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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2715-2994
Coagulation and Fibrinolysis

Pharmacokinetics, Hemostatic Efficacy, and Safety of a New Human Fibrinogen Concentrate in Adult and Pediatric Patients with Congenital Fibrinogen Deficiency

Authors

  • Claudia Djambas Khayat

    1   Department of Pediatrics, Hotel Dieu de France Hospital Beirut, Saint Joseph University, Lebanon

  • Amal El-Beshlawy

    2   Pediatric Hospital CU, Egyptian Thalassemia Association, El Cairo, Egypt

  • Balkis Meddeb

    3   Hospital Aziza Othmana, Tunis, Tunisia

  • Abderrahim Khelif

    4   Hospital Farhat Hached, Faculte de Medecine Ibn El Jazzar, Sousse University, Tunisia

  • Wolfgang Miesbach 

    5   Department of Haemostasis/Haemophilia Centre, Medical Clinic 2, University Hospital Frankfurt, Frankfurt, Germany

  • Sonia Adolf

    6   National Research Center, Pediatric Hematology Department, El Cairo, Egypt

  • Heike Boehm

    7   Biotest AG, Dreieich, Germany

  • Silke Aigner

    7   Biotest AG, Dreieich, Germany

  • Salomon Abraha

    7   Biotest AG, Dreieich, Germany

  • Fabian Bohlaender

    7   Biotest AG, Dreieich, Germany

  • Joerg Schuettrumpf

    7   Biotest AG, Dreieich, Germany
    8   Grifols, Barcelona, Spain

Funding Information This work was supported by Biotest AG, manufacturer of the human fibrinogen concentrate, BT524.
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ABSTRACT

Background

Congenital fibrinogen deficiencies are rare coagulopathies which are treated by fibrinogen concentrates. This trial investigated the pharmacokinetic/pharmacodynamic (PK/PD) parameters, and surrogate efficacy and safety of a new human fibrinogen concentrate (HFC), BT524, in patients with congenital afibrinogenemia or severe hypofibrinogenemia.

Methods

This prospective, multi-national, open-label, single-arm PK/PD trial evaluated PK/PD parameters of HFC (part 1; phase I) and HFC as on-demand treatment or prophylaxis for bleeding events (part 2; phase III). In part 1, patients received a single-dose of HFC (70 mg/kg body weight [BW]). PK/PD parameters were calculated using a PK/PD model and non-compartmental analysis. Fibrinogen antigen (FiAg) levels were determined over 14 days by immunonephelometry and fibrinogen activity (FiAc) by Clauss assay. The efficacy variable was mean change in maximum clot firmness (MCF) analyzed by thromboelastometry. Safety parameters were evaluated for 49 days.

Results

A total of 27 patients (n = 15 adults, n = 12 children) were treated with HFC. For FiAg, mean (SD) PK parameters were: Cmax 1.81 (0.42) g/L, AUC0-∞ 173 (45.4) g*h/L, and t1/2 67.9 (15.3) h. For FiAc, they were Cmax 1.26 (0.4) g/L, AUC0-∞ 104 (33.5) g*h/L, and t1/2 60.3 (13.3) h. In adults, MCF significantly increased 1 h after HFC infusion (11.1 (5.1) mm; P < 0.0001; 95% CI: 9.33–14.47). In pediatrics, mean increase in range was 9.3 to 16.5 mm. Treatment-related adverse events were rare, with one mild increase in fibrin D-dimer. No thromboembolic events, hypersensitivity, or allergic reactions were observed.

Conclusion

HFC effectively increased FiAg levels and FiAc, improved clot firmness, and showed a favorable safety and tolerability profile in adult and pediatric patients with congenital fibrinogen deficiency.

Keywords

afibrinogenemia - hypofibrinogenemia - congenital fibrinogen deficiency - fibrinogen concentrate - pharmacokinetics

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.


Contributors' Statement

C.D.K., A.El-B., B.M., A.Kh., D.K., W.M., and S.A.: data collection, investigation, writing—review and editing; H.B., S.Ai., S.A., F.B., and J.S.: conceptualization, methodology, data curation, writing—review and editing. All authors critically revised, edited, and approved the final manuscript.


Clinical Trial Registration

The trial is registered at the US National Institute of Health (clinicaltrials.gov) NCT02065882.


Supplementary Material



Publikationsverlauf

Eingereicht: 30. April 2025

Angenommen: 19. September 2025

Artikel online veröffentlicht:
17. Oktober 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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