Back to resultsPhase 3 Efficacy and Safety Study of BAX 855 in Severe Hemophilia A Patients Undergoing Surgical Procedures
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
PEGylated Recombinant factor VIII (rFVIII)
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria:
- Participant requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy).
- Participant and/or legal representative has/have provided signed informed consent.
- Participant has severe hemophilia A (Factor VIII (FVIII) level <1%) as confirmed by the central lab at screening or a documented FVIII activity level <1%.
- Participant was previously treated with FVIII concentrates with ≥150 documented exposure days (EDs).
- Participant is currently receiving prophylaxis or on-demand therapy with FVIII concentrate.
- Participant has a Karnofsky performance score of ≥60 at screening.
- Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥200 cells/mm^3, as confirmed by central laboratory at screening.
- Participant is Hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis as assessed by the investigator.
- Participant is willing and able to comply with the requirements of the study protocol.
Exclusion Criteria:
- Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Unit (BU) using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay).
- History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
- Participant has a platelet count <100 x 10^9/L, as confirmed by central laboratory at screening.
- Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
- Participant has severe chronic hepatic dysfunction (eg ≥5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by the central laboratory at screening, or a documented International Normalized Ratio (INR) > 1.5).
- Participant has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG.
- Participant is currently using or has recently (< 30 days) used pegylated drugs (other than BAX 855) prior to study participation or is scheduled to use such drugs during trial participation.
- Participant is currently participating in another clinical drug (other than BAX 855) or device study or use of another investigational product or device within 30 days prior to study entry.
- Participant has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A.
- Participant is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (eg, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy.
- Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
Sites / Locations
- University of Florida College of Medicine
- Bleeding and Clotting Disorders Institute
- University of Louisville
- Children's Mercy Hospitals & Clinics
- Cincinnati Children's Hospital Medical Center
- Penn State Milton S. Hershey Medical Center
- University of Utah Health Sciences Center
- University of Washington
- SHAT of Oncohaematology Diseases
- MHAT 'Sv. Marina', EAD
- Vilnius University Hospital Santariskiu Clinics, Public Institution
- Academisch Medisch Centrum
- FSHI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"
- Hospital Universitari Son Espases
- Complejo Hospitalario Universitario A Coruña
- Hospital Regional Universitario de Malaga
- Hospital Universitari i Politecnic La Fe
- Universitaetsspital Zuerich
- SI Institute of Blood Pathology and Transfusion Medicine of AMSU
- Royal Free Hospital
- Great Ormond Street Hospital for Children
- Royal Manchester Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BAX855
Arm Description
Pre-operative loading dose: Single loading dose, pre-surgery administered based on each study participant's individual PK results as well as target trough level for type and character of surgery, dental or invasive procedure being performed. In general, major surgery will target an 80-150% FVIII trough level, and minor surgery will target an initial 30-100% FVIII trough level. Intra-operative and post-operative dosing of BAX855 must be based on pre-dosage measurements of FVIII and the type and character of the surgery performed.
Outcomes
Primary Outcome Measures
Global Hemostatic Efficacy Assessment Score (GHEA) - Composed of 3 Individual Ratings
GHEA=Sum of 1-3 ratings: Excellent: 7-9 (no category <2), Good: 5-7 (no category <1), Fair: 3-4 (no category <1) 1. Intraoperative and 2. Postoperative (postoperative day 1) hemostatic efficacy assessments: Excellent=3: Blood Loss (BL) ≤ than expected for procedure type in non-hemophilic population (NHP) (≤100%), Good=2: BL ≤50% more than expect. for procedure type in NHP (101-150%), Fair=1: BL >50% more than expect. for procedure type in NHP (>150%), None=0: Significant bleeding-requiring rescue therapy (RT) 3. Perioperative hemostatic efficacy assessment (day 14 or discharge, whatever is first): Excellent=3: BL and required blood transfusions (BT) less than or similar (≤100%) to that expected for procedure type in NHP, Good=2: BL ≤50% more (101-150%) and BT less than or similar to that expected for procedure type in NHP, Fair=1: BL >50% more (>150%) and BT greater than expected in NHP, None=0: Significant bleeding-requiring RT, BT substantially greater than expected in NHP
Secondary Outcome Measures
Intraoperative Blood Loss
Actual intraoperative blood loss was assessed at the end of surgery and was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected intraoperative blood loss was predicted preoperatively by the investigator/surgeon.
