Trial Outcomes & Findings for Pharmacokinetic, Efficacy and Safety of BT524 in Patients With Congenital Fibrinogen Deficiency (NCT NCT02065882)

NCT ID: NCT02065882

Last Updated: 2025-07-03

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 67 participants
• Primary outcome timeframe: 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
• Results posted on: 2025-07-03

Participant Flow

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.

Participant milestones

Measure	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.
Part I: PK/PD STARTED	35
Part I: PK/PD Treated	27
Part I: PK/PD COMPLETED	27
Part I: PK/PD NOT COMPLETED	8
Part II: Clinical Efficacy STARTED	59
Part II: Clinical Efficacy Treated	36
Part II: Clinical Efficacy COMPLETED	28
Part II: Clinical Efficacy NOT COMPLETED	31

Reasons for withdrawal

Measure	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.
Part I: PK/PD Screening failure	5
Part I: PK/PD Withdrawal by Subject	2
Part I: PK/PD Adverse Event	1
Part II: Clinical Efficacy Screening failure	7
Part II: Clinical Efficacy Withdrawal by Subject	2
Part II: Clinical Efficacy Adverse Event	5
Part II: Clinical Efficacy Regulatory Authority Decision	3
Part II: Clinical Efficacy No Bleeding Event	11
Part II: Clinical Efficacy Protocol Violation	3

Baseline Characteristics

Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.

Baseline characteristics by cohort

Measure	BT524 (Human Fibrinogen Concentrate) n=67 Participants 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.
Age, Categorical Part I · <=18 years	12 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Categorical Part I · Between 18 and 65 years	15 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Categorical Part I · >=65 years	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Categorical Part II · <=18 years	16 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Categorical Part II · Between 18 and 65 years	20 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Categorical Part II · >=65 years	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Continuous Part I	17.6 years STANDARD_DEVIATION 11.82 • n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Age, Continuous Part II	19.6 years STANDARD_DEVIATION 11.76 • n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Sex: Female, Male Part I · Female	13 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Sex: Female, Male Part I · Male	14 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Sex: Female, Male Part II · Female	14 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Sex: Female, Male Part II · Male	22 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part I · Hispanic or Latino	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part I · Not Hispanic or Latino	27 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part I · Unknown or Not Reported	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part II · Hispanic or Latino	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part II · Not Hispanic or Latino	36 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Ethnicity (NIH/OMB) Part II · Unknown or Not Reported	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · American Indian or Alaska Native	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · Asian	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · Native Hawaiian or Other Pacific Islander	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · Black or African American	1 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · White	26 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · More than one race	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part I · Unknown or Not Reported	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · American Indian or Alaska Native	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · Asian	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · Native Hawaiian or Other Pacific Islander	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · Black or African American	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · White	36 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · More than one race	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Race (NIH/OMB) Part II · Unknown or Not Reported	0 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Region of Enrollment Lebanon	39 participants n=67 Participants
Region of Enrollment Egypt	12 participants n=67 Participants
Region of Enrollment Bulgaria	2 participants n=67 Participants
Region of Enrollment Tunisia	13 participants n=67 Participants
Region of Enrollment Germany	1 participants n=67 Participants
Maximum Clot Firmness Part I: Adults	1.2 mm STANDARD_DEVIATION 0.58 • n=12 Participants • 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.
Maximum Clot Firmness Part I: Adolescents, 12 to <18 years	1.0 mm STANDARD_DEVIATION 0 • n=2 Participants • 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.
Maximum Clot Firmness Part I: Children, 6 to <12 years	1.0 mm STANDARD_DEVIATION 0 • n=2 Participants • 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.
Maximum Clot Firmness Part I: Children, <6 years	1.0 mm STANDARD_DEVIATION 0 • n=6 Participants • 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.
Maximum Clot Firmness Part II: Adults	2.1 mm STANDARD_DEVIATION 4.03 • n=20 Participants • 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.
Maximum Clot Firmness Part II: Adolescents, 12 to <18 years	1.0 mm STANDARD_DEVIATION 0 • n=4 Participants • 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.
Maximum Clot Firmness Part II: Children, 6 to <12 years	1.0 mm STANDARD_DEVIATION 0 • n=9 Participants • 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.
Maximum Clot Firmness Part II: Children, <6 years	1.0 mm STANDARD_DEVIATION 0 • n=3 Participants • 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.
Fibrinogen Activity Part I: Adults	0.1750 g/L STANDARD_DEVIATION 0 • n=15 Participants • 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.
Fibrinogen Activity Part I: Adolescents, 12 to <18 years	0.1750 g/L STANDARD_DEVIATION 0 • n=3 Participants • 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.
Fibrinogen Activity Part I: Children, 6 to <12 years	0.1750 g/L STANDARD_DEVIATION 0 • n=3 Participants • 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.
Fibrinogen Activity Part I: Children, <6 years	0.1500 g/L STANDARD_DEVIATION 0 • n=6 Participants • 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.
Fibrinogen Activity Part II: Adults	0.1681 g/L STANDARD_DEVIATION 0.01856 • n=20 Participants • 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.
Fibrinogen Activity Part II: Adolescents, 12 to <18 years	0.1578 g/L STANDARD_DEVIATION 0.01611 • n=4 Participants • 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.
Fibrinogen Activity Part II: Children, 6 to <12 years	0.1553 g/L STANDARD_DEVIATION 0.02385 • n=9 Participants • 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.
Fibrinogen Activity Part II: Children, <6 years	0.1500 g/L STANDARD_DEVIATION 0 • n=3 Participants • 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.
Disease characteristics Part I · Afibrinogenemia	27 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Disease characteristics Part I · Severe Hypofibrinogenemia	0 Participants n=27 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Disease characteristics Part II · Afibrinogenemia	34 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.
Disease characteristics Part II · Severe Hypofibrinogenemia	2 Participants n=36 Participants • Part I: All participants treated with BT524, n=27. Part II: All participants treated with BT524, n=36.

