Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study (GLAT)

University Hospital of Bordeaux

Status: Completed

Conditions: Glanzmann Thrombasthenia

Treatments: Other: Clot formation in whole blood under flow in a microfluidic flow chamber coated with tissue factor and collagen; Other: Concizumab; Other: Thrombin Generation Assay (TGA) in PRP using TF trigger; Other: : PRP viscoelastic changes under clot formation measured by thromboelastometry using RoTEM; Other: Global fibrinolytic capacity in PRP using reagents for in vitro triggering of the clot and its lysis

Study type: Interventional

Funder types: Other

Identifiers

NCT06234813

CHUBX 2021/44

Details and patient eligibility

About

Glanzmann thrombasthenia is a rare genetic disorder caused by the absence or the dysfunction of the main receptor present on the surface of platelets, integrin αIIbβ3 or GPIIb-IIIa.

The lack of this protein on the surface of platelets no longer allows these blood cells to bind to each other. This binding corresponds to the process of platelet aggregation.

Generally, local measures will control nasal and superficial bleeding whereas platelet transfusions are used to control or prevent life-threatening.

The main complication of this treatment is the risk of developing anti-αIIbβ3 antibodies directed against the absent protein and platelet transfusion therapy can become ineffective.

Activated recombinant factor VII (rFVIIa) provides an alternative treatment for GT patients who develop such antibodies. However, this therapy has a short duration of efficacy, requiring repeated intravenous administrations every 2 to 3 hours.

There is a new treatment, Concizumab, which has not yet been marketed. This treatment acts on TFPI (tissue factor pathway inhibitor). TFPI is a protein that occurs naturally in the body and prevents blood cells from binding to each other.

Concizumab works by blocking TFPI, which may allow sufficient clotting to prevent bleeding.

This treatment could replace recombinant activated factor VII (rFVIIa) because it has the advantage of a much longer duration of efficacy (about 3 days) and is administered subcutaneously.

Full description

This is in vitro research. The treatment will be tested on blood samples. This will allow us to evaluate in vitro the ability of Concizumab to restore coagulation compared to the usual treatments of platelet transfusions and recombinant activated factor VII (rFVIIa).

This is a single-center study conducted at the Bordeaux University Hospital, which included 10 with Glanzmann thrombasthenia patients and 10 healthy donors over a period of 12 months.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Glanzmann Thrombasthenia Group:

• Patient ≥18 years old
• Patient with a clear diagnosis of Glanzmann Thrombasthenia (GT), whatever the subtype of disease
• Affiliated person or beneficiary of a social security scheme.
• Free, informed and written consent signed by the participant, and the investigator (at the latest on the day of inclusion and before any examination required by the research)

Control Group:

• Healthy donor ≥ 18 years old
• Healthy donor, without haemorrhagic ant thrombotic medical history
• Person should not work in the investigator's department.
• Affiliated person or beneficiary of a social security scheme
• Free, informed and written consent signed by the participant, and the investigator (at the latest on the day of inclusion and before any examination required by the research)

Exclusion criteria

For both patient groups:

• Patient who has taken aspirin or a nonsteroidal anti-inflammatory medication within the previous 10 days
• Patient who has received a platelet transfusion or recombinant activated factor VII hemostatic treatment within the previous 7 days
• Patient who participated in another interventional study involving a drug within 30 days of entering this protocol
• Psychiatric, social or behavioral condition judged to be non-compatible with the respect of the protocol
• Adult protected by the law

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Glanzmann Thrombasthenia Group

Experimental group

Description:

Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease

Treatment:

Other: Global fibrinolytic capacity in PRP using reagents for in vitro triggering of the clot and its lysis

Other: : PRP viscoelastic changes under clot formation measured by thromboelastometry using RoTEM

Other: Concizumab

Other: Thrombin Generation Assay (TGA) in PRP using TF trigger

Other: Clot formation in whole blood under flow in a microfluidic flow chamber coated with tissue factor and collagen

Healthy donors

Active Comparator group

Description:

Healthy donor without haemorrhagic ant thrombotic medical history

Treatment:

Other: Global fibrinolytic capacity in PRP using reagents for in vitro triggering of the clot and its lysis

Other: : PRP viscoelastic changes under clot formation measured by thromboelastometry using RoTEM

Other: Thrombin Generation Assay (TGA) in PRP using TF trigger

Other: Clot formation in whole blood under flow in a microfluidic flow chamber coated with tissue factor and collagen