A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects With Congenital Hemophilia A With Factor VIII Inhibitors Undergoing Surgical or Other Invasive Procedures
Phase: PHASE3
Conditions: Hemophilia A
Sponsor: Baxalta now part of Shire

CLINICAL STUDY PROTOCOL 
 
 
NCT Number:   
NCT02895945 
 
Study Title:  
A Phase 3, Multicenter, Single-arm, Open-label Study of the Efficacy and Safety 
of B-Domain Deleted Recombinant Porcine Factor VIII (BAX802) in Subjects with 
Congenital Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or Other 
Invasive Procedures 
 
 
Study Number:  
241502 
 
 
Protocol Version and Date:  
 
Original: 
 
30 Sep 2025 
Amendment 1:  
03 Feb 2016 
Amendment 4:  
28 Jun 2017 
Amendment 6:  
14 Dec 2017 
 
Note: Local protocol amendments are not included. 

BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
CLINICAL STUDY PROTOCOL
PRODUCT: BAX802
STUDY TITLE:
A Phase 3, Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of 
B-Domain Deleted Recombinant Porcine Factor VIII (BAX802) in Subjects with
Congenital Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or Other 
Invasive Procedures
STUDY SHORT TITLE: BAX802 in Congenital Hemophilia A with Inhibitors
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
ORIGINAL: 2015 SEP 30
OTHER ID(s)
NCT Number:
to be determined
EudraCT Number:
to be determined
IND NUMBER: to
be determined
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362, 
UNITED STATES
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna,
AUSTRIA
For non-commercial use only

BAX802
Page 2 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
, Clinical Development
Baxalta US Inc.
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with 
the study (eg, investigator(s), sponsor’s medical expert and study monitor, sponsor’s 
representative(s), laboratories, steering committees, and oversight committees (including 
ethics committees [ECs], as applicable) will be maintained by the sponsor and provided 
to the investigator.
For non-commercial use only

BAX802
Page 3 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. SERIOUS ADVERSE EVENT REPORTING
The investigator will comply with applicable laws/requirements for reporting serious 
adverse events (SAEs) to the ECs.
ALL SAEs ARE TO BE REPORTED ON THE ADVERSE EVENT 
ELECTRONIC CASE REPORT FORM (eCRF) WITHIN 24 HOURS AFTER 
BECOMING AWARE OF THE EVENT. IF THE eCRF IS NOT AVAILABLE 
THEN THE SAE MUST BE REPORTED ON THE SERIOUS ADVERSE 
EVENT REPORT (SAER) FORM AND TRANSMITTED TO THE SPONSOR
TO MEET THE 24 HOUR TIMELINE REQIREMENT.
See SAE Protocol Sections for further information and SAER form for 
contact information.
Further details are also available in the study team roster.
For definitions and information on the assessment of these events, refer to the following:
1. AE, Section 12.1
2. SAE, Section 12.1.1.1
3. Assessment of AEs, Section 12.1.2
For non-commercial use only

BAX802
Page 4 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
3. SYNOPSIS 
INVESTIGATIONAL PRODUCT
Name of Investigational Product (IP)
BAX802
Name(s) of Active Ingredient(s)
Recombinant Porcine Factor VIII
CLINICAL CONDITION(S)/INDICATION(S)
a
Congenital hemophilia A (CHA) patients with inhibitors to FVIII undergoing surgical and other 
invasive procedures
PROTOCOL ID
241502
PROTOCOL TITLE
A Phase 3, Multicenter, Open-label Study of the Efficacy and 
Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX802) in Subjects with Congenital Hemophilia A with Factor 
VIII Inhibitors Undergoing Surgical or Other Invasive Procedures 
Short Title
BAX802 in CHA with Inhibitors 
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2016, FEB
Primary Completion
2017, DEC 
Study Completion
2017, DEC 
Duration
20 months
STUDY OBJECTIVES AND PURPOSE
Study Purpose
To evaluate the efficacy and safety of BAX802 in males with CHA with inhibitors who are undergoing 
major or minor elective surgical, dental, or other invasive procedures.
Primary Objective
To evaluate the perioperative hemostatic efficacy of BAX802 in male subjects with CHA with inhibitors 
to human factor VIII (hFVIII) undergoing major or minor elective surgical, dental, or other invasive 
procedures as determined by the Global Hemostatic Efficacy Assessment (GHEA) score.
Secondary Objective(s)
1. To determine the safety of BAX802 used in the perioperative setting by assessing:

