Clinical trial NCT06234813: Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study
Official title: Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glanzmann Thrombasthenia
Keywords: Concizumab
Hemostatic capacity
Glanzmann Thrombasthenia
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2024-01-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effects of mixing concizumab compared with the main bleed treatment options for persons with GT
timeFrame: One point at the inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux - Laboratoire Hématologie
Study officials:
affiliation: University Hospital, Bordeaux
name: Mathieu FIORE
role: PRINCIPAL_INVESTIGATOR
References: