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NCT Number: NCT06234813

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

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.

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Key information

Conditions

Glanzmann Thrombasthenia Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Platelet Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Thrombasthenia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Bordeaux - Laboratoire Hématologie

Bordeaux, France

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Other

TTAS (single measurements)

Clot formation in whole blood under flow (2000 s-1) in a microfluidic flow chamber coated with tissue factor and collagen (T-TAS with AR chip)

  • 500 µL of whole blood for each point;
  • 7 points for each condition;
  • Around 4 mL of whole blood will be needed for each patient or healthy subject;
  • Values for Area Under the Curve (Aritrary Unit), Occlusion Starting Time (min), Occlusion Time (min.) will be reported.

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

Other

ROTEM (single measurements)

  • ROTEM cups will be added
  • 20 µL calcium reagent (STARTEM)
  • 20 µL of 2,940-fold prediluted r-ExTEM reagent (50,000 fold dilution relative to 340 µL in the cup) added
  • 300 µL spiked PRP at 250 G/L (2.5 mL of PRP/patient)
  • Values for clot time (CT sec, clot formation time (CFT) sec, maximum clot formation (mm) will be reported.

Thrombin Generation Assay (TGA) in PRP using TF trigger

Other

TGA (single measurements)

  • The following will be added to well:
  • 20 uL of PRP-Reagent
  • 80 uL of spiked PRP (600 µL/patient at 100 G/L)
  • 20 uL FluCa
  • Values for thrombin activity versus time and the derived parameters incl. lag-time (min), time to peak (min), time to peak (min), ETP (Arbitrary Unit) will be reported.

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

Other

Global fibrinolytic capacity (Lysis Timer) in 100 µL of PRP (250 G/L) using reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA). Around 1 mL of PRP in total Lysis time in min

Concizumab

Other

Thrombin generation assay (TGA), microchip flow-chamber assay (T-TAS, rotational thromboelastometry and global fibrinolytic capacity to investigate and compare the effects of mixing concizumab (200, 1000 and 4000 ng/mL) with the main bleed treatment options for persons with GT

Primary outcomes

  1. Effects of mixing concizumab compared with the main bleed treatment options for persons with GT

    Time frame: One point at the inclusion

    The samples will be analysed by measurement of in vitro hemostatic capacity :

    • Clot formation in whole blood under flow (2000 s-1) in a microfluidic flow chamber coated with tissue factor and collagen. Values for Area Under the Curve (Aritrary Unit), Occlusion Starting Time (min), Occlusion Time (min.) will be reported
    • PRP viscoelastic changes under clot formation measured by thromboelastometry. Values for clot time (sec), clot formation time (sec), maximum clot formation (mm) will be reported
    • Thrombin Generation Assay in PRP using tissue factor trigger. Values for thrombin activity versus time and the derived parameters incl. lag-time (min.), time to peak (min), time to peak (min), ETP (Arbitrary Unit) will be reported
    • Global fibrinolytic capacity (Lysis Timer in min) in whole blood using reagents for in vitro triggering of the clot and its lysis

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Acronym: GLAT

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Jan 31, 2024
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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