Hemophilia A
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of BAX 802 in males with congenital hemophilia A (CHA) with inhibitors who are undergoing major or minor elective surgical, dental, or other invasive procedures.
Interventions
BIOLOGICALAntihemophilic Factor (Recombinant), Porcine Sequence (BAX 802)
In case of major surgery, FVIII target level is ≥80% for major surgeries/ procedures and ≥50% for minor surgeries/ procedures.
Sponsors
Baxalta Innovations GmbH, now part of Shire
Baxalta now part of Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participant requires a major or minor elective surgical, dental or other invasive procedure 2. Participant is male and ≥ 12 to ≤ 75 years old at the time of screening 3. Participant has provided signed informed consent (and assent for adolescent participants, as applicable) in accordance with local regulatory requirements 4. Participant has severe (factor VIII (FVIII) level \< 1%) or moderately severe (FVIII level ≤ 2%) congenital hemophilia A (CHA) with inhibitors to human factor VIII (hFVIII) of ≥ 0.6 Bethesda units (BU), as tested at screening at the central laboratory 5. Participant is not currently receiving or has recently received (\< 30 days) immune tolerance induction (ITI) therapy 6. Participant has a Karnofsky performance score of ≥ 60 at screening 7. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3 at screening 8. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease. Positive serologies will be confirmed by PCR testing. 9. Participant is willing and able to comply with the requirements of the protocol.
Exclusion criteria
1. The participant requires emergency surgery 2. Severe chronic liver dysfunction or disease (e.g., ≥ 5 × upper limit of normal \[ULN\] alanine aminotransferase \[ALT\], as confirmed by central laboratory at screening or a documented prothrombin time/international normalized ratio \[PT/INR\] \> 1.5) 3. Clinically symptomatic renal disease (serum creatinine \> 2.0 mg/dL), as confirmed by central laboratory at screening 4. Anti-porcine factor VIII (pFVIII) inhibitor \> 10 BU prior to surgery 5. Platelet count \< 100,000/μL at screening 6. Participant has another active coagulation disorder, other than hemophilia A, as per the medical history 7. Planned use of α-interferon with or without ribavirin for HCV infected patients or planned use of a protease inhibitor for HIV infected patients. Patients currently taking any of these medications for ≥ 30 days are eligible 8. Known hypersensitivity to recombinant porcine factor VIII (rpFVIII), or hamster or murine proteins 9. Participant has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, fibrinolysis or disseminated intravascular coagulation (DIC) 10. Participant has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study 11. Participant is unable to tolerate quantity of blood to be drawn for protocol procedures 12. Participant is a family member or employee of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Surgeries With a Good or Excellent Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score | Day 1 up to discharge or Day 14 (whichever was earlier) | GHEA score consisted of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Overall Peri-operative Efficacy Assessment Scale. Scales 1 and 2 was performed by the operating surgeon on Day 1, and Scale 3 was performed by the investigator on Day 14. Each rating scale was based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). Total score ranged from 0 to 9, where scores evaluated as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). The scores of 3 individual ratings scales were added together to form a GHEA score. For a GHEA score of 7 to be rated excellent with no individual assessment scores less than (\<) 2 and at least 1 assessment score equal to (=) 3; otherwise a score of 7 was rated good. Percentage of Surgeries With a Good or Excellent response as measured by the GHEA score were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier) | Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and estimated volume of expected average blood loss during each operative period was reported. |
| Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier) | Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and expected maximum blood loss during each operative period was reported. |
| Percentage of Major Surgeries With Good or Excellent Hemostatic Score | Day 1 up to discharge or Day 14 (whichever was earlier) | Percentage of major surgeries with good or excellent hemostatic score was analyzed by GHEA score. It consisted of 3 individual ratings: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, (3) Postoperative Efficacy Assessment Scale. Ratings 1 and 2 was performed by the operating surgeon on Day 1, and Rating 3 was performed by the investigator on Day 14. Each rating scale was based on 4 point scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). The scores of each of the 3 individual ratings scales, was added together to form a GHEA score. Total score ranged from 0 to 9 where scores evaluated as excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). Hemostatic efficacy success was defined as excellent or good outcome for \>=70% of hemostatic efficacy assessments. Percentage of major surgeries with good or excellent hemostatic score were reported. |
| Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier) | Body-weight adjusted dose equals to amount infused/body-weight (kilogram \[kg\]), where amount infused as amount of drug infused (International Units \[IU\]) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Average daily weight-adjusted dose of BAX 802 per participant during each operative period was reported. |
| Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier) | Body-weight adjusted dose equals to amount infused/body-weight (kg), where amount infused as amount of drug infused (IU) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Total weight-adjusted dose of BAX 802 per participant during each operative period was reported. |
| Volume of Blood Products Transfused | From initiation of the surgery up to discharge or Day 14 (whichever came earlier) | The volume (in mL) of blood products transfused from initiation of the intervention to discharge or Day 14 (whichever came earlier) was reported. |
| Number of Participants With De Novo Inhibitors | Baseline up end of study (EOS) (up to 44 months) | De novo inhibitor was defined as a post-baseline inhibitor titer to FVIII (hFVIII or porcine factor VIII \[pFVIII\])of \>=0.6 Bethesda units per milliliter (BU/mL) given a baseline of \<0.6 BU/mL. Number of participants with de novo inhibitors were reported. |
| Number of Participants With Anamnestic Reactions | Baseline up to EOS (up to 44 months) | An anamnestic reaction was defined as an increase from a measurable baseline (\>0.6 BU/mL) in the inhibitor titer to FVIII (human or porcine) of \>=10 BU/mL. Number of participants with anamnestic reactions were reported. |
| Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier) | Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (in milliliter \[mL\]) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Actual blood loss, estimated volume of expected average blood loss and expected maximum blood loss during each operative period was reported. |
| Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII | Baseline up to EOS (up to 44 months) | The assessment of inhibitory antibodies (IgG and IgM) to hFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to hFVIII was determined using ELISA. Mean change from baseline in inhibitory and binding antibodies to hFVIII was reported. |
| Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins | Baseline up to EOS (up to 44 months) | The assessment of binding antibodies to BHK proteins was determined using ELISA. Clinical significance was judged by the investigator. Number of participants with clinically significant change from baseline in binding antibodies to BHK proteins were reported. |
| Number of Participants With Thromboembolic Events | Baseline up to EOS (up to 44 months) | Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream to plug another vessel. Number of participants with thromboembolic events was reported. |
| Number of Participants With Severe Allergic Reactions | Baseline up to EOS (up to 44 months) | Number of participants with severe allergic reaction (example: anaphylaxis) after administration of study drug were reported. |
| Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to EOS (up to 44 months) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment. TEAEs included both serious and non-serious TEAEs. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Sign | Baseline up to EOS (up to 44 months) | Vital sign parameters included: temperature, pulse rate, respiration rate, systolic and diastolic blood pressure. Any changes in vital signs which were deemed clinically significant was judged by the investigator. Number of participants with clinically significant change from baseline in vital signs were reported. |
| Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values | Baseline up to EOS (up to 44 months) | Clinical laboratory assessment included hematology and clinical chemistry. Any changes in clinical laboratory results which were deemed clinically significant was judged by the investigator. Number of participants with clinical significant change from baseline in clinical laboratory values were reported. |
| Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII | Baseline up to EOS (up to 44 months) | The assessment of inhibitory antibodies (immunoglobulin G \[IgG\] and immunoglobulin M \[IgM\]) to pFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to pFVIII was determined using validated enzyme-linked immunosorbent assays (ELISAs). Mean change from baseline in inhibitory and binding antibodies to pFVIII was reported. |
Countries
Bulgaria, Canada, Germany, Italy, Netherlands, Norway, Poland, Russia, South Africa, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
This study was conducted at 5 sites in Italy, Netherlands, Poland, Germany and Turkey. Study was initiated on 22 December 2016 and terminated on 22 January 2021.
Pre-assignment details
A total of 8 participants planned for Major Surgeries and Minor Surgeries received recombinant porcine factor VIII (rpFVIII) (BAX 802).
