Thromb Haemost 2020; 120(06): 957-967
DOI: 10.1055/s-0040-1710015
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Pharmacology, Efficacy and Safety of a Triple-Secured Fibrinogen Concentrate in Children Less than or Equal to 12 Years with Afibrinogenaemia

Claudia Djambas Khayat
1  Department of Pediatrics, Hotel-Dieu de France Hospital, Beirut, Lebanon
,
Mohamed El Khorassani
2  Children's Hospital, Mohammed V. University, Rabat, Morocco
,
Selin Aytaç
3  Department of Pediatric Haematology, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children's Hospital, Ankara, Turkey
,
Annie Harroche
4  Haemophilia Care Centre, Necker Hospital, Paris, France
,
Amel Dahmane
5  Clinical Development, Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, France
,
Sonia Pujol
5  Clinical Development, Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, France
,
5  Clinical Development, Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, France
,
Philippe de Moerloose
6  Division of Angiology and Hemostasis, Faculty of Medicine, Geneva, Switzerland
,
Françoise Bridey
5  Clinical Development, Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, France
› Author Affiliations
Funding LFB (Les Ulis, France) sponsored the clinical study presented in this paper.
Further Information

Publication History

20 January 2020

23 March 2020

Publication Date:
11 May 2020 (online)

Abstract

Objective To date, the use of a fibrinogen concentrate (FC) administered in children with inherited fibrinogen deficiency is poorly documented. Treatment modalities may differ from those of adults. The aim of this study was to investigate the pharmacokinetics (PK), efficacy (bleeding/surgery) and safety of a triple-secured FC (FibCLOT, LFB, France) in young patients aged of 12 years or less.

Methods This was a prospective, non-comparative, multicentre, phase 2–3 study. Estimated PK parameters were based on population PK modelling. Target fibrinogen levels were 1.2 and 1.0 g/L for major and minor events, respectively. In vivo recovery (IVR) was calculated at study entry to tailor the dose.

Results Sixteen afibrinogenaemia patients were treated with FC: 12 included in the PK study (6 aged ≤ 6 years and 6 aged 7–12 years). IVR at 1 hour post-infusion (geometric mean [coefficient of variation]) was 1.91 [20%] mg/dL per mg/kg and results were similar between the two age groups (1.87 [14%]) and (1.96 [27%]) with no statistical differences. Estimated half-life (t 1/2) was 49.0 hours [12%] with no observed differences between groups (46.6 hours [10%] and 51.6 hours [12%]). Overall efficacy was rated as excellent/good in 96.9% of 32 bleeds and in 100% of 11 surgeries. Most of the events (39/43, 90.7%) were managed with one infusion. There was no serious adverse drug reaction.

Conclusion Individually tailored dosing was efficacious in children who exhibited a lower IVR and shorter t 1/2 than those previously reported in adolescent and adult patients emphasising the importance of individualised dose optimisation.

Authors' Contributions

C.D.K., M.E.K. and S.A. conducted the study, contributed to patient enrolment and collected the data. A.D. was clinical trial manager, S.P. and C.H. contributed to the analysis of data and edited the manuscript. F.B. conducted the analysis, assessed the literature and wrote the manuscript. P.d.M. supervised the manuscript. All authors reviewed and approved the final manuscript.