Trial Outcomes & Findings for Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency (NCT NCT02408484)

NCT ID: NCT02408484

Last Updated: 2021-01-15

Results Overview

The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4-point haemostatic efficacy scale (excellent, good, moderate or none). Excellent result was defined as immediate cessation of bleeding; 'Good' was eventual complete cessation of bleeding; 'Moderate' was incomplete cessation of bleeding and 'None' was no cessation of bleeding with alternative haemostatic intervention required. The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 15 participants
• Primary outcome timeframe: First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last
• Results posted on: 2021-01-15

Participant Flow

Participant milestones

Measure	Octafibrin Of the 15 patients screened,14 patients received at least one infusion of Octafibrin and were included in the study safety (SAF) and full-analysis set (FAS) populations. For the pharmacokinetic (PK) assessment, 13 patients received a single intravenous infusion of 70mg/kg body weight (BW) of Octafibrin. Dosage of Octafibrin when treating bleeding \& surgeries was individually dosed to achieve recommended target fibrinogen plasma levels.8 patients had at least 1 bleeding episode (BE) treated with Octafibrin and constitute the first bleeding (firstBLEED) population, and 8 patients had all documented BEs treated with Octafibrin and therefore constitute the all bleeding (BLEED) population. Target fibrinogen plasma level for minor bleeding were 80-100 mg/dL; major bleeding:130-150mg/dL. 3 patients underwent surgical interventions with at least 1 infusion of Octafibrin (SURG population). Target fibrinogen plasma level for minor surgeries: 80-100 mg/dL; major surgeries: 130-150 mg/dL.
Overall Study STARTED	15
Overall Study SAF Population	14
Overall Study FAS Population	14
Overall Study PK Population	13
Overall Study firstBLEED Population	8
Overall Study BLEED Population	8
Overall Study SURG Population	3
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Octafibrin Of the 15 patients screened,14 patients received at least one infusion of Octafibrin and were included in the study safety (SAF) and full-analysis set (FAS) populations. For the pharmacokinetic (PK) assessment, 13 patients received a single intravenous infusion of 70mg/kg body weight (BW) of Octafibrin. Dosage of Octafibrin when treating bleeding \& surgeries was individually dosed to achieve recommended target fibrinogen plasma levels.8 patients had at least 1 bleeding episode (BE) treated with Octafibrin and constitute the first bleeding (firstBLEED) population, and 8 patients had all documented BEs treated with Octafibrin and therefore constitute the all bleeding (BLEED) population. Target fibrinogen plasma level for minor bleeding were 80-100 mg/dL; major bleeding:130-150mg/dL. 3 patients underwent surgical interventions with at least 1 infusion of Octafibrin (SURG population). Target fibrinogen plasma level for minor surgeries: 80-100 mg/dL; major surgeries: 130-150 mg/dL.
Overall Study Withdrawal by Subject	3
Overall Study Not treated during study period	1

Baseline Characteristics

Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency

Baseline characteristics by cohort

Measure	Octafibrin n=14 Participants The full analysis set (FAS) population defined according to the intention-to-treat principle, included the 14 patients who received at least one infusion of Octafibrin, and entered the study with a confirmed congenital fibrinogen deficiency.
Age, Continuous	6 years STANDARD_DEVIATION 2.57 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	10 Participants n=5 Participants
Body Mass Index (BMI)	15.7 kg/m^2 STANDARD_DEVIATION 2.82 • n=5 Participants
Weight	19.8 kilograms (kg) STANDARD_DEVIATION 6.93 • n=5 Participants
Height	111.3 centimetres (cm) STANDARD_DEVIATION 15.37 • n=5 Participants

PRIMARY outcome

Timeframe: First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last

Population: The analysis was performed in the firstBLEED population which included patients in the full-analysis (FAS) population who had at least one bleeding episode treated with Octafibrin (n=8).

The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last.

The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4-point haemostatic efficacy scale (excellent, good, moderate or none). Excellent result was defined as immediate cessation of bleeding; 'Good' was eventual complete cessation of bleeding; 'Moderate' was incomplete cessation of bleeding and 'None' was no cessation of bleeding with alternative haemostatic intervention required.

The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.