Participants by arm
| Arm | Count |
|---|---|
| Major Surgeries Male participants with CHA with inhibitors to hFVIII undergone major surgical invasive procedures initially received loading dose BAX 802 infusion, intravenously to maintain a minimum target FVIII level of \>=80% approximately 1 to 2 hours prior to the surgery. Subsequent dosing was based on participant's FVIII activity levels, body weight and investigator's clinical judgement. | 7 |
| Minor Surgeries Male participants with CHA with inhibitors to hFVIII undergone minor surgical invasive procedures initially received loading dose BAX 802 infusion, intravenously to maintain a minimum target FVIII level of \>=50% approximately 1 to 2 hours prior to the surgery. Subsequent dosing was based on participant's FVIII activity levels, body weight and investigator's clinical judgement. | 1 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 1 |
Baseline characteristics
| Characteristic | Minor Surgeries | Total | Major Surgeries |
|---|---|---|---|
| Age, Continuous | 58.0 years | 38.6 years STANDARD_DEVIATION 15.45 | 35.9 years STANDARD_DEVIATION 14.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 1 |
| other Total, other adverse events | 3 / 7 | 0 / 1 |
| serious Total, serious adverse events | 6 / 7 | 0 / 1 |
Outcome results
Primary
Percentage of Surgeries With a Good or Excellent Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score
GHEA score consisted of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Overall Peri-operative Efficacy Assessment Scale. Scales 1 and 2 was performed by the operating surgeon on Day 1, and Scale 3 was performed by the investigator on Day 14. Each rating scale was based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). Total score ranged from 0 to 9, where scores evaluated as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). The scores of 3 individual ratings scales were added together to form a GHEA score. For a GHEA score of 7 to be rated excellent with no individual assessment scores less than (\<) 2 and at least 1 assessment score equal to (=) 3; otherwise a score of 7 was rated good. Percentage of Surgeries With a Good or Excellent response as measured by the GHEA score were reported.
Time frame: Day 1 up to discharge or Day 14 (whichever was earlier)
Population: Full analysis set (FAS) comprised of all participants with at least one available hemostatic assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Major Surgeries | Percentage of Surgeries With a Good or Excellent Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score | GHEA rating: Good | 14.3 percentage of surgeries |
| Major Surgeries | Percentage of Surgeries With a Good or Excellent Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score | GHEA rating: Excellent | 71.4 percentage of surgeries |
Secondary
Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period
Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (in milliliter \[mL\]) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Actual blood loss, estimated volume of expected average blood loss and expected maximum blood loss during each operative period was reported.
Time frame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
Population: FAS comprised of all participants with at least one available hemostatic assessment. Here number analyzed were participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative Period: Actual Blood Loss | 141.1 milliliter (mL) | Standard Deviation 188.69 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative Period: Expected Average Blood Loss | 221.7 milliliter (mL) | Standard Deviation 286.76 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative Period: Expected Maximum Blood Loss | 414.7 milliliter (mL) | Standard Deviation 546.37 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Post-operative Period: Actual Blood Loss | 31.0 milliliter (mL) | Standard Deviation 66.56 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Post-operative Period: Expected Average Blood Loss | 171.4 milliliter (mL) | Standard Deviation 276.17 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Post-operative Period: Expected Maximum Blood Loss | 378.0 milliliter (mL) | Standard Deviation 570.94 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Peri-operative Period: Actual Blood Loss | 164.1 milliliter (mL) | Standard Deviation 215.15 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Peri-operative Period: Expected Average Blood Loss | 465.0 milliliter (mL) | Standard Deviation 744.85 |
| Major Surgeries | Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Peri-operative Period: Expected Maximum Blood Loss | 842.9 milliliter (mL) | Standard Deviation 1310.01 |
Secondary
Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period
Body-weight adjusted dose equals to amount infused/body-weight (kilogram \[kg\]), where amount infused as amount of drug infused (International Units \[IU\]) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Average daily weight-adjusted dose of BAX 802 per participant during each operative period was reported.
