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

• ClinicalTrials.gov Identifier: NCT04281524
• Recruitment Status: Withdrawn
• First Posted: February 24, 2020
• Last Update Posted: March 25, 2020
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

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.

Condition or disease	Intervention/treatment	Phase
PICC-associated Thrombosis	Drug: CSL312; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Estimated Study Start Date: March 2020
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: October 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: CSL312 Cohort 1 (Dose 1); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Name: Garadacimab
Experimental: CSL312 Cohort 2 (Dose 2); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Name: Garadacimab
Experimental: CSL312 Cohort 3 (Dose 3); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Name: Garadacimab
Experimental: CSL312 Cohort 4 (Dose 4); CSL312 administered as IV infusion	Drug: CSL312; CSL312 administered as an IV infusion; Other Name: Garadacimab
Placebo Comparator: Placebo; Placebo administered as IV infusion	Drug: Placebo; Solution of 70% 0.9% saline / 30% CSL312 diluent

Outcome Measures

Primary Outcome Measures :

1. Number of subjects with PICC-associated thrombosis [ Time Frame: 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
2. Percent of subjects with PICC-associated thrombosis [ Time Frame: 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 :

1. 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 ]
2. Percent of subjects with related TEAEs [ Time Frame: Up to 110 days after first dose of CSL312 ]
3. Percent of subjects with TEAEs by severity [ Time Frame: Up to 110 days after first dose of CSL312 ]
4. Number of subjects treated with CSL312 with detectable antibodies to CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
5. Percent of subjects treated with CSL312 with detectable antibodies to CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
6. Maximum plasma concentration (Cmax) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
7. Area under the concentration-time curve (AUC0-t) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
8. Time of maximum plasma concentration (Tmax) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
9. Terminal elimination half-life (T1/2) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
10. Total systemic clearance (CLtot) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
11. Volume of distribution during the elimination phase (Vz) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
12. Accumulation Ratio (AR) of CSL312 [ Time Frame: Up to 110 days after first dose of CSL312 ]
13. Number of subjects with thrombosis-associated catheter occlusion [ Time Frame: Up to 29 days after first dose of CSL312 ]
14. Percent of subjects with thrombosis-associated catheter occlusion [ Time Frame: Up to 29 days after first dose of CSL312 ]
15. Number of subjects with PICC removal or replacement [ Time Frame: Up to 29 days after first dose of CSL312 ]
16. Percent of subjects with PICC removal or replacement [ Time Frame: Up to 29 days after first dose of CSL312 ]
17. Number of subjects with central line-associated blood stream infections (CLABSI) [ Time Frame: Up to 29 days after first dose of CSL312 ]
18. Percent of subjects with CLABSI [ Time Frame: Up to 29 days after first dose of CSL312 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

CSL Behring

Investigators

• Study Director: Study Director; CSL Behring

More Information

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT04281524
• Other Study ID Numbers: CSL312_1002
• First Posted: February 24, 2020
• Last Update Posted: March 25, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases