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

Brief Title

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

Official Title

A Prospective, Open-label, Phase I/III Study Investigating Pharmacokinetic Properties of BT524 and Efficacy and Safety of BT524 in the Treatment and Prophylaxis of Bleeding in Patients With Congenital Fibrinogen Deficiency

Brief Summary

      The purpose of the study is to investigate pharmacokinetics, efficacy and safety of BT524 in
      patients with congenital fibrinogen deficiency.
    

Detailed Description

      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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Terminal Elimination Half-life (t1/2) for fibrinogen antigen,

Secondary Outcome

 Terminal Elimination Half-life (t1/2) for fibrinogen activity

Condition

Congenital Afibrinogenemia

Intervention

BT524 (fibrinogen concentrate from human plasma)

Study Arms / Comparison Groups

 BT524
Description:  Single intravenous infusion of a fixed dose of 70 mg BT524 per kilogram body weight (BW)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

36

Start Date

March 2013

Completion Date

November 2020

Primary Completion Date

March 2020

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
      

Gender

All

Ages

N/A - 75 Years

Accepts Healthy Volunteers

No

Contacts

Claudia Djambas Khayat, MD, +49 6103 801, [email protected]

Location Countries

Egypt

Location Countries

Egypt

Administrative Informations


NCT ID

NCT02065882

Organization ID

Biotest 984

Secondary IDs

2011-004154-25

Responsible Party

Sponsor

Study Sponsor

Biotest

Collaborators

 ICON plc

Study Sponsor

Claudia Djambas Khayat, MD, Principal Investigator, Hôtel Dieu de France, Dept. of Pediatrics


Verification Date

July 2019