Safety & Efficacy of BPL's High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery

Study Overview
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Brief Summary
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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: A subjective overall assessment by the investigator of FACTOR X in the control of bleeding during surgery. The incidence of bleeding episodes during treatment with FACTOR X while the subject is at risk of post-operative bleeding, including location and duration. Incremental recovery of FX:C and FX:Ag after the pre-surgery bolus infusion. Assessment of FX:C and FX:Ag levels on each day post-surgery. 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. Assessment of the cumulative doses of FACTOR X as measured by FX:C (IU) administered to each subject to maintain haemostasis. 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
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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.

Official Title
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A Phase III Open, Multicentre Study to Investigate the Safety and Efficacy of BPL's High Purity FACTOR X in the Treatment of Factor X Deficient Subjects Undergoing Surgery

Conditions
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Factor X Deficiency

Intervention / Treatment
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* Biological: FACTOR X


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FACTOR X<br>Human Coagulation Factor X | Biological: FACTOR X<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X. | 
| 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. | After wound closure | 
| 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 | during and after surgery | 
| 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 | End of surgery till end of study | 
| 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 | 2 hrs pre-operatively till end of treatment | 
| 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. | During and till end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus | 
| Dose Per Infusion (IU/kg) | weight adjusted dose per infusion until a subject was no longer at risk of bleeding due to surgery | before surgery, during the post operative period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor X deficiency, surgery, Factor X deficiency subjects requiring surgery