Postoperative Blood Loss
Actual post-operative blood loss assessed at postoperative day 1 was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected postoperative blood loss was predicted pre-operatively by the investigator/surgeon.
Overall Perioperative Blood Loss
Actual overall perioperative blood loss (assessed at the end of surgery, at postoperative day 1 and until discharge or day 14 - whichever is first) was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected perioperative blood loss was predicted pre-operatively by the investigator/surgeon.
Transfusion Requirements
Volume of blood, red blood cells, platelets, and other blood products transfused. Only packed red blood cells were transfused in this study.
Occurrence of Bleeding Episodes and Additional Need for Surgical Intervention
Any clinically relevant bleeding episodes (as assessed by the investigator) as well as the need for any further surgical interventions were recorded. If the subject had not resumed his previous treatment after discharge, the occurrence and treatment of bleeding episodes were recorded in the subject's diary.
Consumption of BAX855
Daily and total weight-adjusted consumption of BAX855 per subject.
Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞)
Following at least a 72 hour washout period a single dose of BAX855 was administered. The PK profiles was used to guide dosing and dosing frequency during the perioperative time period. The area under the plasma concentration/time curve from time 0 to infinity (AUC 0-inf) and the area under the first movement curve from time 0 to infinity (AUMC 0-inf) was calculated as the sum of AUC and AUMC from time 0 to the time of the last quantifiable concentration plus a tail area correction calculated as Ct/λz and Ct/λz(t+1/λz), respectively, where Ct is the last quantifiable concentration, t is the time of last quantifiable concentration and λz is the terminal or disposition rate constant. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours Post-infusion (AUC0-96h)
Following at least a 72 hour (h) washout period a single dose of BAX855 will be administered. The PK profiles was used to guide dosing and dosing frequency during the perioperative time period. The area under the plasma concentration/time curve from time 0 to 96 hours postinfusion (AUC 0-96h) was computed using the linear trapezoidal rule. For the calculation of AUC 0-96h the levels at 96 hours were linearly interpolated/extrapolated from the 2 nearest sampling time points. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Pharmacokinetics (PK) - Terminal Half-life (T1/2)
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Terminal or disposition half-life (HL) was calculated as log e(2)/λz where the terminal or disposition rate constant (λz) was estimated as the slope of a log-linear least squares regression model. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Pharmacokinetics (PK) - Mean Residence Time (MRT)
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Mean residence time (MRT) was calculated as total area under the moment curve divided by the total area under the curve. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Pharmacokinetics (PK) - Clearance (CL)
Following a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Systemic clearance (CL) was calculated as the dose in IU/kg divided by the total AUC. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results. h = hours
Pharmacokinetics (PK) - Apparent Volume of Distribution at Steady State (Vss)
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Apparent steady state volume of distribution (Vss) was calculated as dose multiplied with AUMC(0-inf) divided by AUC(0-inf) to square. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Pharmacokinetics (PK) - Incremental Recovery(IR)
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Incremental recovery (IR) was calculated as C post infusion minus C pre-infusion divided by the dose. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Development of Inhibitory Antibodies to Factor VIII (FVIII)
Immunogenicity assessment using FVIII inhibitor by Nijmegen method. A 72-hour washout period is required prior to immunogenicity tests.
Development of Treatment Emerging Binding Antibodies to Factor VIII (FVIII), Treatment Emergent Binding Antibodies to PEGylated Recombinant FVIII (BX855), and Treatment Emerging Binding Antibodies to Polyethylene Glycol (PEG)
A 72-hour washout period is required prior to immunogenicity tests.
Development of Treatment Emerging Anti-chinese Hamster Ovary (CHO) Antibodies
A 72-hour washout period is required prior to immunogenicity tests.
