E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Factor X deficiency is lack of human coagulation factor X, one of the proteins in blood which enables blood to clot. This deficiency can cause patients to bleed spontaneously or following trauma. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
Female subjects of child-bearing potential with the exception of those entering the study for obstetric delivery 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 example oral contraceptives in combination with a barrier method, or IUDs (not copper IUDs) for the duration of the study, or for 8 days after the last dose of FACTOR X, whichever is longer. |
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E.4 | Principal 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 breastfeeding. Subjects participating in the study for obstetric delivery must be informed that they may not breastfeed during the study.
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 noncooperation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is blood loss during and after surgery; this is based upon the regulatory advice received during the preparation of this protocol. This assessment will be made by the investigator at the subject’s End-of-Treatment Assessment (after the last dose of FACTOR X).
The primary efficacy variable will be assessed by the following:
• Clinical estimation of volume of blood loss during to surgery
• Requirement for blood transfusion (units of packed red blood cells or units of whole blood) or infusion of autologous red cells during and after surgery
• Number and duration of post-operative bleeding episodes
• Measurements of haemoglobin pre-operatively, post-operatively, and at discharge.
The variables above will be combined in an overall assessment of blood loss during and after surgery against that typically expected in a normal patient (without a bleeding disorder) undergoing the same surgical procedure.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Assessment of 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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pre-operative, during and following surgery |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
India |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Per Section 10 of protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |