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

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

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.

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.

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.