Occurrence of Thrombotic Events
Incidence of Severe Allergic Reactions (e.g. Anaphylaxis)
Other Investigational Product (IP) - Related Adverse Events
Clinically Significant Changes in Vital Signs - Body Temperature
Changes in body temperature were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Clinically Significant Changes in Vital Signs - Systolic and Diastolic Blood Pressure (BP)
Changes in systolic and diastolic blood pressure (mmHg) were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Clinically Significant Changes in Vital Signs - Respiratory Rate
Changes in Respiratory rate were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Clinically Significant Changes in Vital Signs - Pulse Rate
Changes in the pulse rate (beats/minute) were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Clinically Significant Changes in Routine Laboratory Parameters- Hematology and Chemistry
Changes in clinical chemistry and hematology parameters from a normal or abnormal not clinically significant (ncs) result at screening to an abnormal and clinically significant (cs) result at the end of study assessment (EOS) are listed. Changes did occur in the following laboratory parameters: Alanine Aminotransferase (ALT) (U/L), Hemoglobin (g/L), Hematocrit, Erythrocytes(TI/L), Eosinophils/Leucocytes.
Full Information
NCT ID
NCT01913405
First Posted
June 27, 2013
Last Updated
April 30, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT01913405
Brief Title
Phase 3 Efficacy and Safety Study of BAX 855 in Severe Hemophilia A Patients Undergoing Surgical Procedures
Official Title
A Phase 3, Multi-Center, Open Label Study of Efficacy and Safety of PEGylated rFVIII (BAX 855) in Previously Treated Patients With Severe Hemophilia A Undergoing Surgical or Other Invasive Procedures
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
December 20, 2013 (Actual)
Primary Completion Date
September 23, 2016 (Actual)
Study Completion Date
September 23, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to evaluate the efficacy and safety of BAX 855 in severe hemophilia A previously treated (PTP) males, 12 to 65 years of age who are undergoing elective surgical or other invasive procedures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BAX855
Arm Type
Experimental
Arm Description
Pre-operative loading dose: Single loading dose, pre-surgery administered based on each study participant's individual PK results as well as target trough level for type and character of surgery, dental or invasive procedure being performed. In general, major surgery will target an 80-150% FVIII trough level, and minor surgery will target an initial 30-100% FVIII trough level.
Intra-operative and post-operative dosing of BAX855 must be based on pre-dosage measurements of FVIII and the type and character of the surgery performed.
Intervention Type
Biological
Intervention Name(s)
PEGylated Recombinant factor VIII (rFVIII)
Other Intervention Name(s)
BAX 855, ADYNOVATE
Intervention Description
Lyophilized powder and solvent for solution for injection
Primary Outcome Measure Information:
Title
Global Hemostatic Efficacy Assessment Score (GHEA) - Composed of 3 Individual Ratings
Description
GHEA=Sum of 1-3 ratings: Excellent: 7-9 (no category <2), Good: 5-7 (no category <1), Fair: 3-4 (no category <1) 1. Intraoperative and 2. Postoperative (postoperative day 1) hemostatic efficacy assessments: Excellent=3: Blood Loss (BL) ≤ than expected for procedure type in non-hemophilic population (NHP) (≤100%), Good=2: BL ≤50% more than expect. for procedure type in NHP (101-150%), Fair=1: BL >50% more than expect. for procedure type in NHP (>150%), None=0: Significant bleeding-requiring rescue therapy (RT) 3. Perioperative hemostatic efficacy assessment (day 14 or discharge, whatever is first): Excellent=3: BL and required blood transfusions (BT) less than or similar (≤100%) to that expected for procedure type in NHP, Good=2: BL ≤50% more (101-150%) and BT less than or similar to that expected for procedure type in NHP, Fair=1: BL >50% more (>150%) and BT greater than expected in NHP, None=0: Significant bleeding-requiring RT, BT substantially greater than expected in NHP
Time Frame
Hemostatic efficacy assessments were performed intraoperatively, postoperatively on day 1 (approximately 24 hours after surgery) and perioperatively at day 14 or discharge (whichever was first).
Secondary Outcome Measure Information:
Title
Intraoperative Blood Loss
Description
Actual intraoperative blood loss was assessed at the end of surgery and was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected intraoperative blood loss was predicted preoperatively by the investigator/surgeon.
Time Frame
From initiation of surgery until end of surgery.
Title
Postoperative Blood Loss
Description
Actual post-operative blood loss assessed at postoperative day 1 was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected postoperative blood loss was predicted pre-operatively by the investigator/surgeon.
Time Frame
From completion of surgery until 24 hours after surgery.