The development of and change in titer of anti-pFVIII and anti-hFVIII inhibitory antibodies 
(binding and/or neutralizing), and development of binding antibodies to baby hamster kidney 
(BHK) proteins

The occurrence of thrombotic events and/or allergic reactions to BAX802

The occurrence of adverse events (AEs) related to BAX802

The occurrence of clinically significant changes in vital signs and routine laboratory parameters 
related to BAX802
For non-commercial use only

BAX802
Page 5 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. To determine the intra- and postoperative blood loss at the end of surgery, compared to the estimated 
volume of expected average and maximum blood loss in a comparable healthy individual as 
predicted preoperatively by the investigator/surgeon
3. To determine the daily and total weight-adjusted administration of BAX802 per subject
4. To determine the blood product utilization 
5. To determine the occurrence of bleeding episodes during the intra- and postoperative periods and 
additional need for surgical intervention
6. To evaluate any intercurrent, unrelated bleeding episodes in the postoperative period.
STUDY DESIGN
Study Type/ Classification/ 
Discipline
Efficacy and Safety
Control Type
No control
Study Indication Type
Treatment
Intervention model
single-group
Blinding/Masking
Open-label
Study Design
This study is a Phase 3, prospective, open-label, uncontrolled, 
multicenter study to evaluate the efficacy and safety of BAX802 in at least 
10 evaluable male subjects with CHA with inhibitors to hFVIII who are 
undergoing major and minor surgical, dental or other invasive procedures. 
At least 5 of the procedures must be major surgeries in 5 evaluable 
subjects.
Planned Duration of 
Subject Participation
The duration of subject participation depends on the nature of the invasive 
procedure: it will run from the signing of the informed consent until 
completion of the End of Study Visit (at least 6 weeks post-surgery 
[Day 0]).
Primary Outcome Measure 
The primary outcome measure is the GHEA score, which is composed of 3 individual ratings:

Assessment of intraoperative hemostatic efficacy of BAX802 performed by the operating surgeon 

Assessment of postoperative hemostatic efficacy of BAX802 at postoperative Day 1 (approximately 
24 hours after surgery) performed by the operating surgeon

Assessment of postoperative hemostatic efficacy of BAX802 at Day 14, performed by the 
investigator. 
The scores of each of the 3 individual ratings described above, will be added together to form a GHEA 
score 
For non-commercial use only

BAX802
Page 6 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Secondary Outcome Measure(s)
Efficacy 
1. Intra- and postoperative blood loss compared to the estimated volume of expected average blood loss 
and expected maximum blood loss in a comparable healthy individual as predicted preoperatively by 
the investigator/surgeon at the following time points:

Intraoperative, at the end of surgery

Postoperative Day 1, approximately 24 hours after surgery

Postoperative Day 14 
2. Daily and total weight-adjusted administration of BAX802 per subject
3. Volume of blood, red blood cells, platelets, and other blood products transfused
4. Occurrence of bleeding episodes during the intra- and postoperative periods and additional need for 
surgical intervention
5. Efficacy of the treatment of intercurrent, unrelated bleeding episodes in the postoperative period. 
Safety
1. Development of, and changes to, the titer of inhibitory and binding antibodies to recombinant porcine 
factor VIII (rpFVIII)
2. Development of, and changes to, the titer of inhibitory and binding antibodies to hFVIII
3. Development of binding antibodies to BHK proteins
4. Occurrence of thrombotic events
5. Incidence of severe allergic reactions (eg, anaphylaxis)
6. Incidence of other IP-related AEs
7. Incidence of clinically significant changes in vital signs and routine laboratory parameters 
(hematology, clinical chemistry)
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Active Product
Dosage form: Injectable Reconstituted Solution
Dosage frequency: PRN = as needed
Mode of Administration: intravenous bolus
SUBJECT SELECTION
Targeted Accrual
Enroll 10 evaluable subjects
Number of 
Groups/Arms/Cohorts
1 arm: 10 evaluable adult male subjects (≥ 18 to ≤ 65 years old) with CHA 
with inhibitors to FVIII undergoing surgical and other invasive procedures 
for efficacy and safety evaluation
For non-commercial use only

BAX802
Page 7 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Inclusion Criteria
1. Subject is ≥ 18 to ≤ 65 years old at the time of screening
2. Subject has provided signed informed consent
3. Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤ 2%) CHA with inhibitors 
to human FVIII, as tested at screening at the central laboratory
4. Subject requires elective surgery or other invasive procedures
5. Subject is not currently receiving ITI therapy
6. Subject has a Karnofsky performance score of ≥ 60
7. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and 
CD4+ count ≥ 200 cells/mm3 at screening
8. Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; 
or HCV+ with chronic stable hepatitis disease
9. Subject is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
1. The subject requires emergency surgery
2. The subject’s weight is < 35 kg or > 120 kg
3. Clinically symptomatic liver disease (eg, ≥ 5 X upper limit of normal alanine aminotransferase 
[ALT], as confirmed by central laboratory at screening, clinical evidence of portal hypertension, 
severe hypoalbuminemia or a documented prothrombin time/international normalized ratio [PT/INR] 
> 1.5)
4. Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as confirmed by central 
laboratory at screening
5. Anti-porcine inhibitor > 10 Bethesda units (BU) prior to surgery
6. Platelet count < 100,000/µl
7. Active condition of coagulation disorder such as von Willebrand disease
8. Planned use of α-interferon with or without ribavarin 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
9. Known hypersensitivity to rpFVIII, or hamster or murine proteins
10. Subject has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in 
another clinical study involving an IP or investigational device during the course of this study
11. Unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the investigator 
For non-commercial use only

BAX802
Page 8 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
STATISTICAL ANALYSIS
Sample Size Calculation
The sample size of 10 evaluable male subjects, 5 of which must have major surgery as defined in the 
protocol, was chosen to provide sufficient evidence of safety and effectiveness for this indication and is not 
based on statistical considerations. 
Planned Statistical Analysis
Datasets and Analysis Cohorts
The safety analysis set (SAS) will be comprised of all subjects who received any amount of BAX802. The 
full analysis set (FAS) will comprised of all subjects with at least one available hemostatic assessment. The 
per-protocol analysis set (PP) will comprise all subjects with available perioperative hemostatic efficacy 
assessed by:
i)
the operating surgeon within 60 minutes post-surgery
ii)
postoperative hemostatic control assessed by the operating surgeon postoperatively at 24 hours, and
iii)
postoperative hemostatic control assessed by the investigator during Day 14. 
Only subjects who meet all study entry criteria and who have no major protocol violations that might 
impact hemostatic efficacy assessments will be included in the PP analysis set.
Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy assessed 
intraoperatively by the surgeon and postoperatively by the investigator (hemophilia physician) at 
postoperative Day 1 (ie, the day following the day of surgery) and at postoperative Day 14 visit, and will be 
summarized by the GHEA score and rated “excellent”, “good”, “moderate” and “none”.
A treatment success will be defined as a rating of excellent and/or good. 
Point estimates and corresponding two-sided exact confidence intervals (CIs) at the 90% confidence level 
will be calculated for the rate of hemostatic efficacy assessments with excellent/good outcome.
The primary efficacy analysis will be based on the FAS. As a supportive analysis, the same calculations 
will also be carried out on the PP population.
Secondary Outcome Measures
Secondary hemostatic efficacy analysis:
Descriptive statistics will be used to summarize the actual blood loss and transfusion requirements. The 
summary of average daily and total weight-adjusted doses (average through postoperative Day 14) of 
BAX802 per subject as well as the occurrence of bleeding episodes will be provided using descriptive 
statistics. For intercurrent, unrelated bleeding episodes in the postoperative period, descriptive statistics will 
be used to summarize the overall hemostatic efficacy rating at 24 ±2 hours after initiation of treatment and 
at resolution of bleed. The secondary efficacy analysis will be performed on the FAS only.
For non-commercial use only

BAX802
Page 9 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will 
be summarized by presenting the number and percentage of subjects having any AE, having an AE in each 
system organ class, and having each individual AE as reported by preferred term. In the summaries, AEs 
will be counted only once per patient. If a patient reports the same AE more than once, it will be counted 
with its worst severity and closest relationship to the study product.
The number of subjects who experienced serious adverse events (SAEs) and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the number of IP 
related AEs will be tabulated and subcategorized for thrombotic events, inhibitory and total binding 
antibodies to rpFVIII and hFVIII, and binding antibodies to BHK proteins.
An overview table for AEs will be provided, presenting the number of AEs, the number of subjects with 
AEs and the corresponding percent of subjects in total, and by seriousness and relationship to study 
treatment. An additional summary table will present the total number of (mild, moderate, severe) AEs by 
system organ class and preferred term with relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. Descriptive 
statistics of changes from baseline (Day 0 - prior to surgery) by study visits will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. Furthermore, laboratory 
abnormalities will be analyzed by shift tables where each subject will be counted only once with the worst 
grade in the summary tables.
Vital signs assessments as well as the corresponding changes from baseline will be summarized 
descriptively at each scheduled assessment.
For non-commercial use only

BAX802
Page 10 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
4. TABLE OF CONTENTS
1. STUDY PERSONNEL ................................................................................................. 2
1.1 Authorized Representative (Signatory) / Responsible Party .............................. 2
1.2 Study Organization................................................................................................. 2
2. SERIOUS ADVERSE EVENT REPORTING........................................................... 3
3. SYNOPSIS..................................................................................................................... 4
4. TABLE OF CONTENTS ........................................................................................... 10
5. LIST OF ABBREVIATIONS .................................................................................... 15
6. BACKGROUND INFORMATION .......................................................................... 17
6.1 Description of Investigational Product ............................................................... 17
6.2 Clinical Condition/Indication .............................................................................. 17
6.3 Population To Be Studied..................................................................................... 19
6.4 Findings from Nonclinical and Clinical Studies................................................. 19
6.4.1 Finding from Nonclinical Studies................................................................. 19
6.4.2 Finding from Clinical Studies....................................................................... 20
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 23
6.6 Compliance Statement.......................................................................................... 24
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 25
7.1 Study Purpose ....................................................................................................... 25
7.2 Primary Objective................................................................................................. 25
7.3 Secondary Objectives ........................................................................................... 25
8. STUDY DESIGN......................................................................................................... 26
8.1 Brief Summary...................................................................................................... 26
8.2 Overall Study Design............................................................................................ 26
8.2.1 Types of Interventions................................................................................... 26
8.2.1.1 Major Surgeries ...................................................................................... 27
8.2.1.2 Minor Surgeries ...................................................................................... 27
8.2.2 Dose Selection Rationale ............................................................................... 28
8.3 Duration of Study Period(s) and Subject Participation .................................... 30
8.4 Outcome Measures ............................................................................................... 30
8.4.1 Primary Outcome Measure .......................................................................... 30
8.4.2 Secondary Outcome Measures ..................................................................... 32
For non-commercial use only

