Monitoring of Anti-TFPI in Hemophilia

Not yet recruiting

• Conditions: Hemophilia; Rebalancing Agents; Prophylaxis
• Interventions: Biological: blood sampling

• Registration Number: NCT07101926
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-28
• Study First Submitted QC: 2025-07-28
• Last Update Submitted: 2025-07-28
• Study Start: 2025-08-01
• Study First Posted: 2025-08-03
• Last Update Posted: 2025-08-03
• Primary Completion: 2026-08
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Severe adult haemophilia A or B patient with factor levels ≤2%	blood sampling	* 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.

Primary Outcome Measures

Name	Time	Method
Development of a Laboratory Assay to Assess Hemostatic Efficacy of Anti-TFPI Antibodies	At time of sample analysis (single visit; Day 0)	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).

Secondary Outcome Measures

Name	Time	Method
Analytical Sensitivity of TGA to Anti-TFPI Antibodies	Day 0	Evaluate the effect of different TGA conditions (e.g., low TF concentration, use of PRP, CTI) to enhance sensitivity to anti-TFPI antibodies.
Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect	Day 0	Determine which parameters (e.g., thrombin peak, ETP, lag time, velocity, time to peak) best reflect the action of anti-TFPI antibodies under optimized assay conditions.
Correlation Between TGA Parameters and Clinical Use of Anti-TFPI Therapies	Day 0	Compare TGA results from 5 patients treated with marstacimab and 3 patients with concizumab to assess correlation with clinical treatment exposure.
Detection of Hypercoagulability from Combined Therapy in TGA	Day 0	In vitro testing of anti-TFPI antibodies in combination with FVIII, FIX, rFVIIa, or aPCC to assess risk of excessive thrombin generation.

Trial Locations

Locations (2)

Groupement hospitalier Est Hôpital Cardilogique Service d'hémostase clinique; 🇫🇷 Bron, France

Centre de Référence Hémophilie et autres déficits rares en protéine de la coagulationCentre de Traitemendes Hémophiles F. Josso; 🇫🇷 Paris, France