Congenital AfibrinogenemiaPhase 3NCT02065882
Pharmacokinetic, Efficacy and Safety of BT524 in Patients With Congenital Fibrinogen Deficiency
A Phase 3 study testing BT524 (Part I) and BT524 (Part II) in people with Congenital Afibrinogenemia and Congenital Hypofibrinogenemia, run by Biotest at 6 sites in 5 countries.
Trial summary
This was a prospective, open-label, multicenter, phase I/III study investigating the 14-day single-dose pharmacokinetic and pharmacodynamic properties, efficacy and safety of BT524 following intravenous administration in the treatment or prophylaxis of bleeding in patients with congenital afibrinogenemia or severe… Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Congenital Afibrinogenemia, Congenital Hypofibrinogenemia
- What is being tested?
- BT524 (Part I) and BT524 (Part II)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Mar 2013to 18 Nov 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
About this study
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
This was a prospective, open-label, multicenter, phase I/III study investigating the 14-day single-dose pharmacokinetic and pharmacodynamic 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.
Read the detailed description
The study was divided into two parts (Part I and Part II). Part I focused on the primary endpoint of the study, 14-day single-dose pharmacokinetics (PK) and 14-day single-dose pharmacodynamics (PD), as well as the assessment of maximum clot firmness (MCF) as a surrogate parameter for efficacy. Part I of the study was followed by Part II, which evaluated the efficacy and safety of single and repetitive administration of BT524 in patients undergoing on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) for various bleeding events [e.g., elective surgery, spontaneous or post-traumatic major bleeding]. All patients who participated in the PK assessment (Part I) without severe post-administration complications ideally continued treatment with BT524 for ODP and/or ODT in Part II.
- Being tested
- BT524 (Part I), BT524 (Part II)
- Keywords
- fibrinogen, bleeding,
- Medical subject headings
- Afibrinogenemia, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BT524 (Part I)Drug
Also called Human Fibrinogen Concentrate
Single intravenous infusion of 70 mg BT524 per kg body weight.
BT524 (Part II)Drug
Also called Human Fibrinogen Concentrate
Single or repetitive intravenous infusion(s) of BT524, depending on the severity of the disorder, location and extent of the bleeding and patient's clinical condition. Dosage based on individual body weight and fibrinogen level.
| Study group | Role | What they receive |
|---|---|---|
| BT524 | Experimental | Part I: A single intravenous infusion of BT524 for assessment of PK/PD of BT524.
Part II: A single or repetitive intravenous infusion(s) of BT524 for on-demand prophylaxis/on-demand treatment of bleeding events. Receives: Drug: BT524 (Part I); Drug: BT524 (Part II) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Single-dose Pharmacokinetics (PK) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Antigen
T1/2 of fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. T1/2 was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacokinetics (PK) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Antigen
Time of occurence of Cmax relative to dosing (Tmax) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Tmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Maximum Concentration (Cmax) for Fibrinogen Antigen
Maximum observed plasma concentration (Cmax) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Cmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Antigen
AUC0-tz: Area under the time course of the plasma concentrations calculated from time zero up to the last quantifiable plasma concentration for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUC0-tz was derived from time-concentration profiles using adapted methodology (noncompartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Antigen
AUCextr: extent of AUC extrapolation beyond last concentration for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUCextr was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Antigen
AUC0-∞: AUC from time 0 to infinity for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUC0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Antigen
MRT0-∞: Mean Residence Time (MRT) extrapolated to infinity for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. MRT0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Clearance (CL) for Fibrinogen Antigen
CL: Total clearance (CL) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. CL was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Antigen
Vdss: Volume of distribution at presumed steady-state for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Vdss was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Antigen
Vdss per kg BW: Volume of distribution at presumed steady-state per kg bodyweight for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Vdss per kg BW was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Incremental Recovery (IR) for Fibrinogen Antigen
IR is the dose-adjusted maximum fibrinogen increase in plasma within 4 hours after the end of infusion.
