Percent of subjects with related TEAEs
timeFrame: Up to 110 days after first dose of CSL312
measure: Percent of subjects with TEAEs by severity
timeFrame: Up to 110 days after first dose of CSL312
measure: Number of subjects treated with CSL312 with detectable antibodies to CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Percent of subjects treated with CSL312 with detectable antibodies to CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Maximum plasma concentration (Cmax) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Area under the concentration-time curve (AUC0-t) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Time of maximum plasma concentration (Tmax) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Terminal elimination half-life (T1/2) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Total systemic clearance (CLtot) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Volume of distribution during the elimination phase (Vz) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Accumulation Ratio (AR) of CSL312
timeFrame: Up to 110 days after first dose of CSL312
measure: Number of subjects with thrombosis-associated catheter occlusion
timeFrame: Up to 29 days after first dose of CSL312
measure: Percent of subjects with thrombosis-associated catheter occlusion
timeFrame: Up to 29 days after first dose of CSL312
measure: Number of subjects with PICC removal or replacement
timeFrame: Up to 29 days after first dose of CSL312
measure: Percent of subjects with PICC removal or replacement
timeFrame: Up to 29 days after first dose of CSL312
measure: Number of subjects with central line-associated blood stream infections (CLABSI)
timeFrame: Up to 29 days after first dose of CSL312
measure: Percent of subjects with CLABSI
timeFrame: Up to 29 days after first dose of CSL312
Other outcomes:
Locations:
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: