Pharmacokinetic, Efficacy and Safety of BT524 in Patients With Congenital Fibrinogen Deficiency

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 older
• 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 (not applicable for adult patients with hypodysfibrinogenemia in study part II)
• 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
• 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 such as: low molecular weight heparin or unfractioned heparin, factor Xa inhibitors, thrombin inhibitors (factor II a inhibitors), antiplatelet drugs (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 standards)
• 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