Outcome measures

Measure	Investigator Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale Excellent	5 Participants	6 Participants
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale Good	1 Participants	2 Participants
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale Moderate	1 Participants	0 Participants
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale None	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last.

Population: The analysis was performed in the firstBLEED population which included patients in the full-analysis (FAS) population who had at least one bleeding episode treated with Octafibrin (n=8).

The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last.

The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 2-point haemostatic efficacy scale (success and failure). Efficacy rating of excellent or good on the four-point scale (above) indicated success and efficacy rating of moderate or none indicated failure.

The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.

Outcome measures

Measure	Investigator Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 2-point Haemostatic Efficacy Scale Success	6 Participants	8 Participants
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 2-point Haemostatic Efficacy Scale Failure	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level (n=13).

AUCnorm (Area under the concentration-time curve normalized to the dose administered) was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Area Under the Concentration-time Curve Normalised (AUCnorm)	1.419 h*kg*g/L/mg Standard Deviation 0.4385	—

SECONDARY outcome

Timeframe: Between the pre-infusion and the 3-hour post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level (n=13)

IVR was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Response - Incremental in Vivo Recovery (IVR)	1.592 mg/dL/(mg/kg) Standard Deviation 0.3224	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level (n=13).

t1/2 was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Terminal Elimination Half-life (t1/2)	84.356 hours Standard Deviation 34.2658	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level.

Cmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Maximum Plasma Concentration (Cmax)	1.559 g/L Standard Deviation 0.3183	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level (n=13).

Tmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Time to Reach Maximum Plasma Concentration (Tmax)	1.154 hours Standard Deviation 0.5547	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level (n=13).

MRT was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Mean Residence Time (MRT)	114.332 hours Standard Deviation 37.9732	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level.

Vss was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Volume of Distribution (Vss)	81.651 mL/kg Standard Deviation 15.2735	—

SECONDARY outcome

Timeframe: Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Population: The analysis was performed in the pharmacokinetic (PK) population, which included all patients in the full-analysis (FAS) population who underwent PK assessment and had at least one valid post-baseline fibrinogen activity level.

Cl was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=13 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Single-dose Pharmacokinetics of Octafibrin: Clearance (Cl)	0.756 mL/h/kg Standard Deviation 0.1872	—

SECONDARY outcome

Timeframe: Before first infusion and 1 hour post-infusion of Octafibrin

Population: The analysis was performed in patients in the full-analysis set population that had at least one bleeding episode (BE) treated with Octafibrin (firstBLEED population: n=8), and all patients that had all documented BEs treated with Octafibrin (BLEED population: n=8)

MCF was measured using thromboelastometry (ROTEM). ROTEM is a method for the continuous measurement of clot formation and clot firmness. It utilises a mechanical detection system which is based on the ability of the blood or plasma clot to form a mechanical coupling over a distance of 1 mm.

ROTEM was used to measure MCF as a surrogate efficacy marker for haemostatic efficacy before and after the first infusion of Octafibrin for treatment of the first bleeding episode and all bleeding episodes. The change in MCF was measured from baseline to 1 hour post-infusion of Octafibrin administration.

Outcome measures

Measure	Investigator Assessment n=8 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=10 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Change in Maximum Clot Firmness (MCF) for the First Bleeding Episode for Each Patients and for All Bleeding Episodes	3.1 millimeter (mm) Standard Deviation 1.96	3.3 millimeter (mm) Standard Deviation 1.77

SECONDARY outcome

Timeframe: Pre-infusion and 1 hour post-infusion of Octafibrin

Population: The analysis was performed in patients in the full-analysis set population that had at least one bleeding episode (BE) treated with Octafibrin (firstBLEED population: n=8), and all patients that had all documented BEs treated with Octafibrin (BLEED population: n=8)

Change in fibrinogen level was assessed using the Clauss fibrinogen assay for the first bleeding episode and all bleeding episodes. The change in fibrinogen level was assessed from Day 1 pre-infusion to 1 hour post-infusion of Octafibrin.

