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Clinical pharmacology, efficacy and safety study of a triple‐secured fibrinogen concentrate in adults and adolescent patients with congenital fibrinogen deficiency
Author(s) -
Djambas Khayat Claudia,
El Khorassani Mohamed,
Lambert Thierry,
Gay Valérie,
BarthezToullec Malika,
Lamazure Jennifer,
Bellon Anne,
Henriet Céline,
Bridey Françoise,
Négrier Claude
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14392
Subject(s) - medicine , fibrinogen , blood product , clinical trial , pharmacokinetics , surgery , gastroenterology
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 (Fib CLOT ® / 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 Fib CLOT ® / CLOTTAFACT ® showed a pharmacokinetic profile comparable to that of other fibrinogen concentrates and provides safe and clinically effective substitution therapy for fibrinogen‐deficient patients.