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TerminatedNCT01086852Ten03Updated Feb 5, 2019Results posted

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

A Phase 3 interventional study of FACTOR X in Factor X Deficiency, sponsored by Bio Products Laboratory. Terminated at 7 sites in 4 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2019-02-05.

Sponsored by Bio Products Laboratory · Phase 3, Interventional, and Treatment

Why this study was terminated
Closed early due to difficulties in enrolling the target number of 10 surgical procedures.
Phase
Phase 3
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
12 Years and older
Sex
All
01

Study 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.
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.

02

Conditions studied

  • Factor X Deficiency

Keywords

  • Factor X deficiency
  • surgery
  • Factor X deficiency subjects requiring surgery
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    FACTOR X

    Human Coagulation Factor X

    Biological: FACTOR X

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.

05

What researchers measure

Primary outcomes

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

Secondary outcomes

  1. 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

  2. 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

06

Results

Posted Jul 3, 2015
Limitations and caveats
none reported

Participant flow

Participant flow — Overall Study
MilestoneActive Treatment With FACTOR X
Started4
Completed4
Not completed0

Outcome measures

PrimaryClinical 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.
Reported as:
Geometric mean · ml
Clinical Estimation of Volume of Blood Loss During Surgery
mlFACTOR X
Clinical Estimation of Volume of Blood Loss During Surgery160.5 ± 168.49
SecondaryIncremental 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
Reported as:
Geometric mean · IU/dL per IU/kg
Incremental Recovery After Bolus Dose of FACTOR X
IU/dL per IU/kgFACTOR X
Incremental Recovery After Bolus Dose of FACTOR X2.14 ± 0.224
PrimaryClinical 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
Reported as:
Number · participants
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder.
participantsActive Treatment With FACTOR X
Less Than1
More Than0
Equal to3
PrimaryRequirement 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
Reported as:
Number · number of transfusions
Requirement for Blood Transfusion
number of transfusionsActive Treatment With FACTOR X
Requirement for Blood Transfusion0
PrimaryNumber 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
Reported as:
Number · number of bleeds
Number of Post Operative Bleeding Episodes (See Table Below)
number of bleedsActive Treatment With FACTOR X
Number of Post Operative Bleeding Episodes (See Table Below)0
PrimaryChange 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
Reported as:
Geometric mean · g/L
Change of Haemoglobin From Pre-surgery Till End of Treatment
g/LActive Treatment With FACTOR X
Change of Haemoglobin From Pre-surgery Till End of Treatment-36.0 ± 26.17
SecondaryDose 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
Reported as:
Median · IU/kg
Dose Per Infusion (IU/kg)
IU/kgActive Treatment With FACTOR X
Dose Per Infusion (IU/kg)16.14 (10.13 to 22.30)
PrimaryNumber 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
Reported as:
Number · Participants
Number of Participants With Degree of Bleeding Control Rated as Excellent.
ParticipantsActive Treatment With FACTOR X
Number of Participants With Degree of Bleeding Control Rated as Excellent.4

Adverse events

Collected over Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
FACTOR X—0/4 (0%)4/4 (100%)
Most frequent other events
Showing 10 of 19
Most frequent other events
EventFACTOR X
ConstipationGastrointestinal disorders3/4
DyspepsiaGastrointestinal disorders3/4
Procedural painGeneral disorders2/4
Oedema peripheralGeneral disorders2/4
HaematomaVascular disorders1/4
Post procedural discomfortInjury, poisoning and procedural complications1/4
ContusionInjury, poisoning and procedural complications1/4
Incision site complicationInjury, poisoning and procedural complications1/4
Haemoglobin decreasedInvestigations1/4
Oropharyngeal painRespiratory, thoracic and mediastinal disorders1/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Active Treatment With FACTOR X
<=18 years0
Between 18 and 65 years4
>=65 years0
Age, Continuous
Age, Continuous(years)Active Treatment With FACTOR X
Median57 (55 to 59)
Sex: Female, Male
Sex: Female, Male(Participants)Active Treatment With FACTOR X
Female0
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Active Treatment With FACTOR X
Hispanic or Latino0
Not Hispanic or Latino4
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Active Treatment With FACTOR X
American Indian or Alaska Native0
Asian2
Native Hawaiian or Other Pacific Islander0
Black or African American0
White2
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Active Treatment With FACTOR X
United States2
United Kingdom2
FX:C at diagnosis (IU/dL)
FX:C at diagnosis (IU/dL)(IU/dL)Active Treatment With FACTOR X
Median7.5 (7 to 8)
07

Study locations

7 sites
  • University Of Texas Health Science Center, Gulf States Hemophilia and Thrombophilia Center 6655 Travis St
    Houston, Texas 77030, United States
  • Unidad Coagulopatías, Congenitas, Edificio Dotacional, 1ra Planta Hospital Universito La Paz
    Madrid, 28046, Spain
  • Ege University School of Medicine, Departmant of Pediatric Hematology
    Bornova, Izmir 35100, Turkey
  • Istanbul University Cerrahpasa Medicine Faculty Department of Pediatric Hematology
    Istanbul, 34098, Turkey
  • Department of Hematology, Royal Cornwall Hospital,
    Truro, Cornwall TR1 3LJ, United Kingdom
  • The Katherine Dormandy Haemophilia Centre and Thrombosis Unit, The Royal Free Hospital,Pond Street
    Hampstead, London NW3 2QG, United Kingdom
  • Hammersmith Hospital
    London, W12 0NN, United Kingdom
08

Registry details

Key details

Study ID
NCT01086852
Lead sponsor
Bio Products Laboratory
Responsible party
Sponsor
First posted
Mar 15, 2010
Start date
Mar 2011
Primary completion
Jan 2014
Completion
Jan 2014
Results posted
Jul 3, 2015
Last update
Feb 5, 2019

Study contacts

Tim Aldwinckle
principal investigator · Bio Products Laboratory

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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