BAX802
Page 11 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2.1 Efficacy .................................................................................................... 32
8.4.2.2 Safety........................................................................................................ 33
8.5 Randomization and Blinding............................................................................... 33
8.6 Study Stopping Rules............................................................................................ 33
8.7 Investigational Product(s).................................................................................... 33
8.7.1 Packaging, Labeling, and Storage................................................................ 34
8.7.2 Reconstitution and Administration.............................................................. 34
8.7.3 Description of Treatment.............................................................................. 35
8.7.3.1 FVIII Maintenance Plan ........................................................................ 35
8.7.3.2 Perioperative Dosing .............................................................................. 35
8.7.3.3 Dosing Schedule and Requirements...................................................... 35
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics .................................... 39
8.7.5 Investigational Product Accountability ....................................................... 40
8.8 Source Data ........................................................................................................... 40
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 41
9.1 Inclusion Criteria.................................................................................................. 41
9.2 Exclusion Criteria................................................................................................. 41
9.3 Withdrawal and Discontinuation ........................................................................ 42
10. STUDY PROCEDURES .......................................................................................... 43
10.1 Informed Consent and Enrollment ................................................................... 43
10.2 Subject Identification Code................................................................................ 43
10.3 Screening and Study Visits................................................................................. 43
10.4 Study Periods....................................................................................................... 44
10.4.1 Discharge/End of Study Visit...................................................................... 44
10.4.2 Unscheduled Visits for Unrelated Bleeding Episodes............................... 44
10.5 Medications and Non-Drug Therapies.............................................................. 45
10.6 Rescue Medications............................................................................................. 46
10.7 Subject Completion/Discontinuation ................................................................ 46
10.8 Procedures for Monitoring Subject Compliance............................................. 47
11. ASSESSMENT OF EFFICACY.............................................................................. 48
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score 48
11.2 Secondary Efficacy Endpoints........................................................................... 48
11.2.1 Blood Loss..................................................................................................... 48
11.2.2 Blood Transfusions ...................................................................................... 48
11.2.3 Bleeding Episodes ........................................................................................ 49
11.2.4 BAX802 Administration.............................................................................. 49
11.2.5 Hemostatic Efficacy Rating for Treatment of Inter-current, Unrelated 
Bleeding Episodes.......................................................................................... 49
11.3 Factor VIII Activity............................................................................................ 50
11.3.1 Blood Sampling and Processing for FVIII Analysis................................. 51
For non-commercial use only

BAX802
Page 12 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY................................................................................... 52
12.1 Adverse Events.................................................................................................... 52
12.1.1 Definitions..................................................................................................... 52
12.1.1.1 Serious Adverse Event.......................................................................... 52
12.1.1.2 Non-Serious Adverse Event ................................................................. 53
12.1.1.3 Unexpected Adverse Events................................................................. 53
12.1.1.4 Preexisting Diseases.............................................................................. 53
12.1.2 Assessment of Adverse Events.................................................................... 53
12.1.2.1 Severity .................................................................................................. 54
12.1.2.2 Causality................................................................................................ 55
12.1.2.3 Safety Reporting ................................................................................... 56
12.2 Urgent Safety Measures ..................................................................................... 57
12.3 Untoward Medical Occurrences........................................................................ 58
12.4 Non-Medical Complaints ................................................................................... 58
12.5 Medical, Medication, and Non-Drug Therapy History................................... 59
12.6 Physical Examinations........................................................................................ 59
12.7 Clinical Laboratory Parameters........................................................................ 59
12.7.1 Hematology, Clinical Chemistry, and Urinalysis...................................... 60
12.7.2 Viral Serology............................................................................................... 60
12.7.3 Immunogenicity ........................................................................................... 61
12.7.4 Assessment of Laboratory Values .............................................................. 61
12.7.4.1 Assessment of Abnormal Laboratory Values..................................... 61
12.7.5 Biobanking.................................................................................................... 62
12.8 Vital Signs............................................................................................................ 62
12.9 Karnofsky Performance Test............................................................................. 63
12.10 Special Treatment Considerations .................................................................. 63
13. STATISTICS............................................................................................................. 64
13.1 Sample Size and Power Calculations ................................................................ 64
13.2 Datasets and Analysis Cohorts .......................................................................... 64
13.2.1 Safety Analysis Set....................................................................................... 64
13.2.2 Efficacy Datasets.......................................................................................... 64
13.2.2.1 Full Analysis Set.................................................................................... 64
13.2.2.2 Per-Protocol Analysis Set..................................................................... 64
13.3 Handling of Missing, Unused, and Spurious Data........................................... 65
13.4 Methods of Analysis............................................................................................ 65
13.4.1 Primary Outcome Measure......................................................................... 65
13.4.2 Secondary Outcome Measures ................................................................... 65
13.4.2.1 Secondary Hemostatic Efficacy Analysis ........................................... 65
13.4.2.2 Safety Analysis ...................................................................................... 66
13.5 Planned Interim Analysis of the Study ............................................................. 67
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 67
For non-commercial use only

