Factor X Deficiency
Conditions
Keywords
Factor X deficiency, surgery, Factor X deficiency subjects requiring surgery
Brief summary
To primary efficacy variable is to assess the presence or absence of excessive blood loss during and after surgery. The secondary efficacy endpoints are as follows: 1. A subjective overall assessment by the investigator of FACTOR X in the control of bleeding during surgery. 2. The incidence of bleeding episodes during treatment with FACTOR X while the subject is at risk of post-operative bleeding, including location and duration. 3. Incremental recovery of FX:C and FX:Ag after the pre-surgery bolus infusion. 4. Assessment of FX:C and FX:Ag levels on each day post-surgery. 5. Assessment of the cumulative weight-adjusted doses of FACTOR X as measured by FX:C (IU/kg body weight) administered to each subject to maintain haemostasis. 6. Assessment of the cumulative doses of FACTOR X as measured by FX:C (IU) administered to each subject to maintain haemostasis. 7. Amount of weight-adjusted FACTOR X as measured by FX:C (IU/kg body weight) administered daily (day of surgery and each post-operative day) to maintain haemostasis.
Detailed description
To investigate the safety and efficacy of FACTOR X administered by bolus infusion to prevent bleeding and achieve haemostasis in factor X deficient subjects undergoing surgery.
Interventions
BIOLOGICALFACTOR X
Presurgery loading dose- The FX level of 70%-90% should be achieved.This will be calculated based on the patients weight on day of surgery and the required rise. Initial dose should not exceed 60IU/kg. Post surgery- FX trough levels of 50% should be achieved. Intravenous infusion of factor X is given at a suggested rate of 10mL/min but not exceeding more than 20mL/min.
Sponsors
Bio Products Laboratory
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects who are at least 12 years of age at date of written informed consent/assent. * Subjects who have given written informed consent or, for subjects aged 12-17 years (inclusive), have given written assent and whose parent/guardian has given written informed consent. * Subjects with hereditary mild to severe Factor X deficiency (\<20% basal FX activity), including previously untreated subjects OR those currently treated with Fresh Frozen Plasma (FFP), Prothrombin Complex Concentrate (PCC) or factor IX/X concentrate by prophylaxis or on demand. * Subjects who are to undergo surgery in which the investigator believes a factor X concentrate will be required due to a prior history of unusual bleeding either spontaneously or after surgery or trauma in the absence of treatment with a factor X containing product. * Pregnant subjects undergoing obstetric delivery (including Caesarean surgery and vaginal delivery) may enter the study. Female subjects of child-bearing potential must have a negative result on a human chorionic gonadotropin-based pregnancy test. If a female subject is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.
Exclusion criteria
* Subjects who are required or expected to take other factor X containing medications during or after surgery. * Subjects with a history of inhibitor development to FX or a detectable inhibitor to FX (≥0.6 BU) on the Nijmegen-Bethesda assay at screening. Obtaining a FX inhibitor result at screening is not mandatory if the subject is to undergo emergency surgery and the local laboratory is unable to perform the analyses prior to the surgical procedure. * Subjects with thrombocytopenia (platelets \< 50 x 109/L). * Subjects who have clinically significant renal disease (creatinine \>200µmol/L). * Subjects who have clinically significant liver disease (ALT levels greater than three times the upper limit of normal). * Subjects known to have other coagulopathy or thrombophilia. * Subjects who are currently participating or have participated in another trial within the last 30 days, with the exception of the BPL Factor X PK study (protocol number Ten01). * Female subjects who are lactating. * Subjects who have known or suspected hypersensitivity to the investigational medicinal product or its excipients. * Subjects known to have abused chemicals or drugs within the past 12 months. * Subjects with a history of unreliability or non-cooperation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Degree of Bleeding Control Rated as Excellent. | During and till end of treatment | Investigators made an overall assessment of FACTOR X in controlling bleeding at the End of Treatment Assessment. The degree of bleeding control was rated as excellent, good, poor or unassessable, in accordance with the following criteria listed below: * Excellent -Parameters were similar to those in subjects without a bleeding disorder. * Good -Parameters were inferior to those in subjects without a bleeding disorder, but no other factor X containing agents were required to restore haemostasis. * Poor - Blood loss was excessive (defined as more than twice the pre defined amount that would be expected in a subject without a bleeding disorder for this type of surgery) and/or Haemostasis was not achieved and/or Additional factor X containing agents were required to restore haemostasis. * Unassessable -Efficacy was not possible to assess, or Additional factor X containing agents (excluding blood transfusions) were required before efficacy of FACTOR X could be assessed. |
| Number of Post Operative Bleeding Episodes (See Table Below) | End of surgery till end of study | Bleeding was assessed at least once each day by the investigator, more frequently if indicated by the severity of the operation or the subject's response. This included all bleeding episodes from the end of the surgical procedure until the subject was no longer at risk of bleeding due to surgery |
| Change of Haemoglobin From Pre-surgery Till End of Treatment | 2 hrs pre-operatively till end of treatment | The subject's haemoglobin was measured pre operatively, within 2 hours post operatively and at the End of Treatment Assessment. Changes in the subject's haemoglobin from pre to post operatively and from post operatively to the End of Treatment Assessment were assessed, taking into account the volume of fluid infused into the subject during the intervening periods, any blood transfusions in the intervening periods, the subject's haematocrit at the same time points and the subject's pre dose serum ferritin |
| Clinical Estimation of Volume of Blood Loss During Surgery | Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X. | As soon as possible after wound closure, the investigator estimated the volume of blood loss during surgery and made a clinical assessment against the volume of blood loss typically expected in a normal patient (i.e. one without a bleeding disorder and undergoing the same surgical procedure). The assessment may have been supported by a swab and pad count. The clinical assessment was rated as follows: * Blood loss less than expected * Blood loss as expected * Blood loss more than expected * Blood loss excessive (defined as more than twice the pre defined amount that would be expected in a normal patient for this type of surgery) |
| Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. | After wound closure | The investigator's estimation of the volume of blood loss during surgery compared to the volume of blood loss expected in patients without a bleeding disorder undergoing the same surgical procedure and reported as greater than, equal to or less than. |
| Requirement for Blood Transfusion | during and after surgery | Number of blood transfusions required (units of packed red blood cells or units of whole blood) or infusion of autologous red cells during and after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Per Infusion (IU/kg) | before surgery, during the post operative period | weight adjusted dose per infusion until a subject was no longer at risk of bleeding due to surgery |
| Incremental Recovery After Bolus Dose of FACTOR X | incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus | Incremental Recovery of FX:C after the Pre surgery Bolus Infusion The factor X increment is calculated by subtracting the pre-infusion factor X level from the post-dose value. Incremental recovery is calculated by FX increment (IU/dL)/ FX dose (IU/kg) |
Countries
Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment With FACTOR X Four patients underwent 4 major surgeries with active treatment (FACTOR X) | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Active Treatment With FACTOR X |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FX:C at diagnosis (IU/dL) | 7.5 IU/dL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United Kingdom | 2 participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change of Haemoglobin From Pre-surgery Till End of Treatment
The subject's haemoglobin was measured pre operatively, within 2 hours post operatively and at the End of Treatment Assessment. Changes in the subject's haemoglobin from pre to post operatively and from post operatively to the End of Treatment Assessment were assessed, taking into account the volume of fluid infused into the subject during the intervening periods, any blood transfusions in the intervening periods, the subject's haematocrit at the same time points and the subject's pre dose serum ferritin
Time frame: 2 hrs pre-operatively till end of treatment
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FACTOR X | Change of Haemoglobin From Pre-surgery Till End of Treatment | -36.0 g/L | Standard Deviation 26.17 |
Primary
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder.
The investigator's estimation of the volume of blood loss during surgery compared to the volume of blood loss expected in patients without a bleeding disorder undergoing the same surgical procedure and reported as greater than, equal to or less than.
Time frame: After wound closure
Population: All subjects treated with FACTOR X
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FACTOR X | Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. | More Than | 0 participants |
| FACTOR X | Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. | Less Than | 1 participants |
| FACTOR X | Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. | Equal to | 3 participants |
Primary
Clinical Estimation of Volume of Blood Loss During Surgery
As soon as possible after wound closure, the investigator estimated the volume of blood loss during surgery and made a clinical assessment against the volume of blood loss typically expected in a normal patient (i.e. one without a bleeding disorder and undergoing the same surgical procedure). The assessment may have been supported by a swab and pad count. The clinical assessment was rated as follows: * Blood loss less than expected * Blood loss as expected * Blood loss more than expected * Blood loss excessive (defined as more than twice the pre defined amount that would be expected in a normal patient for this type of surgery)
Time frame: Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X.
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FACTOR X | Clinical Estimation of Volume of Blood Loss During Surgery | 160.5 ml | Standard Deviation 168.49 |
Primary
Number of Participants With Degree of Bleeding Control Rated as Excellent.
Investigators made an overall assessment of FACTOR X in controlling bleeding at the End of Treatment Assessment. The degree of bleeding control was rated as excellent, good, poor or unassessable, in accordance with the following criteria listed below: * Excellent -Parameters were similar to those in subjects without a bleeding disorder. * Good -Parameters were inferior to those in subjects without a bleeding disorder, but no other factor X containing agents were required to restore haemostasis. * Poor - Blood loss was excessive (defined as more than twice the pre defined amount that would be expected in a subject without a bleeding disorder for this type of surgery) and/or Haemostasis was not achieved and/or Additional factor X containing agents were required to restore haemostasis. * Unassessable -Efficacy was not possible to assess, or Additional factor X containing agents (excluding blood transfusions) were required before efficacy of FACTOR X could be assessed.
Time frame: During and till end of treatment
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FACTOR X | Number of Participants With Degree of Bleeding Control Rated as Excellent. | 4 Participants |
Primary
Number of Post Operative Bleeding Episodes (See Table Below)
Bleeding was assessed at least once each day by the investigator, more frequently if indicated by the severity of the operation or the subject's response. This included all bleeding episodes from the end of the surgical procedure until the subject was no longer at risk of bleeding due to surgery
Time frame: End of surgery till end of study
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FACTOR X | Number of Post Operative Bleeding Episodes (See Table Below) | 0 number of bleeds |
Primary
Requirement for Blood Transfusion
Number of blood transfusions required (units of packed red blood cells or units of whole blood) or infusion of autologous red cells during and after surgery
Time frame: during and after surgery
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FACTOR X | Requirement for Blood Transfusion | 0 number of transfusions |
Secondary
Dose Per Infusion (IU/kg)
weight adjusted dose per infusion until a subject was no longer at risk of bleeding due to surgery
Time frame: before surgery, during the post operative period
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FACTOR X | Dose Per Infusion (IU/kg) | 16.14 IU/kg |
Secondary
Incremental Recovery After Bolus Dose of FACTOR X
Incremental Recovery of FX:C after the Pre surgery Bolus Infusion The factor X increment is calculated by subtracting the pre-infusion factor X level from the post-dose value. Incremental recovery is calculated by FX increment (IU/dL)/ FX dose (IU/kg)
Time frame: incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus
Population: The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FACTOR X | Incremental Recovery After Bolus Dose of FACTOR X | 2.14 IU/dL per IU/kg | Standard Deviation 0.224 |