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacokinetics (PK) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Antigen	67.9 hours Standard Deviation 15.3	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacokinetics (PK) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Antigen	0.843 hours Standard Deviation 0.361	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Maximum Concentration (Cmax) for Fibrinogen Antigen	1.81 g/L Standard Deviation 0.423	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Antigen	144 g*h/L Standard Deviation 38.9	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Antigen	17.1 percentage Standard Deviation 3.58	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Antigen	173 g*h/L Standard Deviation 45.4	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Antigen	133 hours Standard Deviation 17.4	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Clearance (CL) for Fibrinogen Antigen	0.0206 L/h Standard Deviation 0.00961	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Antigen	2.70 Liter Standard Deviation 1.34	—

PRIMARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Antigen	57.8 mL/kg Standard Deviation 19.1	—

PRIMARY outcome

Timeframe: Between pre-dose and 4 hours post-dose

Population: PK Set: consists of all patients of part I with PK data.

IR is the dose-adjusted maximum fibrinogen increase in plasma within 4 hours after the end of infusion.

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Incremental Recovery (IR) for Fibrinogen Antigen	2.63 (mg/dL)/(mg/kg dose) Standard Deviation 0.652	—

PRIMARY outcome

Timeframe: Between pre-dose and 4 hours post-dose

Population: PK Set: consists of all patients of part I with PK data.

CIR: maximum fibrinogen increase in plasma within 4 hours after the end of infusion divided by the maximum theoretical fibrinogen increase