Time frame: Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)
Population: SAS comprised of all participants who received any amount of BAX 802. Here number analyzed were participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Major Surgeries | Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative | 162.471 International Units per kilogram (IU/kg) | Standard Deviation 125.7051 |
| Major Surgeries | Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Intra-operative | 76.083 International Units per kilogram (IU/kg) | Standard Deviation 35.1339 |
| Major Surgeries | Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Post-operative | 43.549 International Units per kilogram (IU/kg) | Standard Deviation 56.0039 |
| Minor Surgeries | Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative | 208.779 International Units per kilogram (IU/kg) | — |
Secondary
Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII
The assessment of inhibitory antibodies (IgG and IgM) to hFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to hFVIII was determined using ELISA. Mean change from baseline in inhibitory and binding antibodies to hFVIII was reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Major Surgeries | Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII | 198.67 BU/mL | Standard Deviation 317.254 |
| Minor Surgeries | Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII | -0.20 BU/mL | — |
Secondary
Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII
The assessment of inhibitory antibodies (immunoglobulin G \[IgG\] and immunoglobulin M \[IgM\]) to pFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to pFVIII was determined using validated enzyme-linked immunosorbent assays (ELISAs). Mean change from baseline in inhibitory and binding antibodies to pFVIII was reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Major Surgeries | Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII | 111.15 BU/mL | Standard Deviation 149.072 |
| Minor Surgeries | Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII | -0.20 BU/mL | — |
Secondary
Number of Participants With Anamnestic Reactions
An anamnestic reaction was defined as an increase from a measurable baseline (\>0.6 BU/mL) in the inhibitor titer to FVIII (human or porcine) of \>=10 BU/mL. Number of participants with anamnestic reactions were reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Major Surgeries | Number of Participants With Anamnestic Reactions | hFVIII | 5 Participants |
| Major Surgeries | Number of Participants With Anamnestic Reactions | pFVIII | 3 Participants |
| Minor Surgeries | Number of Participants With Anamnestic Reactions | hFVIII | 0 Participants |
| Minor Surgeries | Number of Participants With Anamnestic Reactions | pFVIII | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins
The assessment of binding antibodies to BHK proteins was determined using ELISA. Clinical significance was judged by the investigator. Number of participants with clinically significant change from baseline in binding antibodies to BHK proteins were reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Major Surgeries | Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins | 0 Participants |
| Minor Surgeries | Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
Clinical laboratory assessment included hematology and clinical chemistry. Any changes in clinical laboratory results which were deemed clinically significant was judged by the investigator. Number of participants with clinical significant change from baseline in clinical laboratory values were reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Major Surgeries | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values | 0 Participants |
| Minor Surgeries | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Sign
Vital sign parameters included: temperature, pulse rate, respiration rate, systolic and diastolic blood pressure. Any changes in vital signs which were deemed clinically significant was judged by the investigator. Number of participants with clinically significant change from baseline in vital signs were reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Major Surgeries | Number of Participants With Clinically Significant Change From Baseline in Vital Sign | 0 Participants |
| Minor Surgeries | Number of Participants With Clinically Significant Change From Baseline in Vital Sign | 0 Participants |
Secondary
Number of Participants With De Novo Inhibitors
De novo inhibitor was defined as a post-baseline inhibitor titer to FVIII (hFVIII or porcine factor VIII \[pFVIII\])of \>=0.6 Bethesda units per milliliter (BU/mL) given a baseline of \<0.6 BU/mL. Number of participants with de novo inhibitors were reported.
Time frame: Baseline up end of study (EOS) (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Major Surgeries | Number of Participants With De Novo Inhibitors | hFVIII | 0 Participants |
| Major Surgeries | Number of Participants With De Novo Inhibitors | pFVIII | 3 Participants |
| Minor Surgeries | Number of Participants With De Novo Inhibitors | hFVIII | 0 Participants |
| Minor Surgeries | Number of Participants With De Novo Inhibitors | pFVIII | 0 Participants |
Secondary
Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment. TEAEs included both serious and non-serious TEAEs.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Major Surgeries | Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | IP related TEAEs | 4 Participants |
| Major Surgeries | Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | IP related serious TEAEs | 4 Participants |
| Minor Surgeries | Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | IP related TEAEs | 0 Participants |
| Minor Surgeries | Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | IP related serious TEAEs | 0 Participants |
Secondary
Number of Participants With Severe Allergic Reactions
Number of participants with severe allergic reaction (example: anaphylaxis) after administration of study drug were reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Major Surgeries | Number of Participants With Severe Allergic Reactions | 0 Participants |
| Minor Surgeries | Number of Participants With Severe Allergic Reactions | 0 Participants |
Secondary
Number of Participants With Thromboembolic Events
Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream to plug another vessel. Number of participants with thromboembolic events was reported.
