A new clinical trial will investigate the minimum concentration of concizumab (anti-TFPI antibody [aTFPIAb]) required to provide beneficial therapeutic effects in the tissues of patients with severe hemophilia with low (1 pM) tissue factor (TF) concentrations and to evaluate the thrombogenic effects of the same dose in tissues rich (10 pM) in TF.
The prospective study aims to enroll 20 male participants with a confirmed diagnosis of hemophilia A or B and factor VIII or factor IX levels <5% with or without prophylaxis. All patients must be aged 12 to 65 years at the time of treatment initiation.
Due to the high volume of blood collection, the exclusion criteria include age of fewer than 12 years and body weight of less than 30 kg. 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 clinic will also be excluded.
At the end of the consultation and follow-up of the disease, the researchers will collect an additional 35-mL blood sample.
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The primary outcome measure of the study is the minimum concentration of aTFPIAb (µg/mL) that normalizes the peak to 1 pM TF. For this purpose, the researchers will analyze thrombin generation in platelet-rich plasma induced by either 1 pM or 10 pM TF concentration in the presence of different aTFPIAb concentrations (0, 0.5, 0.75, 1.0, 2.0, and 4.0 µg/mL). The study protocol also includes the measurement of the clot structure (density fibers in g/cm3) by scanning electron microscopy as the secondary outcome measure.
Concizumab has proven effective in preventing hemorrhage in tissues low in TF such as joints and muscles. However, observed cases of cerebral thrombosis in patients treated with the antibody raise concerns about its thrombogenic effects in tissues rich in TF.
In vitro correction of thrombin generation by concizumab (anti-TFPI) for severe hemophilia patients. ClinicalTrials.gov. November 15, 2022. Accessed December 13, 2022.