Measured: Between pre-dose and 4 hours post-dose
Single-Dose Pharmacokinetics (PK) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Antigen
CIR: maximum fibrinogen increase in plasma within 4 hours after the end of infusion divided by the maximum theoretical fibrinogen increase
Measured: Between pre-dose and 4 hours post-dose
Secondary outcomes (16)
Single-dose Pharmacodynamics (PD) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Activity
T1/2 of fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. T1/2 was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Activity
Time of occurence of Cmax relative to dosing (Tmax) for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. Tmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Maximum Concentration (Cmax) for Fibrinogen Activity
Maximum observed plasma concentration (Cmax) for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. Cmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Activity
AUC0-tz: Area under the time course of the plasma concentrations calculated from time zero up to the last quantifiable plasma concentration for fibrinogen activity, was determined from samples taken at several time points during the 14 day sampling period. AUC0-tz was derived from time-concentration profiles using adapted methodology (noncompartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Activity
AUCextr: extent of AUC extrapolation beyond last concentration for fibrinogen activity, was determined from samples taken at several time points during the 14 day sampling period. AUCextr was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Activity
AUC0-∞: AUC from time 0 to infinity for fibrinogen activity, was determined from samples taken at several time points during the 14 day sampling period. AUC0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Activity
MRT0-∞: Mean Residence Time (MRT) extrapolated to infinity for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. MRT0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Clearance (CL) for Fibrinogen Activity
CL: Total clearance (CL) for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. CL was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Activity
Vdss: Volume of distribution at presumed steady-state for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. Vdss was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Activity
Vdss per kg BW: Volume of distribution at presumed steady-state per kg bodyweight for fibrinogen activity was determined from samples taken at several time points during the 14 day sampling period. Vdss per kg BW was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Measured: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Incremental Recovery (IR) for Fibrinogen Activity
IR is the dose-adjusted maximum fibrinogen increase in plasma within 4 hours after the end of infusion.
Measured: Between pre-dose and 4 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Activity
CIR: maximum fibrinogen increase in plasma within 4 hours after the end of infusion divided by the maximum theoretical fibrinogen increase
Measured: Between pre-dose and 4 hours post-dose
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion
Maximum Clot Firmness (MCF), assessed by rotational thromboelastometry (ROTEM), was used as a surrogate marker of haemostatic efficacy following administration of BT524. In Part I, MCF was measured before and 1 hour after the end of a single BT524 infusion. In Part II, MCF was measured before and 1 hour after the end of each BT524 infusion administered to treat bleeding events. The variable was the change in MCF from pre-dose to 1 hour post-end of infusion.
Measured: Part I: pre-dose and at 1 hour post-end of infusion. Part II: pre-dose and at 1 hour post-end of infusion of each bleeding event.
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II
Overall hemostatic response (OHR) to treatment with BT524 for each surgical procedure and each treated bleed was rated on a 4-point scale ("none", "moderate", "good" or "excellent"). The sum of good and excellent ratings was defined as "success" in the analysis. Frequencies and percentages of OHR on event level (Success rate in % = number of successfully treated bleeding events / total number of bleeding events).
Measured: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II
Total loss of blood was rated by the investigator per surgical bleeding events (eg, intra- and post-operatively, rebleedings) using the classifications of "lower than expected", "within the expected range", and "higher than expected". The ratings were analyzed descriptively (frequencies and percentages) on event level for the Full Bleeding Event Set (FBE).
Measured: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Clinical Efficacy for BT524: Units of Other Fibrinogen-containing Products (FCP) Infused Besides BT524 in Study Part II
Units of other fibrinogen-containing products (FCP) infused besides BT524 eg, fresh frozen plasma (FFP) or cryoprecipitate or alternative commercially available fibrinogen concentrates given to counteract hemodynamic instability were documented and analyzed descriptively on event level for the FBE.
