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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
In case of major surgery, FVIII target level is ≥80% for major surgeries/ procedures and ≥50% for minor surgeries/ procedures.
Bleeding and Clotting Disorders Institute
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)
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)
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Peoria, Illinois, United States
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States
Case Western Reserve University
Cleveland, Ohio, United States
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
Sofia, Bulgaria
UMHATEM 'N.I. Pirogov', EAD
Sofia, Bulgaria
Hopital Maisonneuve-Rosemont d/b/a CIUSSS de l'Est-de-l'Île-de-Montréal
Montreal, Quebec, Canada
Universitaetsklinikum Bonn AoeR
Bonn, Germany
Zentrum für Hämostaseologie, Universitätsklinikum Leipzig AöR
Leipzig, Germany
Presidio Ospedaliero di Castelfranco Veneto
Castelfranco Veneto, Treviso, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, Italy
...and 14 more locations
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)