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacokinetics (PK) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Antigen	118 % of expected increase in fibrinogen Standard Deviation 29.4	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Terminal Elimination Half-life (t1/2) for Fibrinogen Activity	60.3 hours Standard Deviation 13.3	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Time to Maximum Concentration (Tmax) for Fibrinogen Activity	0.843 hours Standard Deviation 0.361	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Maximum Concentration (Cmax) for Fibrinogen Activity	1.26 g/L Standard Deviation 0,396	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) Calculated to the Last Measured Concentration (AUC0-tz) for Fibrinogen Activity	88.2 g*h/L Standard Deviation 29.3	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Extent of Area Under the Curve (AUC) Extrapolation Beyond Last Concentration (AUCextr) for Fibrinogen Activity	15.4 percentage (extent of AUC extrapolation) Standard Deviation 3.41	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Area Under the Curve (AUC) From Time 0 to Infinity (AUC0-∞) for Fibrinogen Activity	104 g*h/L Standard Deviation 33.5	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-dose Pharmacodynamics (PD) of BT524: Mean Residence Time (MRT) Extrapolated to Infinity (MRT0-∞) for Fibrinogen Activity	124 hours Standard Deviation 16.2	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacodynamics (PD) for BT524: Clearance (CL) for Fibrinogen Activity	0.0351 L/h Standard Deviation 0.0179	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) for Fibrinogen Activity	4.31 Liter Standard Deviation 2.36	—

SECONDARY outcome

Timeframe: 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

Population: PK Set: consists of all patients of part I with PK data.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacodynamics (PD) for BT524: Volume of Distribution at Presumed Steady-state (Vdss) Per kg Body Weight (BW) for Fibrinogen Activity	92.4 mL/kg Standard Deviation 34.7	—

SECONDARY outcome

Timeframe: Between pre-dose and 4 hours post-dose

Population: PK Set: consists of all patients of part I with PK data.

IR is the dose-adjusted maximum fibrinogen increase in plasma within 4 hours after the end of infusion.

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacodynamics (PD) for BT524: Incremental Recovery (IR) for Fibrinogen Activity	1.88 (mg/dL)/(mg/kg dose) Standard Deviation 0.610	—

SECONDARY outcome

Timeframe: Between pre-dose and 4 hours post-dose

Population: PK Set: consists of all patients of part I with PK data.

CIR: maximum fibrinogen increase in plasma within 4 hours after the end of infusion divided by the maximum theoretical fibrinogen increase

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=27 Participants Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Single-Dose Pharmacodynamics (PD) for BT524: Classical in Vivo Recovery (CIR) for Fibrinogen Activity	84.8 % of expected increase in fibrinogen Standard Deviation 27.5	—

SECONDARY outcome

Timeframe: 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.

Population: 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

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.

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=19 BT524 infusion Part I: A single intravenous infusion of 70 mg BT524 per kg body weight for assessment of PK/PD of BT524.	Part II n=128 BT524 infusion A single or repetitive intravenous infusion(s) of BT524 for on-demand prophylaxis/on-demand treatment of bleeding events.
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion Adults	11.1 mm Standard Deviation 5.07	11.1 mm Standard Deviation 5.55
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion Adolescents, 12 to <18 years	11.0 mm Standard Deviation 2.83	9.8 mm Standard Deviation 5.28
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion Children, 6 to <12 years	16.5 mm Standard Deviation 3.54	11.1 mm Standard Deviation 4.57
Change in Maximum Clot Firmness at 1 Hour Post-end of Infusion Children, <6 years	9.3 mm Standard Deviation 1.53	8.7 mm Standard Deviation 5.51

SECONDARY outcome

Timeframe: 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.

Population: 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.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=175 Bleeding Events Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II Excellent	150 Bleeding Events	—
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II Good	23 Bleeding Events	—
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II Moderate	2 Bleeding Events	—
Clinical Efficacy for BT524: Overall Hemostatic Response to Treatment With BT524 in Study Part II None	0 Bleeding Events	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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).

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=54 Surgical bleeding events Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II Loss of blood is lower than expected for the procedure performed.	3 Surgical bleeding events	—
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II Loss of blood is within the expected range for the procedure performed.	45 Surgical bleeding events	—
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II Loss of blood is higher than expected for the procedure performed.	4 Surgical bleeding events	—
Clinical Efficacy for BT524: Total Loss of Blood for Surgical Bleeding Events in Study Part II Missing	2 Surgical bleeding events	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	BT524 (Human Fibrinogen Concentrate) n=175 Bleeding Events Part I: A single intravenous infusion of 70 mg BT524 per kg body weight 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.
Clinical Efficacy for BT524: Units of Other Fibrinogen-containing Products (FCP) Infused Besides BT524 in Study Part II	0 Number of FCP	—

