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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Biotest
Sponsor:
Collaborators:
ICON plc
Interlab
Phoenix Clinical Research
Information provided by (Responsible Party):
Biotest
ClinicalTrials.gov Identifier:
NCT02065882
First received: February 3, 2014
Last updated: June 2, 2016
Last verified: June 2016
  Purpose
The purpose of the study is to investigate pharmacokinetics, efficacy and safety of BT524 in patients with congenital fibrinogen deficiency.

Condition Intervention Phase
Congenital Afibrinogenemia
Congenital Hypofibrinogenemia
Biological: BT524 (fibrinogen concentrate from human plasma)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biotest:

Primary Outcome Measures:
  • Terminal Elimination Half-life (t1/2) for fibrinogen antigen, [ Time Frame: Prior to the initial dose on day 1, at the end of the infusion and 0.5, 1, 2, 4, 8 hours post dose, 24, 48,96, 168, 240h and 336 hours post-dose ] [ Designated as safety issue: No ]
    The primary objective of this study is to investigate the 14 day single-dose pharmacokinetics of BT524 following intravenous (IV) infusion in patients with congenital afibrinogenemia or severe congenital hypofibrinogenemia (part I).


Secondary Outcome Measures:
  • Terminal Elimination Half-life (t1/2) for fibrinogen activity [ Time Frame: Prior to the initial dose on day 1, at the end of the infusion and 0.5, 1, 2, 4, 8 hours post dose, 24, 48,96, 168, 240 and 336 hours post-dose ] [ Designated as safety issue: No ]
    Secondary objectives are to investigate the 14 day single-dose pharmacodynamics of BT524, and the surrogate efficacy and safety of BT524 in part I of the study. In addition, the hemostatic efficacy, surrogate efficacy, and safety of single and/or repetitive administrations for on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) of bleeding events will be investigated.


Estimated Enrollment: 35
Study Start Date: March 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BT524
Single intravenous infusion of a fixed dose of 70 mg BT524 per kilogram body weight (BW)
Biological: BT524 (fibrinogen concentrate from human plasma)
single intravenous infusion

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.
  Eligibility

Ages Eligible for Study:   6 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 6 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
  • 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 below 22 kg
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02065882

Contacts
Contact: Judith Wessels-Kranz, PhD +49 6103 801 6395 judith_wessels@biotest.de
Contact: Andrea Wartenberg-Demand, MD +49 6103 801 497 wartenberg-demand@biotest.de

Locations
Egypt
Site 11 Recruiting
Cairo, Egypt
Germany
Site 07 Not yet recruiting
Gießen, Germany
Italy
Site 04 Not yet recruiting
Avellino, Italy
Site 03 Not yet recruiting
Milan, Italy
Site 05 Not yet recruiting
Padua, Italy
Site 06 Not yet recruiting
Palermo, Italy
Lebanon
Site 01 Recruiting
Beirut, Lebanon
Site 02 Not yet recruiting
Beirut, Lebanon
Tunisia
Site12 Recruiting
Tunis, Tunisia
Sponsors and Collaborators
Biotest
ICON plc
Interlab
Phoenix Clinical Research
Investigators
Principal Investigator: Claudia Djambas Khayat, MD Hôtel Dieu de France, Dept. of Pediatrics
  More Information

Responsible Party: Biotest
ClinicalTrials.gov Identifier: NCT02065882     History of Changes
Other Study ID Numbers: Biotest 984  2011-004154-25 
Study First Received: February 3, 2014
Last Updated: June 2, 2016
Health Authority: Lebanon: Ministry of Public Health
Italy: National Institute of Health
Germany: Paul-Ehrlich-Institut
Egypt: Ministry of Health and Population
Tunisia: Ministry of Public Health

Keywords provided by Biotest:
fibrinogen, bleeding,

Additional relevant MeSH terms:
Afibrinogenemia
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 28, 2016