Safety & Efficacy of BPL's High Purity FACTOR X in Treatm... | NCT01086852

Label	Type	Description	Intervention Names
FACTOR X	Experimental	Human Coagulation Factor X	Biological: FACTOR X

Name	Type	Description	Arm Group Labels	Other Names
FACTOR X	Biological	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.

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Tim Aldwinckle	Bio Products Laboratory	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University Of Texas Health Science Center, Gulf States Hemophilia and Thrombophilia Center 6655 Travis St		Houston	Texas	77030	United States

ID	Title	Description
FG000	Active Treatment With FACTOR X	Four subjects underwent 4 major surgeries with active treatment (FACTOR X)

ID	Title	Description
BG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	BG0004

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Geometric Mean

Standard Deviation

Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X.

ID	Title	Description
OG000	FACTOR X	Human Coagulation Factor X FACTOR 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.

Units	Counts
Participants	OG0004

Title

Denominators

Categories

Title	Measurements
	OG000160.5± 168.49

Secondary

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)

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Geometric Mean

Standard Deviation

IU/dL per IU/kg

incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus

ID	Title	Description
OG000	FACTOR X	Human Coagulation Factor X FACTOR 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.

Units	Counts
Participants	OG000

Primary

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.

All subjects treated with FACTOR X

Posted

Number

participants

After wound closure

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	OG000

Primary

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

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Number

number of transfusions

during and after surgery

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	OG000

Primary

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

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Number

number of bleeds

End of surgery till end of study

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	OG000

Primary

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

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Geometric Mean

Standard Deviation

g/L

2 hrs pre-operatively till end of treatment

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	OG000

Secondary

Dose Per Infusion (IU/kg)

weight adjusted dose per infusion until a subject was no longer at risk of bleeding due to surgery

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Median

Full Range

IU/kg

before surgery, during the post operative period

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts
Participants	OG0004

Primary

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.

The ITT population will be defined as all surgical procedures in which subjects were treated with at least one dose of FACTOR X and have undergone surgery.

Posted

Number

Participants

During and till end of treatment

ID	Title	Description
OG000	Active Treatment With FACTOR X	Four patients underwent 4 major surgeries with active treatment (FACTOR X)

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haematoma	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Post procedural discomfort	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0002 events1 affected4 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Incision site complication	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Haemoglobin decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Procedural pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected4 at risk
Oedema peripheral	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected4 at risk
Insomnia	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected4 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected4 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk
Herpes zoster	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected4 at risk

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Term
D004792	Enzyme Precursors
D045762	Enzymes and Coenzymes
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011498	Protein Precursors
D001685	Biological Factors