Back to resultsA 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
Primary Purpose
PICC-associated Thrombosis
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
CSL312
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
CSL312 Cohort 1 (Dose 1)
CSL312 Cohort 2 (Dose 2)
CSL312 Cohort 3 (Dose 3)
CSL312 Cohort 4 (Dose 4)
Placebo
Arm Description
CSL312 administered as IV infusion
CSL312 administered as IV infusion
CSL312 administered as IV infusion
CSL312 administered as IV infusion
Placebo administered as IV infusion
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Overall percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Percent of subjects with related TEAEs
Percent of subjects with TEAEs by severity
Number of subjects treated with CSL312 with detectable antibodies to CSL312
Percent of subjects treated with CSL312 with detectable antibodies to CSL312
Maximum plasma concentration (Cmax) of CSL312
Area under the concentration-time curve (AUC0-t) of CSL312
Time of maximum plasma concentration (Tmax) of CSL312
Terminal elimination half-life (T1/2) of CSL312
Total systemic clearance (CLtot) of CSL312
Volume of distribution during the elimination phase (Vz) of CSL312
Accumulation Ratio (AR) of CSL312
Number of subjects with thrombosis-associated catheter occlusion
Percent of subjects with thrombosis-associated catheter occlusion
Number of subjects with PICC removal or replacement
Percent of subjects with PICC removal or replacement
Number of subjects with central line-associated blood stream infections (CLABSI)
Percent of subjects with CLABSI
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04281524
Brief Title
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Business decision non-safety related.
Study Start Date
March 2020 (Anticipated)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
October 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PICC-associated Thrombosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL312 Cohort 1 (Dose 1)
Arm Type
Experimental
Arm Description
CSL312 administered as IV infusion
Arm Title
CSL312 Cohort 2 (Dose 2)
Arm Type
Experimental
Arm Description
CSL312 administered as IV infusion
Arm Title
CSL312 Cohort 3 (Dose 3)
Arm Type
Experimental
Arm Description
CSL312 administered as IV infusion
Arm Title
CSL312 Cohort 4 (Dose 4)
Arm Type
Experimental
Arm Description
CSL312 administered as IV infusion
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered as IV infusion
Intervention Type
Drug
Intervention Name(s)
CSL312
Other Intervention Name(s)
Garadacimab
Intervention Description
CSL312 administered as an IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution of 70% 0.9% saline / 30% CSL312 diluent
Primary Outcome Measure Information:
Title
Number of subjects with PICC-associated thrombosis
Description
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
Time Frame
Up to 29 days after PICC insertion
Title
Percent of subjects with PICC-associated thrombosis
Description
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
Time Frame
Up to 29 days after PICC insertion
Secondary Outcome Measure Information:
Title
Overall percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame
Up to 110 days after first dose of CSL312
Title
Percent of subjects with related TEAEs
Time Frame
Up to 110 days after first dose of CSL312
Title
Percent of subjects with TEAEs by severity
Time Frame
Up to 110 days after first dose of CSL312
Title
Number of subjects treated with CSL312 with detectable antibodies to CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Percent of subjects treated with CSL312 with detectable antibodies to CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Maximum plasma concentration (Cmax) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Area under the concentration-time curve (AUC0-t) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Time of maximum plasma concentration (Tmax) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Terminal elimination half-life (T1/2) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Total systemic clearance (CLtot) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Volume of distribution during the elimination phase (Vz) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Accumulation Ratio (AR) of CSL312
Time Frame
Up to 110 days after first dose of CSL312
Title
Number of subjects with thrombosis-associated catheter occlusion
Time Frame
Up to 29 days after first dose of CSL312
Title
Percent of subjects with thrombosis-associated catheter occlusion
Time Frame
Up to 29 days after first dose of CSL312
Title
Number of subjects with PICC removal or replacement
Time Frame
Up to 29 days after first dose of CSL312
Title
Percent of subjects with PICC removal or replacement
Time Frame
Up to 29 days after first dose of CSL312
Title
Number of subjects with central line-associated blood stream infections (CLABSI)
Time Frame
Up to 29 days after first dose of CSL312
Title
Percent of subjects with CLABSI
Time Frame
Up to 29 days after first dose of CSL312
10. Eligibility
Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
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
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