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

Phase 1

Withdrawn

• Conditions: PICC-associated Thrombosis
• Interventions: Drug: CSL312; Drug: Placebo

• Registration Number: NCT04281524
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-21
• Study First Submitted QC: 2020-02-21
• Study First Posted: 2020-02-24
• Status Verified: 2020-03
• Study Start: 2020-03
• Last Update Submitted: 2020-03-23
• Last Update Posted: 2020-03-25
• Primary Completion: 2021-08
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSL312 Cohort 4 (Dose 4)	CSL312	CSL312 administered as IV infusion
Placebo	Placebo	Placebo administered as IV infusion
CSL312 Cohort 1 (Dose 1)	CSL312	CSL312 administered as IV infusion
CSL312 Cohort 2 (Dose 2)	CSL312	CSL312 administered as IV infusion
CSL312 Cohort 3 (Dose 3)	CSL312	CSL312 administered as IV infusion

Primary Outcome Measures

Name	Time	Method
Percent of subjects with PICC-associated thrombosis	Up to 29 days after PICC insertion	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
Number of subjects with PICC-associated thrombosis	Up to 29 days after PICC insertion	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

Secondary Outcome Measures

Name	Time	Method
Number of subjects with central line-associated blood stream infections (CLABSI)	Up to 29 days after first dose of CSL312
Maximum plasma concentration (Cmax) of CSL312	Up to 110 days after first dose of CSL312
Percent of subjects with thrombosis-associated catheter occlusion	Up to 29 days after first dose of CSL312
Percent of subjects with CLABSI	Up to 29 days after first dose of CSL312
Terminal elimination half-life (T1/2) of CSL312	Up to 110 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
Percent of subjects with related TEAEs	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
Volume of distribution during the elimination phase (Vz) 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
Overall percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Up to 110 days after first dose of CSL312
Accumulation Ratio (AR) of CSL312	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
Percent of subjects treated with CSL312 with detectable antibodies to 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
Total systemic clearance (CLtot) of CSL312	Up to 110 days after first dose of CSL312