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This study will assess the efficacy of Octafibrin, a fibrinogen concentrate in in the on-demand treatment of spontaneous or traumatic bleeding episodes in paediatric patients less than 12 years of age.The planned study duration is up to 5 years. The study will be considered completed when a minimum of 6 subjects (i.e., at least 3 subjects aged between 0 and <6 years and 3 subjects aged between 6 and <12 years) have at least one documented bleeding episode and when in total a minimum of 2 surgical procedures have been performed.
All patients will undergo a pharmacokinetic (PK) study after screening. This will have a duration of 14 days, after which a patient can be treated for a bleeding episode or planned surgical procedure when they occur.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Octafibrin | Experimental | Plasma-derived fibrinogen concentrate |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octafibrin | Biological | Plasma-derived Fibrinogen concentrate |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 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 |
| 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 | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Single-dose Pharmacokinetics of Octafibrin: Area Under the Concentration-time Curve Normalised (AUCnorm) | 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. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
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Inclusion Criteria:
Exclusion Criteria:
Life expectancy <6 months.
Bleeding disorder other than congenital fibrinogen deficiency, including dysfi-brinogenaemia.
Prophylactic treatment with a fibrinogen concentrate.
Treatment with:
Presence or history of:
Known positive HIV infection with a viral load >200 particles/μL or >400,000 copies/mL.
Polytrauma 1 year prior to start of treatment for the bleeding episode or surgery.
Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or any time in the past.
Acute or chronic medical condition which may, in the opinion of investigator, affect the conduct of the study, including subjects receiving immune-modulating drugs (other than anti-retroviral chemotherapy), such as alpha-interferon, predni-sone (equivalent to >10 mg/day), or similar drugs, at study start.
Treatment with IMP in another interventional clinical study currently or during the past 4 weeks.
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| Name | Affiliation | Role |
|---|---|---|
| Cristina Solomon, MD | Octapharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. John's Medical College Hospital | Bangalore | 560034 | India | |||
| S.S Institute of Medical Science and Research Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Octafibrin | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at informed consent |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | 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). | Posted | Count of Participants | Participants | 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 |
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Octafibrin | The safety population consists of all patients that met the inclusion criteria and received at least one infusion of Octafibrin (n=14) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Portal Vein Thrombosis | Hepatobiliary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ecchymosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sigurd Knaub | Octapharma | 55 451 21 41 | +41 (0) | sigurd.knaub@octapharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 30, 2017 | Dec 21, 2020 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 2, 2017 | Dec 21, 2020 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D005340 | Fibrinogen |
| ID | Term |
|---|---|
| D000209 | Acute-Phase Proteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Single-dose Pharmacokinetics of Octafibrin: Response - Incremental in Vivo Recovery (IVR) | IVR was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Between the pre-infusion and the 3-hour post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Terminal Elimination Half-life (t1/2) | t1/2 was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Maximum Plasma Concentration (Cmax) | Cmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Time to Reach Maximum Plasma Concentration (Tmax) | Tmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Mean Residence Time (MRT) | MRT was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Volume of Distribution (Vss) | Vss was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Single-dose Pharmacokinetics of Octafibrin: Clearance (Cl) | Cl was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
| Change in Maximum Clot Firmness (MCF) for the First Bleeding Episode for Each Patients and for All Bleeding Episodes | 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. | Before first infusion and 1 hour post-infusion of Octafibrin |
| Change in the Fibrinogen Level for All Bleeding Episodes up to 1 Hour-post Infusion for the First Bleeding Episode and All Bleeding Episodes | 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. | Pre-infusion and 1 hour post-infusion of Octafibrin |
| Incremental in Vivo Recovery Following the First Infusion of Octafibrin Administration for the Treatment of the First Bleeding Episode and of All Bleeding Episodes | 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. | Pre-infusion and 3 hours post-infusion |
| Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale | 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). . | 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 |
| Efficacy of Octafibrin in All Bleeding Episodes Based on a Two-point Haemostatic Efficacy Scale | 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). | 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 |
| Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale | 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. | First dose of Octafibrin prior to surgery until last day of post-operative infusion |
| Efficacy of Octafibrin in Surgical Prophylaxis Based on a Two-point Haemostatic Efficacy Scale | 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. | First dose of Octafibrin prior to surgery until last day of post-operative infusion |
| Patients With Elevated Values of Prothrombin Fragments 1+2 | 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. | 3 hours post-infusion of Octafibrin |
| Safety Assessment: Immunogenicity Testing for Anti-fibrinogen Antibodies | 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. | Start of the first Octafibrin infusion to the end of each 30-day observation and follow-up period for on-demand treatment |
| Safety Assessment: Adverse Events | Adverse events, including thromboembolic complications and early signs of allergic or hypersensitivity reactions. | 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 |
| Davangere |
| 577005 |
| India |
| Nemazee Hospital Shiraz University of Medical Sciences | Shiraz | Iran |
| Hotel De Dieu de France | Beirut | Lebanon |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Weight | Mean | Standard Deviation | kilograms (kg) |
|
| Height | Mean | Standard Deviation | centimetres (cm) |
|
|
|
|
