Essentials A novel
fibrinogen concentrate was evaluated in patients with congenital
fibrinogen deficiency. An open-label, phase 2-3 trial studied pharmacology, efficacy, and safety in patients >6 years. The product offers safe and effective
therapy in the treatment and prophylaxis of
bleeding. Data in recovery show the need of adjusted treatment and further investigation in children. SUMMARY: Background Single-factor replacement
therapy is considered the most suitable treatment option for hereditary
fibrinogen deficiency. A triple-secured plasma-derived human
fibrinogen product was developed to increase the safety of the former
fibrinogen concentrate. Objectives This non-randomized, open-label, prospective study investigated pharmacokinetics, efficacy, and safety of a novel
fibrinogen concentrate (FibCLOT® /CLOTTAFACT® LFB, France) in inherited deficiency. Patients/Methods Fourteen patients ≥40 kg received
fibrinogen concentrate for pharmacology and 16 ≥ 23 kg received treatment for
bleeding or surgery. Each treatment was followed by a 3-week safety observation period. Key outcomes included number of infusions, dose,
bleeding control, daily assessment,
hemoglobin, blood loss, transfusions, and physicians' global assessment of response. Results Incremental recovery was 2.35 mg mL-1 per mg kg-1 and maximal concentration 1.41 g L-1 (geometric mean) after 0.060 g kg-1 infusion in 14 afibrinogenemic patients. Terminal half-life was 69.3 h (non-compartmental analysis). The maximum clot firmness was increased by a mean of 10.3 mm from baseline to maximal effect. Sixteen patients participated to the efficacy phase: 32
bleeding episodes were treated in 9 patients, and 15 patients underwent 38 surgical/invasive procedures. All patients achieved appropriate hemostasis: response to treatment was successful in all bleeds (95% CI, 0.89-1.00) and procedures (95% CI, 0.91-1.00). Most (94%) bleeds were controlled with a single infusion (median 0.050 g kg-1 ). Two patients experienced asymptomatic distal
venous thromboses identified by systematic ultrasound. Conclusion FibCLOT® /CLOTTAFACT® showed a pharmacokinetic profile comparable to that of other
fibrinogen concentrates and provides safe and clinically effective substitution
therapy for
fibrinogen-deficient patients.