BAX802
Page 13 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 68
15.1 Investigator’s Responsibility.............................................................................. 68
15.1.1 Investigator Report and Final Clinical Study Report.............................. 68
15.2 Training ............................................................................................................... 68
15.3 Monitoring........................................................................................................... 68
15.4 Auditing ............................................................................................................... 68
15.5 Non-Compliance with the Protocol ................................................................... 69
15.6 Laboratory and Reader Standardization ......................................................... 69
16. ETHICS ..................................................................................................................... 70
16.1 Subject Privacy ................................................................................................... 70
16.2 Ethics Committee and Regulatory Authorities................................................ 70
16.3 Informed Consent ............................................................................................... 70
16.4 Internal Safety Monitoring Committee ............................................................ 71
17. DATA HANDLING AND RECORD KEEPING................................................... 72
17.1 Confidentiality Policy ......................................................................................... 72
17.2 Study Documentation and Case Report Forms ............................................... 72
17.3 Document and Data Retention........................................................................... 72
18. FINANCING AND INSURANCE........................................................................... 73
19. PUBLICATION POLICY........................................................................................ 73
20. SUPPLEMENTS....................................................................................................... 74
20.1 Procedures per Study Period............................................................................. 74
20.2 Study Flow Chart................................................................................................ 79
20.3 Schedule of Study Procedures and Assessments.............................................. 80
20.4 Clinical Laboratory Assessments ...................................................................... 82
20.5 Schedule of Study Procedures and Clinical Laboratory Assessments for 
Unrelated Bleeding Episodes in the Postoperative Period................................ 84
20.6 Global Efficacy Assessments Scores.................................................................. 85
20.7 Definitions............................................................................................................ 86
20.7.1 Joint Bleeds................................................................................................... 86
20.7.2 Muscle Bleeds............................................................................................... 86
21. REFERENCES.......................................................................................................... 87
INVESTIGATOR ACKNOWLEDGEMENT.............................................................. 91
For non-commercial use only

BAX802
Page 14 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Tables
Table 1: Global Hemostatic Efficacy Assessment (GHEA)............................................. 31
Table 2: Intraoperative Efficacy Assessment Scale.......................................................... 31
Table 3: Postoperative Efficacy Assessment Scale (Postoperative Day 1) ...................... 31
Table 4: Postoperative Efficacy Assessment Scale (Day 14) ........................................... 32
Table 5: Dosing for Perioperative Management............................................................... 36
Table 6: BAX802 Treatment Guidelines for Unrelated Bleeding Episodes..................... 39
Table 7: Efficacy Rating Scale for Treatment of Bleeding Episodes ............................... 50
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502 ...... 74
Table 9: Schedule of Study Procedures and Assessments................................................ 80
Table 10: Clinical Laboratory Assessments ..................................................................... 82
Table 11: Schedule of Study Procedures and Assessments for Unrelated Bleeding 
Episodes.................................................................................................................... 84
Table 12: Combinations of Individual Efficacy Assessments (A, B, C) and GHEA Score
................................................................................................................................... 85
Figures
Figure 1 Visit Schedule..................................................................................................... 79
For non-commercial use only