Measured: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startMar 2013
- Primary completion18 May 2020
- Study completion18 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital AfibrinogenemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The study was divided into two parts: PK/PD Part I and Efficacy Part II. Patients eligible for PK/PD Part I received a fixed dose of 70 mg BT524 per kilogram body weight (BW) via a single intravenous infusion. Part I was followed by Part II. In Part II, patients received a variable, individually tailored dose of BT524 for on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) in case of bleeding events.
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biotest
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON plc, Phoenix Clinical Research, Accovion GmbH
- Responsible party
- Sponsor
- Investigators
- Claudia Djambas Khayat, MD, Principal investigator, Hôtel Dieu de France, Dept. of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02065882
- Sponsor's protocol ID
- Biotest 984
- Other IDs
- 2011-004154-25
- Status last verified
- Jun 2025
- First submitted
- 3 Feb 2014
- Last updated
- 3 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Khayat CD, El-Beshlawy A, Omar N, Belhadjali EG, Khelif A, Adolf S, Miesbach W, Aigner S, Abraha S, Schuettrumpf J, Boehm H. Efficacy and safety of prophylaxis and treatment of bleeding events with a novel fibrinogen concentrate from human plasma in patients with congenital fibrinogen deficiency. Thromb Res. 2026 Mar;259:109616. doi: 10.1016/j.thromres.2026.109616. Epub 2026 Feb 10.
PubMed 41702298
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02065882
- Acronym / sponsor ID
- Biotest 984
- Keywords
- fibrinogen, bleeding,
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- BiotestIndustry (pharma, biotech, devices)
- Collaborators
- ICON plc, Phoenix Clinical Research, Accovion GmbH
- Study start
- Mar 2013 (actual)
- Primary completion
- 18 May 2020 (actual)
- Study completion
- 18 Nov 2020 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Posted 3 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a prospective, open-label, multicenter, phase I/III study investigating the 14-day single-dose pharmacokinetic and pharmacodynamic 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.
Detailed description
The study was divided into two parts (Part I and Part II). Part I focused on the primary endpoint of the study, 14-day single-dose pharmacokinetics (PK) and 14-day single-dose pharmacodynamics (PD), as well as the assessment of maximum clot firmness (MCF) as a surrogate parameter for efficacy. Part I of the study was followed by Part II, which evaluated the efficacy and safety of single and repetitive administration of BT524 in patients undergoing on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) for various bleeding events [e.g., elective surgery, spontaneous or post-traumatic major bleeding]. All patients who participated in the PK assessment (Part I) without severe post-administration complications ideally continued treatment with BT524 for ODP and/or ODT in Part II.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study was divided into two parts: PK/PD Part I and Efficacy Part II. Patients eligible for PK/PD Part I received a fixed dose of 70 mg BT524 per kilogram body weight (BW) via a single intravenous infusion. Part I was followed by Part II. In Part II, patients received a variable, individually tailored dose of BT524 for on-demand prophylaxis (ODP) and/or on-demand treatment (ODT) in case of bleeding events.
| Arm | Type | Receives |
|---|---|---|
| BT524 | Experimental | Drug: BT524 (Part I), Drug: BT524 (Part II)Part I: A single intravenous infusion of BT524 for assessment of PK/PD of BT524. Part II: A single or repetitive intravenous infusion(s) of BT524 for on-demand prophylaxis/on-demand treatment of bleeding events. |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BT524 (Part I)Also: Human Fibrinogen ConcentrateSingle intravenous infusion of 70 mg BT524 per kg body weight. | Drug | BT524 |
| BT524 (Part II)Also: Human Fibrinogen ConcentrateSingle or repetitive intravenous infusion(s) of BT524, depending on the severity of the disorder, location and extent of the bleeding and patient's clinical condition. Dosage based on individual body weight and fibrinogen level. | Drug | BT524 |
Primary outcome
Single-dose Pharmacokinetics (PK) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
T1/2 of fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. T1/2 was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-dose Pharmacokinetics (PK) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Time of occurence of Cmax relative to dosing (Tmax) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Tmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/required).
