In Vitro Correction of Thrombin Generation by Concizumab (Anti-TFPI) for Severe Hemophilia Patients

Hemophilia Clinical Trial

Official title:

Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05617209
• Other study ID #: 21CH036
• Status: Recruiting
• Start date: September 7, 2021
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: Brigitte Tardy-, MD
• Phone: (0)477828591
• Email: brigitte.tardy[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Studies have shown, in haemophilia patients, the effectiveness of Anti TFPI antibody (aTFPIAb) to prevent joint and muscular bleeding (tissues poor in Tissue Factor (TF)). However, cases of cerebral thrombosis (tissues rich in TF) have been observed in some patients treated with this antibody. Because an inter-individual variation in thrombin generation correction by aTFPIAb, an aTFPIAb concentration effective at low TF concentration could be at the same time thrombogenic at high TF concentration.

Description:

The aim of this study is to determine, for each patient, the minimum concentration of aTFPIAb necessary to restore thrombin generation in the presence of low (1pM) TF concentration and to evaluate at this concentration of aTFPIAb a potential thrombogenic effect in the presence of a high (10pM) TF concentration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Severe or moderate haemophilia A or B patient with FVIII or FIX <5% with or without prophylaxis

• Affiliated or beneficiary of a social security regimen

• Signature of consent

Exclusion Criteria:

• Haemophilia patients aged 12 years or less with a weight less than 30 kg (taking into account the volume of blood collection).

• Patients who received factor VIII concentrates less than 48 hours or factor IX concentrates less than 96 hours prior to the routine blood draw at the Hemophilia Clinic. 96 hours prior to the routine blood draw at the Hemophilia Centre

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Other:
• thrombin generation measurement
Thrombin generation will be measured in Platelets rich plasma induced either by 1 pM TF or 10 pM TF concentration in presence of different aTFPIAb concentrations (0; 0.5 µg/ml; 0.75 µg/ml; 1.0 µg/ml; 2.0 µg/ml; 4.0 µg/ml)

Locations

Country	Name	City	State
France	CHU Saint-Etienne	Saint-Etienne

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	minimum concentration of anti-TFPI antibody	Determine the minimum concentration of anti-TFPI antibody (µg/ml) that normalizes the peak to 1 pM FT	day 1
Secondary	Measurement of the clot structure	Measurement of the clot structure (density fibers in g/cm3) by scanning electron microscopy	day 1