Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2011-004154-25 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| ICON plc | INDUSTRY |
| Phoenix Clinical Research | OTHER |
| Accovion GmbH | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BT524 (Part I) | Drug | Single intravenous infusion of 70 mg BT524 per kg body weight. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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). | 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). | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Claudia Djambas Khayat, MD | Hôtel Dieu de France, Dept. of Pediatrics | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 15 | Sofia | Bulgaria | ||||
| Site 11 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41702298 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Part I and Part II of the study were conducted consecutively, enrolling a total of 67 participants. The total number of participants enrolled (N=67) is smaller than the sum of participants enrolled in Part I (N=35) and Part II (N=59), because 27 participants who successfully completed Part I were subsequently enrolled in Part II. Of the enrolled participants, N=27 in Part I and N=36 in Part II were treated with BT524, with 18 participants receiving BT524 in both parts of the study.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | BT542 (Human Fibrinogen Concentrate) | Part I: A single intravenous infusion of 70 mg BT524 per kg of body weight. Part II: Single or repetitive intravenous infusion(s) of BT524, as individually required. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part I: PK/PD |
|
| |||||||||||||||||||||||||||
| Part II: Clinical Efficacy |
|
Part I: Baseline characteristics were assessed in all participants who received any portion of BT524 (n=27).
Part II: Baseline characteristics were assessed in all participants who received any portion of BT524 (n=36).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BT524 (Human Fibrinogen Concentrate) | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
Day 0 to Day 49 (From the day of study drug administration until 49±4 days after the last administration of the study drug in Part I, up to 1 year in Part II.
Adverse Events (AEs) reported from the time of study drug administration to the safety visit on Day 49± 4 were recorded as treatment-emergent adverse events (TEAEs).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PK/PD Part I | Part I: A single intravenous infusion of 70 mg BT524 per kg body weight for assessment of PK/PD of BT524. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA version 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingival bleeding | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christina Erb | Biotest AG | 00496103801 | 0 | christina.erb@biotest.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 8, 2018 | Dec 11, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 2, 2020 | Dec 11, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 2, 2018 | Dec 12, 2024 | ICF_002.pdf |
| ID | Term |
|---|---|
| D000347 | Afibrinogenemia |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| BT524 (Part II) | Drug | 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. |
|
|
| 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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 | Between pre-dose and 4 hours post-dose |
| 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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 | 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. | 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). | 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). | 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. | 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. |
| Cairo |
| Egypt |
| Site 16 | Frankfurt | Germany |
| Site 01 | Beirut | Lebanon |
| Site 14 | Sousse | Tunisia |
| Site12 | Tunis | Tunisia |
| NOT COMPLETED |
|
|
| Count of Participants |
| Participants |
|
| Age, Continuous | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Maximum Clot Firmness | Part I: All particpiants treated with BT524, n=27; MCF values were available for 22 participants. Data were missing for 5 participants: 3 adults, 1 adolescent, 1 child (aged 6 to <12 y). Part II: All participants treated with BT524, n=36. | Mean | Standard Deviation | mm |
|
| Fibrinogen Activity | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. Fibrinogen Activity was measured in all participants prior to BT524 treatment. | Mean | Standard Deviation | g/L |
|
| Disease characteristics | Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36. | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g/L | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g*h/L | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | percentage | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g*h/L | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | L/h | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | Liter | 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 |
|
|
|
| Primary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | mL/kg | 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 |
|
|
|
| Primary | 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. | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | (mg/dL)/(mg/kg dose) | Between pre-dose and 4 hours post-dose |
|
|
|
| Primary | 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 | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | % of expected increase in fibrinogen | Between pre-dose and 4 hours post-dose |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g/L | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g*h/L | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | percentage (extent of AUC extrapolation) | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | g*h/L | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | L/h | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | Liter | 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 |
|
|
|
| Secondary | 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). | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | mL/kg | 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 |
|
|
|
| Secondary | 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. | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | (mg/dL)/(mg/kg dose) | Between pre-dose and 4 hours post-dose |
|
|
|
| Secondary | 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 | PK Set: consists of all patients of part I with PK data. | Posted | Mean | Standard Deviation | % of expected increase in fibrinogen | Between pre-dose and 4 hours post-dose |
|
|
|
| Secondary | 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. | Full analysis set (FAS I/II): all patients who received any portion of BT524 and had at least one efficacy assessment in part I/part II | Posted | Mean | Standard Deviation | mm | 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. | BT524 infusion | BT524 infusion |
|
|
|
|
| Secondary | 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). | Full bleeding event set (FBE): All bleeding events treated with any portion of BT524 and with at least one efficacy assessment during part II of the study. | Posted | Count of Units | Bleeding Events | 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. | Bleeding Events | Bleeding Events |
|
|
|
| Secondary | 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). | Full bleeding event set (FBE): All bleeding events treated with any portion of BT524 and with at least one efficacy assessment during part II of the study. | Posted | Count of Units | Surgical bleeding events | 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. | Surgical bleeding events | Surgical bleeding events |
|
|
|
| Secondary | 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. | Full bleeding event set (FBE): All bleeding events treated with any portion of BT524 and with at least one efficacy assessment during part II of the study. | Posted | Number | Number of FCP | 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. | Bleeding Events | Bleeding Events |
|
|
|
| 0 |
| 27 |
| 2 |
| 27 |
| 10 |
| 27 |
| EG001 | Part II | Part II: A single or repetitive intravenous infusion(s) of BT524 as individually required, for on-demand prophylaxis/on-demand treatment of bleeding events. | 1 | 36 | 7 | 36 | 25 | 36 |
| Pancreatitis | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Extradural heamatoma | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Traumatic haemorrhage | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Haematoma muscle | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Hypertensive encephalopathy | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Post streptococcal glomerulonephritis | Renal and urinary disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Swelling face | General disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
|
| Procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Skin wound | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Osteorrhagia | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA version 23.0 | Systematic Assessment |
|
Not provided
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Adolescents, 12 to <18 years |
|
|
| Children, 6 to <12 years |
|
|
| Children, <6 years |
|
|
| None |
|
| Missing |
|