Trial Outcomes & Findings for Safety & Efficacy of BPL's High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery (NCT NCT01086852)

Last Updated: 2019-02-05

Results Overview

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)

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

4 participants

Primary outcome timeframe

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

Results posted on

2019-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	Active Treatment With FACTOR X Four subjects underwent 4 major surgeries with active treatment (FACTOR X)
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Treatment With FACTOR X n=4 Participants Four patients underwent 4 major surgeries with active treatment (FACTOR X)
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Age, Continuous	57 years n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	4 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	2 participants n=99 Participants
Region of Enrollment United Kingdom	2 participants n=99 Participants
FX:C at diagnosis (IU/dL)	7.5 IU/dL n=99 Participants

PRIMARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Clinical Estimation of Volume of Blood Loss During Surgery	160.5 ml Standard Deviation 168.49

PRIMARY outcome

Timeframe: After wound closure

Population: All subjects treated with FACTOR X

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.

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. Less Than	1 participants
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. More Than	0 participants
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder. Equal to	3 participants

PRIMARY outcome

Timeframe: during and after surgery

Population: 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.

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

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Requirement for Blood Transfusion	0 number of transfusions

PRIMARY outcome

Timeframe: End of surgery till end of study

Population: 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.

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

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Number of Post Operative Bleeding Episodes (See Table Below)	0 number of bleeds

PRIMARY outcome

Timeframe: 2 hrs pre-operatively till end of treatment

Population: 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.

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

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Change of Haemoglobin From Pre-surgery Till End of Treatment	-36.0 g/L Standard Deviation 26.17

PRIMARY outcome

Timeframe: During and till end of treatment

Population: 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.

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.

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Number of Participants With Degree of Bleeding Control Rated as Excellent.	4 Participants

SECONDARY outcome

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

Population: 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.

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)

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Incremental Recovery After Bolus Dose of FACTOR X	2.14 IU/dL per IU/kg Standard Deviation 0.224

SECONDARY outcome

Timeframe: before surgery, during the post operative period

Population: 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.

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

Outcome measures

Outcome measures
Measure	FACTOR X n=4 Participants 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.
Dose Per Infusion (IU/kg)	16.14 IU/kg Interval 10.13 to 22.3

Adverse Events

FACTOR X

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	FACTOR X n=4 participants at risk 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.
Vascular disorders Haematoma	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Injury, poisoning and procedural complications Post procedural discomfort	25.0% 1/4 • Number of events 2 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Injury, poisoning and procedural complications Contusion	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Injury, poisoning and procedural complications Incision site complication	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Investigations Haemoglobin decreased	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
General disorders Procedural pain	50.0% 2/4 • Number of events 2 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
General disorders Oedema peripheral	50.0% 2/4 • Number of events 2 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Psychiatric disorders Insomnia	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Gastrointestinal disorders Constipation	75.0% 3/4 • Number of events 3 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Gastrointestinal disorders Dyspepsia	75.0% 3/4 • Number of events 3 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Skin and subcutaneous tissue disorders Ecchymosis	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Metabolism and nutrition disorders Hyperglycaemia	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Metabolism and nutrition disorders Hypokalaemia	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Metabolism and nutrition disorders Hypomagnesaemia	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed
Infections and infestations Herpes zoster	25.0% 1/4 • Number of events 1 • Adverse events were documented from the date the Informed Consent Form was signed until the end of the subject's participation in the study Treatment-emergent AEs are defined as AEs occurring or worsening after the start (date and time) of the first study treatment until End of Treatment Assessment or follow-up safety assessment (28 days after the last dose of FACTOR X) if performed

Additional Information

Miranda Norton

Bio Products Laboratory

Phone: 020 8 957 2661

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60