Title
Overall Perioperative Blood Loss
Description
Actual overall perioperative blood loss (assessed at the end of surgery, at postoperative day 1 and until discharge or day 14 - whichever is first) was compared to the estimated volume of expected average and maximum blood loss in a hemostatically normal individual of the same sex, age and stature as the study participant. Expected perioperative blood loss was predicted pre-operatively by the investigator/surgeon.
Time Frame
From start of surgery until discharge or day 14, whichever occurred first.
Title
Transfusion Requirements
Description
Volume of blood, red blood cells, platelets, and other blood products transfused. Only packed red blood cells were transfused in this study.
Time Frame
From initiation of the surgery to 24 hours after completion of the surgery.
Title
Occurrence of Bleeding Episodes and Additional Need for Surgical Intervention
Description
Any clinically relevant bleeding episodes (as assessed by the investigator) as well as the need for any further surgical interventions were recorded. If the subject had not resumed his previous treatment after discharge, the occurrence and treatment of bleeding episodes were recorded in the subject's diary.
Time Frame
Intra- and post-operative period, until the last intensified treatment after hospital discharge (minor surgery 1-3 days, major surgery average approximately 2 weeks)
Title
Consumption of BAX855
Description
Daily and total weight-adjusted consumption of BAX855 per subject.
Time Frame
From initial loading dose until discharge for daily weight-adjusted dose and from first infusion (PK/IR) until end of study for total weight-adjusted dose.
Title
Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞)
Description
Following at least a 72 hour washout period a single dose of BAX855 was administered. The PK profiles was used to guide dosing and dosing frequency during the perioperative time period. The area under the plasma concentration/time curve from time 0 to infinity (AUC 0-inf) and the area under the first movement curve from time 0 to infinity (AUMC 0-inf) was calculated as the sum of AUC and AUMC from time 0 to the time of the last quantifiable concentration plus a tail area correction calculated as Ct/λz and Ct/λz(t+1/λz), respectively, where Ct is the last quantifiable concentration, t is the time of last quantifiable concentration and λz is the terminal or disposition rate constant. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours Post-infusion (AUC0-96h)
Description
Following at least a 72 hour (h) washout period a single dose of BAX855 will be administered. The PK profiles was used to guide dosing and dosing frequency during the perioperative time period. The area under the plasma concentration/time curve from time 0 to 96 hours postinfusion (AUC 0-96h) was computed using the linear trapezoidal rule. For the calculation of AUC 0-96h the levels at 96 hours were linearly interpolated/extrapolated from the 2 nearest sampling time points. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Terminal Half-life (T1/2)
Description
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Terminal or disposition half-life (HL) was calculated as log e(2)/λz where the terminal or disposition rate constant (λz) was estimated as the slope of a log-linear least squares regression model. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Mean Residence Time (MRT)
Description
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Mean residence time (MRT) was calculated as total area under the moment curve divided by the total area under the curve. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Clearance (CL)
Description
Following a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Systemic clearance (CL) was calculated as the dose in IU/kg divided by the total AUC. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results. h = hours
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Apparent Volume of Distribution at Steady State (Vss)
Description
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Apparent steady state volume of distribution (Vss) was calculated as dose multiplied with AUMC(0-inf) divided by AUC(0-inf) to square. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Pharmacokinetics (PK) - Incremental Recovery(IR)
Description
Following at least a 72 hour washout period a single dose of BAX855 will be administered. The PK profiles will be used to guide dosing and dosing frequency during the perioperative time period. Incremental recovery (IR) was calculated as C post infusion minus C pre-infusion divided by the dose. Main analysis was done on the one-stage clotting assay results, supportive analysis was done on the chromogenic assay results.
Time Frame
PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.
Title
Development of Inhibitory Antibodies to Factor VIII (FVIII)
Description
Immunogenicity assessment using FVIII inhibitor by Nijmegen method. A 72-hour washout period is required prior to immunogenicity tests.
Time Frame
Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).
Title
Development of Treatment Emerging Binding Antibodies to Factor VIII (FVIII), Treatment Emergent Binding Antibodies to PEGylated Recombinant FVIII (BX855), and Treatment Emerging Binding Antibodies to Polyethylene Glycol (PEG)
Description
A 72-hour washout period is required prior to immunogenicity tests.
Time Frame
Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).
Title
Development of Treatment Emerging Anti-chinese Hamster Ovary (CHO) Antibodies
Description
A 72-hour washout period is required prior to immunogenicity tests.
