Factor X DeficiencyPhase 3Ten03NCT01086852
Safety & Efficacy of BPL's High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery
A Phase 3 study testing FACTOR X in people with Factor X Deficiency, run by Bio Products Laboratory at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Factor X Deficiency
- What is being tested?
- FACTOR X
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Mar 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United Kingdom3 sites
The Katherine Dormandy Haemophilia Centre and Thrombosis Unit, The Royal Free Hospital,Pond Street
Hampstead, London, NW3 2QG
Hammersmith Hospital
London, W12 0NN
Department of Hematology, Royal Cornwall Hospital,
Truro, Cornwall, TR1 3LJ
Turkey (Türkiye)2 sites
Ege University School of Medicine, Departmant of Pediatric Hematology
Bornova, İzmir, 35100
Istanbul University Cerrahpasa Medicine Faculty Department of Pediatric Hematology
Istanbul, 34098
United States1 site
University Of Texas Health Science Center, Gulf States Hemophilia and Thrombophilia Center 6655 Travis St
Houston, Texas, 77030
Spain1 site
Unidad Coagulopatías, Congenitas, Edificio Dotacional, 1ra Planta Hospital Universito La Paz
Madrid, 28046
About this study
Official title: 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:
- 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.
Read the 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.
- Conditions
- Factor X Deficiency
- Being tested
- FACTOR X
- Keywords
- Factor X deficiency, surgery, Factor X deficiency subjects requiring surgery
- Medical subject headings
- Factor X Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FACTOR XBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| FACTOR X | Experimental | Human Coagulation Factor X Receives: Biological: FACTOR X |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: During and till end of treatment
Secondary outcomes (2)
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)
Measured: 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
Measured: before surgery, during the post operative period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2010 (estimated)
- Study startMar 2011
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Closed early due to difficulties in enrolling the target number of 10 surgical procedures.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Factor X DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio Products Laboratory
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Aldwinckle, Principal investigator, Bio Products Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01086852
- Sponsor's protocol ID
- Ten03
- Acronym
- Ten03
- Status last verified
- Jan 2019
- First submitted
- 10 Nov 2009
- Last updated
- 5 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01086852
- Acronym / sponsor ID
- Ten03 / Ten03
- Conditions
- Factor X Deficiency
- Keywords
- Factor X deficiency, surgery, Factor X deficiency subjects requiring surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed early due to difficulties in enrolling the target number of 10 surgical procedures.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Bio Products LaboratoryUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 15 Mar 2010 (estimated)
- Results
- Posted 3 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FACTOR X | Experimental | Biological: FACTOR XHuman Coagulation Factor X |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FACTOR XPresurgery 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. | Biological | FACTOR X |
Primary outcome
Clinical Estimation of Volume of Blood Loss During Surgery
Time frame: 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.
Time frame: 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
Time frame: 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
Number of Post Operative Bleeding Episodes (See Table Below)
Time frame: 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
Time frame: 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
Number of Participants With Degree of Bleeding Control Rated as Excellent.
Time frame: 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.
2 secondary outcomes
Incremental Recovery After Bolus Dose of FACTOR X
Time frame: incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus
Dose Per Infusion (IU/kg)
Time frame: before surgery, during the post operative period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Aldwinckle principal investigator
Bio Products Laboratory
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FACTOR X in people with Factor X Deficiency, run by Bio Products Laboratory at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Turkey (Türkiye), United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Estimation of Volume of Blood Loss During Surgery (time frame: Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2019.