Outcome measures

Measure	Investigator Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Change in the Fibrinogen Level for All Bleeding Episodes up to 1 Hour-post Infusion for the First Bleeding Episode and All Bleeding Episodes	98.9 fibrinogen level (mg/dL) Standard Deviation 13.56	98.1 fibrinogen level (mg/dL) Standard Deviation 13.33

SECONDARY outcome

Timeframe: Pre-infusion and 3 hours post-infusion

Population: The analysis was performed in patients in the full-analysis set population that had at least one bleeding episode (BE) treated with Octafibrin (firstBLEED population: n=8), and all patients that had all documented BEs treated with Octafibrin (BLEED population: n=8)

Incremental IVR calculated as the maximum increase in plasma fibrinogen (i.e. Clauss data) between the pre-infusion and the 3-hour post-infusion measurement, (expressed as absolute concentration in plasma [mg/dL]), divided by the exact dose of Octafibrin per body weight (expressed as mg/kg dosed).

Incremental (response) IVR data for the firstBLEED and BLEED populations were calculated.

Outcome measures

Measure	Investigator Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=8 Participants Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Incremental in Vivo Recovery Following the First Infusion of Octafibrin Administration for the Treatment of the First Bleeding Episode and of All Bleeding Episodes	1.5 (mg/dL)/(mg/kg) Standard Deviation 0.29	1.5 (mg/dL)/(mg/kg) Standard Deviation 0.34

SECONDARY outcome

Timeframe: First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last

Population: The analysis was performed in patients in the full-analysis set population that had all documented bleeding episodes treated with Octafibrin (BLEED population: n=8)

The haemostatic efficacy of Octafibrin in the on-demand treatment of all bleeding episodes was based on a 4-point haemostatic efficacy scale ranging from excellent, good moderate and none. The efficacy assessment of each patients was assessed by the Investigator and the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC).

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Outcome measures

Measure	Investigator Assessment n=10 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=10 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale Excellent	7 Number of bleeding episodes	8 Number of bleeding episodes
Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale Good	1 Number of bleeding episodes	2 Number of bleeding episodes
Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale Moderate	1 Number of bleeding episodes	0 Number of bleeding episodes
Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale None	1 Number of bleeding episodes	0 Number of bleeding episodes

SECONDARY outcome

Timeframe: First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last

Population: The analysis was performed in patients in the full-analysis set population that had all documented bleeding episodes treated with Octafibrin (BLEED population: n=8)

The haemostatic efficacy of Octafibrin in the on-demand treatment of all bleeding episodes was based on a 2-point haemostatic efficacy scale ranging from success to failure. The efficacy assessment of each patients was assessed by the Investigator and the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC).

Outcome measures

Measure	Investigator Assessment n=10 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=10 Number of bleeding episodes Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Efficacy of Octafibrin in All Bleeding Episodes Based on a Two-point Haemostatic Efficacy Scale Success	8 Number of bleeding episodes	10 Number of bleeding episodes
Efficacy of Octafibrin in All Bleeding Episodes Based on a Two-point Haemostatic Efficacy Scale Failure	2 Number of bleeding episodes	0 Number of bleeding episodes

SECONDARY outcome

Timeframe: First dose of Octafibrin prior to surgery until last day of post-operative infusion

Population: The analysis was performed in patients in the full-analysis set population with documented surgical interventions treated with at least one infusion of Octafibrin (n=3).

The haemostatic efficacy of Octafibrin was assessed during surgery prophylaxis by the surgeon and the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC), on a 4-point scale ranging from excellent, good, moderate and none. Intra-operative blood loss lower or equal to the average expected blood loss was rates as 'Excellent'; intra-operative blood loss higher than average expected blood loss but lower or equal to maximal expected blood loss was rated as 'Good'; intra-operative blood loss was higher than expected blood loss was rated as 'Moderate' and haemostasis that was uncontrolled and necessitated a change in clotting factor replacement regimen was rated as 'None'.

The surgical observation period started lasted from the first dose of Octafibrin to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or until the day of the last post-operative infusion, whichever comes last.

Outcome measures

Measure	Investigator Assessment n=3 Number of surgeries Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=3 Number of surgeries Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale Excellent	3 Number of surgeries	3 Number of surgeries
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale Good	0 Number of surgeries	0 Number of surgeries
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale Moderate	0 Number of surgeries	0 Number of surgeries
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale None	0 Number of surgeries	0 Number of surgeries

SECONDARY outcome

Timeframe: First dose of Octafibrin prior to surgery until last day of post-operative infusion

Population: The analysis was performed in patients in the full-analysis set population with documented surgical interventions treated with at least one infusion of Octafibrin (n=3).

The haemostatic efficacy of Octafibrin was assessed during surgery prophylaxis by the surgeon and the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC), on a 2-point scale ranging from success to failure.

Efficacy rating of excellent or good from the 2-point efficacy scale indicated 'Success', and efficacy rating of moderate or none indicated 'Failure'.

The surgical observation period started lasted from the first dose of Octafibrin to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or until the day of the last post-operative infusion, whichever comes last.

Outcome measures

Measure	Investigator Assessment n=3 Number of surgeries Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment n=3 Number of surgeries Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Two-point Haemostatic Efficacy Scale Success	3 Number of surgeries	3 Number of surgeries
Efficacy of Octafibrin in Surgical Prophylaxis Based on a Two-point Haemostatic Efficacy Scale Failure	0 Number of surgeries	0 Number of surgeries

SECONDARY outcome

Timeframe: 3 hours post-infusion of Octafibrin

Population: The analysis was performed in all patients in the safety population that met the study inclusion criteria and received at least one infusion of Octafibrin (n=14).

Thrombogenicity was assessed by measuring the plasma levels of prothrombin fragment 1 (F1) and prothrombin fragment 2 (F2), before and after each Octafibrin infusion for the treatment of bleeding episodes during the study. This outcome measure examined the number of patients with elevated values of prothrombin fragments F1 + F2 that were outside of the reference range of 69 to 229 pmol/L, three hours post-infusion with Octafibrin.

Outcome measures

Measure	Investigator Assessment n=14 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Patients With Elevated Values of Prothrombin Fragments 1+2	3 Participants	—

SECONDARY outcome

Timeframe: Start of the first Octafibrin infusion to the end of each 30-day observation and follow-up period for on-demand treatment

Population: The analysis was performed in all patients in the safety population that met the inclusion criteria and received at least one infusion of Octafibrin during the study (n=14)

The number of patients developing anti-fibrinogen antibodies were observed during the observation period using an experimental non-standard ELISA quantitative laboratory test.

Immunogenicity testing for the presence of anti-fibrinogen antibodies before the first infusion of Octafibrin and on Day 30 after the treatment of each bleeding episode.

Outcome measures

Measure	Investigator Assessment n=14 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Safety Assessment: Immunogenicity Testing for Anti-fibrinogen Antibodies	2 Participants	—

SECONDARY outcome

Timeframe: Start of the first Octafibrin infusion to the end of PK, end of 30-day observation and follow-up period for on-demand treatment, or the end of the surgical observation period

Population: The analysis was performed in all patients in the safety population that met the inclusion criteria and received at least one infusion of Octafibrin during the study (n=14)

Adverse events, including thromboembolic complications and early signs of allergic or hypersensitivity reactions.

Outcome measures

Measure	Investigator Assessment n=14 Participants Efficacy rating on a 4-point efficacy scale as assessed by the Investigator	IDMEAC Assessment Efficacy rating on a 4-point efficacy scale as assessed by the IDMEAC
Safety Assessment: Adverse Events	10 Number of adverse events	—

Adverse Events

Octafibrin

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Octafibrin n=14 participants at risk The safety population consists of all patients that met the inclusion criteria and received at least one infusion of Octafibrin (n=14)
Hepatobiliary disorders Portal Vein Thrombosis	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.

Other adverse events

Measure	Octafibrin n=14 participants at risk The safety population consists of all patients that met the inclusion criteria and received at least one infusion of Octafibrin (n=14)
Skin and subcutaneous tissue disorders Ecchymosis	14.3% 2/14 • Number of events 3 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
General disorders Influenza-like illness	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
General disorders Pyrexia	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
Gastrointestinal disorders Abdominal pain	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
Infections and infestations Tonsillitis	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
Injury, poisoning and procedural complications Procedural pain	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.
Musculoskeletal and connective tissue disorders Haemarthrosis	7.1% 1/14 • Number of events 1 • Between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period or during the surgical observation period, and were absent prior to treatment or worsened relative to the pre-treatment state.

Additional Information

Sigurd Knaub

Octapharma

Phone: 55 451 21 41

Email: sigurd.knaub@octapharma.com

Results disclosure agreements

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