Time frame: Baseline up to EOS (up to 44 months)
Population: SAS comprised of all participants who received any amount of BAX 802.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Major Surgeries | Number of Participants With Thromboembolic Events | 0 Participants |
| Minor Surgeries | Number of Participants With Thromboembolic Events | 0 Participants |
Secondary
Percentage of Major Surgeries With Good or Excellent Hemostatic Score
Percentage of major surgeries with good or excellent hemostatic score was analyzed by GHEA score. It consisted of 3 individual ratings: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, (3) Postoperative Efficacy Assessment Scale. Ratings 1 and 2 was performed by the operating surgeon on Day 1, and Rating 3 was performed by the investigator on Day 14. Each rating scale was based on 4 point scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). The scores of each of the 3 individual ratings scales, was added together to form a GHEA score. Total score ranged from 0 to 9 where scores evaluated as excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). Hemostatic efficacy success was defined as excellent or good outcome for \>=70% of hemostatic efficacy assessments. Percentage of major surgeries with good or excellent hemostatic score were reported.
Time frame: Day 1 up to discharge or Day 14 (whichever was earlier)
Population: FAS comprised of all participants with at least one available hemostatic assessment. As planned, this outcome measure was only analyzed for major surgeries. There were 7 participants analyzed for major surgeries and all the 7 participants underwent 7 surgeries.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Major Surgeries | Percentage of Major Surgeries With Good or Excellent Hemostatic Score | 85.7 percentage of surgeries |
Secondary
Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period
Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and estimated volume of expected average blood loss during each operative period was reported.
Time frame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
Population: FAS comprised of all participants with at least one available hemostatic assessment. Here number analyzed were participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Major Surgeries | Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative Period | 0.970 ratio | Standard Deviation 0.9486 |
| Major Surgeries | Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Post-operative Period | 0.150 ratio | Standard Deviation 0.2236 |
| Major Surgeries | Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Peri-operative Period | 0.545 ratio | Standard Deviation 0.3448 |
Secondary
Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period
Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and expected maximum blood loss during each operative period was reported.
Time frame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
Population: FAS comprised of all participants with at least one available hemostatic assessment. Here number analyzed were participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Major Surgeries | Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Intra-operative Period | 0.555 ratio | Standard Deviation 0.6517 |
| Major Surgeries | Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Post-operative Period | 0.058 ratio | Standard Deviation 0.0846 |
| Major Surgeries | Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period | Peri-operative Period | 0.306 ratio | Standard Deviation 0.1962 |
Secondary
Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period
Body-weight adjusted dose equals to amount infused/body-weight (kg), where amount infused as amount of drug infused (IU) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Total weight-adjusted dose of BAX 802 per participant during each operative period was reported.
Time frame: Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)
Population: SAS comprised of all participants who received any amount of BAX 802. Here number analyzed were participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Major Surgeries | Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative | 162.471 IU/kg | Standard Deviation 125.7051 |
| Major Surgeries | Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Intra-operative | 76.083 IU/kg | Standard Deviation 35.1339 |
| Major Surgeries | Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Post-operative | 625.520 IU/kg | Standard Deviation 399.4913 |
| Minor Surgeries | Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period | Pre-operative | 208.779 IU/kg | — |
Secondary
Volume of Blood Products Transfused
The volume (in mL) of blood products transfused from initiation of the intervention to discharge or Day 14 (whichever came earlier) was reported.
Time frame: From initiation of the surgery up to discharge or Day 14 (whichever came earlier)
Population: FAS comprised of all participants with at least one available hemostatic assessment. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Major Surgeries | Volume of Blood Products Transfused | 950.0 mL | Standard Deviation 70.71 |