Monitoring of Anti-TFPI in Hemophilia
EUREKA
1 other identifier
observational
11
1 country
2
Brief Summary
During the development of anti-TFPI antibodies, thrombin generation assay (TGA) was employed using both in vitro measurements (antibodies added to blood samples) and ex vivo approaches (blood samples from patients in phase II and III trials). While a significant improvement in thrombin generation was observed in all samples from patients with severe hemophilia, no correlation with clinical outcomes could be established. Notably, thrombin peak levels were consistently improved even in patients who experienced bleeding episodes. These measurements were conducted in platelet-poor plasma (PPP) with standard reagents, which may not adequately reflect the hemostatic efficacy of anti-TFPI antibodies given their mechanism of action. It is hypothesized that optimizing reagents and utilizing more appropriate biological materials could enhance TGA sensitivity, as previously demonstrated for monitoring emicizumab. The absence of a laboratory assay to monitor anti-TFPI (tissue factor pathway inhibitor) antibodies poses a significant challenge for managing patients in surgical settings and treating acute severe bleeding. This study aims to develop a reliable assay to evaluate the hemostatic efficacy of anti-TFPI antibodies and their combined procoagulant effect with factor concentrates (FVIII or FIX) or bypassing agents.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Oct 2025
Shorter than P25 for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2025
CompletedFirst Posted
Study publicly available on registry
August 3, 2025
CompletedStudy Start
First participant enrolled
October 23, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2026
March 23, 2026
March 1, 2026
9 months
July 28, 2025
March 19, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Development of a Laboratory Assay to Assess Hemostatic Efficacy of Anti-TFPI Antibodies
Assessment of the thrombin generation assay's ability to evaluate the procoagulant effect of anti-TFPI antibodies alone and in combination with factor concentrates (FVIII or FIX) or bypassing agents (rFVIIa, aPCC).
At time of sample analysis (single visit; Day 0)
Secondary Outcomes (4)
Analytical Sensitivity of TGA to Anti-TFPI Antibodies
Day 0
Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect
Day 0
Correlation Between TGA Parameters and Clinical Use of Anti-TFPI Therapies
Day 0
Detection of Hypercoagulability from Combined Therapy in TGA
Day 0
Study Arms (1)
Severe adult haemophilia A or B patient with factor levels ≤2%
* 6 on prophylaxis with FVIII or FIX concentrates after an adequate washout period of 48h for SHL FVIII molecules, at least 4 days for EHL-FVIII Fc and at least 10 days for EHL-FIX molecules * 5 receiving prophylaxis with marstacimab.
Interventions
One-time peripheral blood draw (10.8 mL total, 4 citrated tubes) collected during a routine clinical visit for thrombin generation testing on platelet-rich and platelet-poor plasma. No additional medical procedures or treatments are involved in the study.
Eligibility Criteria
Potentials patients for this study will be identified within the department of clinic hemostasis at Louis Pradel Hospital and Necker Hospital during their routine visit. Hemophila patients are coming regularly to the hospital for their consultaion and a blood drawn
You may qualify if:
- \- Male Patient
- years old
- severe hemophilia patients A or B (FVIII \< 1%,FIX\<=2%)
- on prophylaxis with FVIII or IX concentrates after an adequate washout period of 48h for SHL FVIII molecules, at least 4 days for EHL-FVIII Fc and at least 10 days for EHL-FIX molecules.
- On prophylaxis with Marstacimab
- Willing to participate
- Capable of following protocol procedures under investigator appreciation
You may not qualify if:
- \- patients refusing to provide 4 additional blood tubes for research
- Patient with an other coagulation disorder
- patients who received an injection of FVIII or FIX during the required washout period
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Groupement hospitalier Est Hôpital Cardilogique Service d'hémostase clinique
Bron, 69677, France
Centre de Référence Hémophilie et autres déficits rares en protéine de la coagulationCentre de Traitemendes Hémophiles F. Josso
Paris, 75015, France
Biospecimen
The specific types of samples that will be retained include platelet-rich plasma (PRP) and platelet-poor plasma (PPP) derived from citrated whole blood. During a routine visit, four citrate tubes of 2.7 mL each (totaling 10.8 mL) will be collected per patient. PRP is prepared by centrifugation at 150 × g for 10 minutes at 18°C within 30 minutes of collection. The plasma is carefully transferred to avoid leukocyte contamination and adjusted to a standardized platelet count if necessary. These samples will be used for thrombin generation testing, specifically via the Calibrated Automated Thrombogram (CAT) method, and will not be stored for long-term use-no long-term storage is planned.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2025
First Posted
August 3, 2025
Study Start
October 23, 2025
Primary Completion (Estimated)
August 1, 2026
Study Completion (Estimated)
August 1, 2026
Last Updated
March 23, 2026
Record last verified: 2026-03