Single-Dose Pharmacokinetics (PK) for BT524: Maximum Concentration (Cmax) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Maximum observed plasma concentration (Cmax) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Cmax was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
AUC0-tz: Area under the time course of the plasma concentrations calculated from time zero up to the last quantifiable plasma concentration for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUC0-tz was derived from time-concentration profiles using adapted methodology (noncompartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
AUCextr: extent of AUC extrapolation beyond last concentration for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUCextr was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
AUC0-∞: AUC from time 0 to infinity for fibrinogen antigen, was determined from samples taken at several time points during the 14 day sampling period. AUC0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
MRT0-∞: Mean Residence Time (MRT) extrapolated to infinity for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. MRT0-∞ was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Clearance (CL) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
CL: Total clearance (CL) for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. CL was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Vdss: Volume of distribution at presumed steady-state for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Vdss was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Antigen
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Vdss per kg BW: Volume of distribution at presumed steady-state per kg bodyweight for fibrinogen antigen was determined from samples taken at several time points during the 14 day sampling period. Vdss per kg BW was derived from time-concentration profiles using adapted methodology (non-compartmental analysis, compartment analysis, or population modeling, as appropriate/ required).
Single-Dose Pharmacokinetics (PK) for BT524: Incremental Recovery (IR) for Fibrinogen Antigen
Time frame: Between pre-dose and 4 hours post-dose
IR is the dose-adjusted maximum fibrinogen increase in plasma within 4 hours after the end of infusion.
Single-Dose Pharmacokinetics (PK) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Antigen
Time frame: Between pre-dose and 4 hours post-dose
CIR: maximum fibrinogen increase in plasma within 4 hours after the end of infusion divided by the maximum theoretical fibrinogen increase
16 secondary outcomes
Single-dose Pharmacodynamics (PD) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Maximum Concentration (Cmax) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-dose Pharmacodynamics (PD) of BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Clearance (CL) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Activity
Time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Incremental Recovery (IR) for Fibrinogen Activity
Time frame: Between pre-dose and 4 hours post-dose
Single-Dose Pharmacodynamics (PD) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Activity
Time frame: Between pre-dose and 4 hours post-dose
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion
Time frame: Part I: pre-dose and at 1 hour post-end of infusion. Part II: pre-dose and at 1 hour post-end of infusion of each bleeding event.
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II
Time frame: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II
Time frame: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Clinical Efficacy for BT524: Units of Other Fibrinogen-containing Products (FCP) Infused Besides BT524 in Study Part II
Time frame: Part II: Up to 24 hours after end of infusion, or on day of hospital discharge (if between 24 hours and 49 days post-infusion); at the latest on day 49 after the treated bleeding event.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41702298Khayat CD, El-Beshlawy A, Omar N, Belhadjali EG, Khelif A, Adolf S, Miesbach W, Aigner S, Abraha S, Schuettrumpf J, Boehm H. Efficacy and safety of prophylaxis and treatment of bleeding events with a novel fibrinogen concentrate from human plasma in patients with congenital fibrinogen deficiency. Thromb Res. 2026 Mar;259:109616. doi: 10.1016/j.thromres.2026.109616. Epub 2026 Feb 10.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Djambas Khayat, MD principal investigator
Hôtel Dieu de France, Dept. of Pediatrics
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BT524 (Part I) and BT524 (Part II) in people with Congenital Afibrinogenemia and Congenital Hypofibrinogenemia, run by Biotest at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Tunisia, Bulgaria, Egypt, Germany, Lebanon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Single-dose Pharmacokinetics (PK) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Antigen (time frame: Pre-dose on Dosing Day 0, at the end of the infusion and 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 240 and 336 hours post-dose). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02065882, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.