Time Frame
Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).
Title
Occurrence of Thrombotic Events
Time Frame
Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).
Title
Incidence of Severe Allergic Reactions (e.g. Anaphylaxis)
Time Frame
Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).
Title
Other Investigational Product (IP) - Related Adverse Events
Time Frame
Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).
Title
Clinically Significant Changes in Vital Signs - Body Temperature
Description
Changes in body temperature were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Time Frame
Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.
Title
Clinically Significant Changes in Vital Signs - Systolic and Diastolic Blood Pressure (BP)
Description
Changes in systolic and diastolic blood pressure (mmHg) were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Time Frame
Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.
Title
Clinically Significant Changes in Vital Signs - Respiratory Rate
Description
Changes in Respiratory rate were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Time Frame
Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.
Title
Clinically Significant Changes in Vital Signs - Pulse Rate
Description
Changes in the pulse rate (beats/minute) were assessed 15 minutes after the PK/IR infusion and compared to the pre-infusion values.
Time Frame
Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.
Title
Clinically Significant Changes in Routine Laboratory Parameters- Hematology and Chemistry
Description
Changes in clinical chemistry and hematology parameters from a normal or abnormal not clinically significant (ncs) result at screening to an abnormal and clinically significant (cs) result at the end of study assessment (EOS) are listed. Changes did occur in the following laboratory parameters: Alanine Aminotransferase (ALT) (U/L), Hemoglobin (g/L), Hematocrit, Erythrocytes(TI/L), Eosinophils/Leucocytes.
Time Frame
Throughout the entire study period from screening to completion/termination (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy).
Participant and/or legal representative has/have provided signed informed consent.
Participant has severe hemophilia A (Factor VIII (FVIII) level <1%) as confirmed by the central lab at screening or a documented FVIII activity level <1%.
Participant was previously treated with FVIII concentrates with ≥150 documented exposure days (EDs).
Participant is currently receiving prophylaxis or on-demand therapy with FVIII concentrate.
Participant has a Karnofsky performance score of ≥60 at screening.
Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥200 cells/mm^3, as confirmed by central laboratory at screening.
Participant is Hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis as assessed by the investigator.
Participant is willing and able to comply with the requirements of the study protocol.
Exclusion Criteria:
Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Unit (BU) using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay).
History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
Participant has a platelet count <100 x 10^9/L, as confirmed by central laboratory at screening.
Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
Participant has severe chronic hepatic dysfunction (eg ≥5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by the central laboratory at screening, or a documented International Normalized Ratio (INR) > 1.5).
Participant has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG.
Participant is currently using or has recently (< 30 days) used pegylated drugs (other than BAX 855) prior to study participation or is scheduled to use such drugs during trial participation.
Participant is currently participating in another clinical drug (other than BAX 855) or device study or use of another investigational product or device within 30 days prior to study entry.
Participant has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A.
Participant is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (eg, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy.
Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Bleeding and Clotting Disorders Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61614
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Children's Mercy Hospitals & Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
University of Utah Health Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
SHAT of Oncohaematology Diseases
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
MHAT 'Sv. Marina', EAD
City
Varna
ZIP/Postal Code
9003
Country
Bulgaria
Facility Name
Vilnius University Hospital Santariskiu Clinics, Public Institution
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
FSHI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"
City
Kirov
ZIP/Postal Code
610000
Country
Russian Federation
Facility Name
Hospital Universitari Son Espases
City
Palma de Mallorca
State/Province
Baleares
ZIP/Postal Code
07010
Country
Spain
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
La Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
State/Province
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Universitaetsspital Zuerich
City
Zuerich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
SI Institute of Blood Pathology and Transfusion Medicine of AMSU
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
Facility Name
Royal Free Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Children
City
London
State/Province
Greater London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
27328112
Citation
Brand B, Gruppo R, Wynn TT, Griskevicius L, Lopez Fernandez MF, Chapman M, Dvorak T, Pavlova BG, Abbuehl BE. Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients. Haemophilia. 2016 Jul;22(4):e251-8. doi: 10.1111/hae.12963. Epub 2016 Jun 21.
Results Reference
result
Learn more about this trial
Phase 3 Efficacy and Safety Study of BAX 855 in Severe Hemophilia A Patients Undergoing Surgical Procedures
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