Adverse Events

PK/PD Part I

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Part II

Serious events: 7 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Measure	PK/PD Part I n=27 participants at risk Part I: A single intravenous infusion of 70 mg BT524 per kg body weight for assessment of PK/PD of BT524.	Part II n=36 participants at risk Part II: A single or repetitive intravenous infusion(s) of BT524 as individually required, for on-demand prophylaxis/on-demand treatment of bleeding events.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Gastrointestinal disorders Pancreatitis	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Injury, poisoning and procedural complications Extradural heamatoma	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Haematoma muscle	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 1/27 • Number of events 1 • 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).	0.00% 0/36 • 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).
Nervous system disorders Epilepsy	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Nervous system disorders Hypertensive encephalopathy	3.7% 1/27 • Number of events 1 • 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).	0.00% 0/36 • 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).
Renal and urinary disorders Post streptococcal glomerulonephritis	3.7% 1/27 • Number of events 1 • 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).	0.00% 0/36 • 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).
Reproductive system and breast disorders Menorrhagia	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).
Vascular disorders Deep vein thrombosis	0.00% 0/27 • 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).	2.8% 1/36 • Number of events 1 • 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).

Other adverse events

Measure	PK/PD Part I n=27 participants at risk Part I: A single intravenous infusion of 70 mg BT524 per kg body weight for assessment of PK/PD of BT524.	Part II n=36 participants at risk Part II: A single or repetitive intravenous infusion(s) of BT524 as individually required, for on-demand prophylaxis/on-demand treatment of bleeding events.
Gastrointestinal disorders Gingival bleeding	3.7% 1/27 • Number of events 1 • 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).	5.6% 2/36 • Number of events 3 • 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).
Gastrointestinal disorders Toothache	7.4% 2/27 • Number of events 2 • 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).	8.3% 3/36 • Number of events 3 • 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).
General disorders Pyrexia	3.7% 1/27 • Number of events 1 • 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).	8.3% 3/36 • Number of events 3 • 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).
General disorders Swelling face	0.00% 0/27 • 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).	8.3% 3/36 • Number of events 3 • 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).
Infections and infestations Rhinitis	3.7% 1/27 • Number of events 1 • 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).	5.6% 2/36 • Number of events 2 • 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).
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/27 • 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).	5.6% 2/36 • Number of events 2 • 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).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/27 • 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).	25.0% 9/36 • Number of events 30 • 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).
Injury, poisoning and procedural complications Skin wound	0.00% 0/27 • 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).	5.6% 2/36 • Number of events 2 • 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).
Injury, poisoning and procedural complications Subcutaneous haematoma	3.7% 1/27 • Number of events 1 • 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).	16.7% 6/36 • Number of events 10 • 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).
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/27 • 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).	8.3% 3/36 • Number of events 3 • 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).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/27 • 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).	5.6% 2/36 • Number of events 2 • 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).
Musculoskeletal and connective tissue disorders Back pain	11.1% 3/27 • Number of events 4 • 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).	11.1% 4/36 • Number of events 5 • 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).
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/27 • 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).	5.6% 2/36 • Number of events 2 • 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).
Musculoskeletal and connective tissue disorders Osteorrhagia	0.00% 0/27 • 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).	8.3% 3/36 • Number of events 9 • 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).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/27 • 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).	11.1% 4/36 • Number of events 8 • 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).
Nervous system disorders Headache	3.7% 1/27 • Number of events 1 • 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).	5.6% 2/36 • Number of events 2 • 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).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/27 • 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).	11.1% 4/36 • Number of events 4 • 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).
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/27 • 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).	8.3% 3/36 • Number of events 3 • 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).
Vascular disorders Haematoma	0.00% 0/27 • 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).	5.6% 2/36 • Number of events 3 • 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).

Additional Information

Dr. Christina Erb

Biotest AG

Phone: 00496103801

Email: christina.erb@biotest.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER