pharmacokinetic, efficacy and safety of bt524 in patients with congenital fibrinogen deficiency

Conditions: Congenital Afibrinogenemia; Congenital Hypofibrinogenemia

Summary: the purpose of the study is to investigate pharmacokinetics, efficacy and safety of bt524 in patients with congenital fibrinogen deficiency.

the present study is designed as a prospective, open-label, multicentre, phase i/iii study investigating the 14 day single-dose pharmacokinetic properties, efficacy and safety of bt524 following intravenous administration in the treatment or prophylaxis of bleeding in patients with congenital afibrinogenemia or severe congenital hypofibrinogenemia.

Eligibility criteria:
inclusion criteria: * known congenital afibrinogenemia or severe congenital hypofibrinogenemia * plasma fibrinogen activity ≤ 0.5 g/l and antigen ≤ 0.5 g/l * male or female * age 0 to 75 years, with the first ten patients will be 18 years or * presumed to be compliant with the study procedures and to terminate the study as scheduled * willing and able to be hospitalized for 3 days for the pharmacokinetic assessment (if applicable) * willing and able to be hospitalized - if required - in case of interventions (e.g., surgical procedures, major bleeds) * written informed consent by the patient, his/her parents or by the patient's legal / authorized representative as applicable exclusion criteria: * known congenital dysfibrinogenemia * known bleeding disorder other than congenital fibrinogen deficiency * history of esophageal variceal bleeding * known presence or history of venous/arterial thrombosis or thromboembolic event in the preceding 6 months * known presence or history of fibrinogen inhibitory antibodies * known presence or history of hypersensitivity to human fibrinogen or human plasma proteins e.g., immunoglobulins, vaccines or hypersensitivity to any of the excipients * known positive serology for hiv-1 and hiv-2 * clinically relevant biochemical or hematological findings (except due to underlying disease or emergency bleeding) outside the normal range (at the investigator's discretion) * clinically relevant pathological findings in physical examination including electrocardiogram (ecg) * treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 2 weeks prior to infusion of bt524 * concomitant medication interacting relevantly with the coagulation system (e.g., low molecular weight heparin, unfractioned heparin, factor xa inhibitors, factor iia inhibitors or py12 inhibitors) within 2 weeks prior to infusion of bt524 * recent vaccination (within 3 weeks prior to infusion) * body weight (bw) below 22 kg for patients ≥ 6 years; bw below the 5th percentile of the normal range for children \< 6 years (refers to local standard) * end stage disease * abuse of drugs * unable to understand and follow the study requirements * participation in another interventional clinical study within 30 days before entering the study or during the study * pregnant/ nursing woman, or woman of childbearing potential not using reliable/ effective contraceptive method(s) during the study and at least one month after the last administration of study drug (e.g., oral/ injectable/ implantable/ insertable/ topical hormonal contraceptives, intrauterine devices, female sterilization, partner's vasectomy or condoms) * any other condition that, to the investigator's judgment, could have an impact on patient's safety or the study results * elective surgery during the 14 day pk blood sampling period * acute infection * clinically relevant increase or decrease in body temperature * actively bleeding or anticipated bleeding (including female menorrhea) at the time point of or within 7 days prior to infusion of bt524 * surgery within 7 days prior to infusion of bt524 * immobilization within 7 days prior to infusion of bt524 * intake of alcohol or significantly increased intake of caffeine containing products within 24 hours prior to infusion of bt524 * blood donation or comparable blood loss within 60 days prior to infusion of bt524 * excessive physical exercise (extreme sports activities, sauna) within 72 hours prior to infusion of bt524

Keywords: fibrinogen, bleeding,