Patients with congenital afibrinogenemia or severe congenital hypofibrinogenemia. MedDRA version: 14.1 Level: PT Classification code 10016075 Term: Factor I deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Fibrinogen Concentrate from Human Plasma
Product Code: BT524
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Human Fibrinogen Concentrate
CAS Number:
Sponsors
Biotest AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Congenital afibrinogenemia or severe congenital hypofibrinogenemia defined by plasma fibrinogen activity = 0.5 g/l and antigen = 0.5 g/l 2.Male or female 3.Age 6 to 75 years, with the first ten patients will be 18 years or older 4.Presumed to be compliant with the study procedures and to terminate the study as scheduled 5.Willing and able to be hospitalized for 3 days for the pharmaco-kinetic assessment 6.Willing and able to be hospitalized - if required - in case of interventions (e.g., surgical procedures, major bleeds) 7.Written informed consent by the patient, his/her parents or by the patient's legal / authorized representative as applicable Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: General exclusion criteria: 1.Known congenital dysfibrinogenemia 2.Known bleeding disorder other than congenital fibrinogen deficiency 3.History of esophageal variceal bleeding 4.Known presence or history of venous/arterial thrombosis or thromboembolic event in the preceding 6 months 5.Known presence or history of fibrinogen inhibitory antibodies 6.Known presence or history of hypersensitivity to human fibrinogen or human plasma proteins e.g., immunoglobulins, vaccines 7.Known positive serology for HIV-1 and HIV-2 8.Clinically relevant biochemical or hematological findings (except due to underlying disease or emergency bleeding) outside the normal range (at the investigator's discretion) 9.Clinically relevant pathological findings in physical examination including electrocardiogram (ECG) 10.Treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 2 weeks prior to infusion of BT524 11.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 12.Recent vaccination (at least 3 weeks) 13.Body weight below 22 kg 14.End stage disease 15.Abuse of drugs 16.Unable to understand and follow the study requirements 17.Participation in another interventional clinical study within 30 days before entering the study or during the study 18.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) 19.Any other condition that, to the investigator's judgment, could have an impact on patient's safety or the study results PK-specific exclusion criteria: 20.Elective surgery during the 14 day PK blood sampling period 21.Acute infection 22.Clinically relevant increase or decrease in body temperature 23.Actively bleeding or anticipated bleeding (including female menorrhea) at the time point of or within 7 days prior to infusion of BT524 24.Surgery within 7 days prior to infusion of BT524 25.Immobilization within 7 days prior to infusion of BT524 26.Intake of alcohol or significantly increased intake of caffeine containing products within 24 hours prior to infusion of BT524 27.Blood donation or comparable blood loss within 60 days prior to infusion of BT524 28.Excessive physical exercise (extreme sports activities, sauna) within 72 hours prior to infusion of BT524
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the 14 day single-dose pharmacokinetics of BT524 following intravenous infusion in patients with congenital fibrinogen deficiency (afibrinogenemia or severe hypofibrinogenemia).;Secondary Objective: To investigate the 14 day single-dose pharmacodynamics, the surrogate efficacy and safety of the single intravenous infusion of BT524. To investigate efficacy, surrogate efficacy and safety, of single and/or repetitive intravenous infusions of BT524 for on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) of bleeding events. ;Primary end point(s): Pharmacokinetics Single-dose pharmacokinetics of fibrinogen antigen will be assessed by the following variables: •Terminal Elimination Half-life (t1/2) for fibrinogen antigen •Time to reach Maximum Concentration (tmax) •Maximum Concentration (Cmax) •Area Under the Concentration-Time Curve (AUC) calculated to the last measured concentration (AUC(0-t)) and extrapolated to infinity (AUC(0-inf) •Clearance (CL) •Mean Residence Time (MRT) •Volume of Distribution (Vss) •Incremental Recovery (IR) •Classical in vivo Recovery (IVR) ;Timepoint(s) of evaluation of this end point: After a single intravenous infusion pharmacokinetics will be assessed for 14 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamics Single-dose pharmacodynamics of fibrinogen activity will be assessed by the following variables: •Terminal Elimination Half-life (t1/2) for fibrinogen activity •Time to reach Maximum Concentration (tmax) •Maximum Concentration (Cmax) •Area Under the Concentration-Time Curve (AUC) calculated to the last measured concentration (AUC(0-t)) and extrapolated to infinity (AUC(0-inf) •Clearance (CL) •Mean Residence Time (MRT) •Volume of Distribution (Vss) Incremental •Recovery (IR) Classical in vivo Recovery (IVR) Surrogate Efficacy Maximum clot firmness (MCF, mm) measured by rotational thromboelastometry Part I -Comparison of MCF pre-dose and at 1 and 8 hours post-end of IV infusion --Correlation between MCF and fibrinogen activity pre-dose and at 1 and 8 hours post-end of IV infusion Part II -Comparison of MCF pre-dose and at 1 hour post-end of each IV infusion -Correlation between MCF and fibrinogen activity pre-dose and at 1 hour post-end of each IV infusion Clinical Efficacy The following efficacy parameters will be assessed after each bleeding event: •Overall hemostatic response to treatment with BT524 for each surgical procedure and each major bleed as assessed by the investigator according to a 4 point scale: "none", "moderate", "good" or "excellent" •Total loss of blood (e.g., intra- and postoperatively, re-bleedings), if applicable •Units of other fibrinogen-containing products infused besides BT524 e.g., fresh frozen plasma or cryoprecipitate •Units of transfusion products infused e.g., allogenic or autologous blood (packed red blood cells, fresh whole blood), platelets •Consumption of BT524 (dose per kilogram body weight required pre-, intra- or post-operatively for effective treatment) The following efficacy parameter will be assessed after wound healing is expected to be resolved •Quality of wound healing, if applicable Safety •Electrocardiogram •Adverse events •Devel | — |
Countries
Egypt, Germany, Italy, Lebanon
Contacts
Public ContactCorporate Clinical Research
Biotest AG
Outcome results
None listed