Monitoring of Anti-TFPI in Hemophilia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorHospices Civils de Lyon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
- Male Patient
18 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.
Disqualifiers
- 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
Trial population
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
Trial design
Design model
Case-only
Time perspective
Prospective
Treatments tested in this trial
blood sampling
Biological/VaccineOne-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.
Treatment groups
11 Participants
are divided into 1 treatment groupGroup A: Severe adult haemophilia A or B patient with factor levels ≤2%1 intervention
Trial outcomes
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).
Time frame
At time of sample analysis (single visit; Day 0)Secondary outcomes
1
Analytical Sensitivity of TGA to Anti-TFPI Antibodies
Evaluate the effect of different TGA conditions (e.g., low TF concentration, use of PRP, CTI) to enhance sensitivity to anti-TFPI antibodies.
Time frame
Day 02
Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect
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.
Time frame
Day 03
Correlation Between TGA Parameters and Clinical Use of Anti-TFPI Therapies
Compare TGA results from 5 patients treated with marstacimab and 3 patients with concizumab to assess correlation with clinical treatment exposure.
Time frame
Day 04
Detection of Hypercoagulability from Combined Therapy in TGA
In vitro testing of anti-TFPI antibodies in combination with FVIII, FIX, rFVIIa, or aPCC to assess risk of excessive thrombin generation.
Time frame
Day 0Sponsors and contacts
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Source ClinicalTrials.gov