| Primary | 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 | 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. | 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). | Posted | Count of Participants | Participants | 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. |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Area Under the Concentration-time Curve Normalised (AUCnorm) | 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. | 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). | Posted | Mean | Standard Deviation | h*kg*g/L/mg | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Response - Incremental in Vivo Recovery (IVR) | IVR was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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) | Posted | Mean | Standard Deviation | mg/dL/(mg/kg) | Between the pre-infusion and the 3-hour post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Terminal Elimination Half-life (t1/2) | t1/2 was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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). | Posted | Mean | Standard Deviation | hours | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Maximum Plasma Concentration (Cmax) | Cmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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. | Posted | Mean | Standard Deviation | g/L | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Time to Reach Maximum Plasma Concentration (Tmax) | Tmax was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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). | Posted | Mean | Standard Deviation | hours | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Mean Residence Time (MRT) | MRT was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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). | Posted | Mean | Standard Deviation | hours | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Single-dose Pharmacokinetics of Octafibrin: Volume of Distribution (Vss) | Vss was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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. | Posted | Mean | Standard Deviation | mL/kg | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
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| Secondary | Single-dose Pharmacokinetics of Octafibrin: Clearance (Cl) | Cl was assessed after a single intravenous infusion of 70 mg/kg body weight of Octafibrin. | 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. | Posted | Mean | Standard Deviation | mL/h/kg | Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion |
|
|
|
| Secondary | Change in Maximum Clot Firmness (MCF) for the First Bleeding Episode for Each Patients and for All Bleeding Episodes | 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. | 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) | Posted | Mean | Standard Deviation | millimeter (mm) | Before first infusion and 1 hour post-infusion of Octafibrin | Number of bleeding episodes | Number of bleeding episodes |
|
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|
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| Secondary | Change in the Fibrinogen Level for All Bleeding Episodes up to 1 Hour-post Infusion for the First Bleeding Episode and All Bleeding Episodes | 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. | 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) | Posted | Mean | Standard Deviation | fibrinogen level (mg/dL) | Pre-infusion and 1 hour post-infusion of Octafibrin |
|
|
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| Secondary | Incremental in Vivo Recovery Following the First Infusion of Octafibrin Administration for the Treatment of the First Bleeding Episode and of All Bleeding Episodes | 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. | 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) | Posted | Mean | Standard Deviation | (mg/dL)/(mg/kg) | Pre-infusion and 3 hours post-infusion |
|
|
|
| Secondary | Efficacy of Octafibrin in All Bleeding Episodes Based on a Four-point Haemostatic Efficacy Scale | 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). . | 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) | Posted | Count of Units | Number of bleeding episodes | 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 | Number of bleeding episodes | Number of bleeding episodes |
|
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| Secondary | Efficacy of Octafibrin in All Bleeding Episodes Based on a Two-point Haemostatic Efficacy Scale | 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). | 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) | Posted | Count of Units | Number of bleeding episodes | 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 | Number of bleeding episodes | Number of bleeding episodes |
|
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| Secondary | Efficacy of Octafibrin in Surgical Prophylaxis Based on a Four-point Haemostatic Efficacy Scale | 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. | 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). | Posted | Count of Units | Number of surgeries | First dose of Octafibrin prior to surgery until last day of post-operative infusion | Number of surgeries | Number of surgeries |
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| Secondary | Efficacy of Octafibrin in Surgical Prophylaxis Based on a Two-point Haemostatic Efficacy Scale | 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. | 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). | Posted | Count of Units | Number of surgeries | First dose of Octafibrin prior to surgery until last day of post-operative infusion | Number of surgeries | Number of surgeries |
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| Secondary | Patients With Elevated Values of Prothrombin Fragments 1+2 | 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. | 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). | Posted | Count of Participants | Participants | 3 hours post-infusion of Octafibrin |
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| Secondary | Safety Assessment: Immunogenicity Testing for Anti-fibrinogen Antibodies | 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. | 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) | Posted | Count of Participants | Participants | Start of the first Octafibrin infusion to the end of each 30-day observation and follow-up period for on-demand treatment |
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| Secondary | Safety Assessment: Adverse Events | Adverse events, including thromboembolic complications and early signs of allergic or hypersensitivity reactions. | 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) | Posted | Number | Number of adverse events | 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 |
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| 0 |
| 14 |
| 1 |
| 14 |
| 4 |
| 14 |
| Influenza-like illness | General disorders | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Tonsillitis | Infections and infestations | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | Systematic Assessment |
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| Haemarthrosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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Not provided
Not provided
| D001779 |
| Blood Coagulation Factors |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
p-value for the change in MCF from baseline to 1 hour post infusion for the BLEED population |
| Other |
| Moderate |
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| None |
|
| Moderate |
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| None |
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