BAX802
Page 15 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
5. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
AICC
anti-inhibitor coagulant complex 
ALT
alanine aminotransferase
aPCC
activated prothrombin complex concentrate 
B19V
parvovirus B19
BHK
baby hamster kidney 
BU
Bethesda units
CI
confidence interval
CHA
Congenital Hemophilia A
CRF
case report form
CRO
Contract Research Organization 
EC
ethics committee
EBL
estimated blood loss
eCRF
electronic case report form
EDC
electronic data capture
FAS
full analysis Set 
GCP
Good Clinical Practice
GHEA
Global Hemostatic Efficacy Assessment 
HAV
hepatitis A virus
HBV
hepatitis B virus
Hct
hematocrit
HCV
hepatitis C virus
HEV
hepatitis E virus
hFVIII
human factor VIII 
HIV
human immunodeficiency virus
IB
Investigator’s brochure
ICF
informed consent form 
ICH
International Conference on Harmonisation
IP
investigational product
IPC
intermittent pneumatic compression 
iSMC
internal Safety Monitoring Committee 
ITI
immune tolerance induction
For non-commercial use only

BAX802
Page 16 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Abbreviation
Definition
LMWH
low molecular weight heparin 
MedDRA
Medical Dictionary for Regulatory Activities 
NMC
Non-medical complaint
OR
operating room
PCR
polymerase chain reaction 
pFVIII
porcine factor VIII 
PP
Per Protocol (analysis set)
PRN
“pro re nata” (as needed)
PT/INR
prothrombin time/international normalized ratio 
PV
plasma volume
rhFVIII
recombinant human factor VIII 
rpFVIII
recombinant porcine factor VIII 
SAE
serious adverse event
SAER
serious adverse event report
SAP
statistical analysis plan 
SAS
safety analysis set 
SIC
subject identification code
TGA
thrombin generation assays 
VIIa
activated factor VII 
WFH
World Federation of Hemophilia
For non-commercial use only

BAX802
Page 17 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
The investigational product (IP), BAX802, is a recombinant form of porcine factor VIII 
(rpFVIII) from which the B domain has been deleted. Deletion of the B domain does not 
affect the safety or efficacy of this recombinant form of human factor VIII (rhFVIII) in 
the treatment of hemophilia A. BAX802 (rpFVIII) is being developed for the 
perioperative management of hemostasis in subjects with congenital hemophilia A 
(CHA) with inhibitors to human factor VIII (hFVIII) undergoing surgical or other 
invasive procedures. This rpFVIII was approved by the United States Food and Drug 
Administration (FDA) in 2014 for the treatment of bleeding episodes in adults with 
acquired hemophilia A (AHA; non hemophilia subjects developing spontaneous 
autoantibody inhibitors to hFVIII) under the trade name OBIZUR®.
6.2 Clinical Condition/Indication 
Congenital hemophilia A is a congenital bleeding disorder caused by a deficiency or 
complete absence of coagulation factor VIII (FVIII) 1 and is referred to as CHA in order 
to differentiate it from AHA, which is a rare autoimmune disease with different bleeding 
patterns caused by immunoglobulin G antibodies that bind to specific domains on the 
FVIII molecule, in a person with a negative personal or family history of a 
coagulopathy.2
Overall, CHA accounts for about 80% of hemophiliacs. It affects all ethnic populations 
and its prevalence varies among different countries, but is estimated at a rate of 3 to 
20 cases per 100,000 population. The World Federation of Hemophilia (WFH) has 
estimated the total number of hemophilia cases at about 500,000 universally, of which 
one-third are diagnosed. The tendency to bleed in these subjects correlates with the 
plasma level of FVIII. This lifelong disorder has three clinical phenotypes (severe, 
moderate, and mild) that correlate with FVIII levels in plasma (< 1%, 1 - 5%, and 
5 - 30%, respectively).3
Subjects with hemophilia A typically develop recurrent bleeding episodes. The most 
effective approach for treatment of acute bleeding episodes in subjects with hemophilia A 
is hFVIII replacement therapy.4,5  However, a major complication in the treatment of 
subjects with A is the development of neutralizing antibodies (inhibitors) to hFVIII, 
which impair the efficacy of replacement therapy with hFVIII concentrates. Inhibitor 
development occurs more frequently among patients with severe or moderately severe 
hemophilia, and approximately 30% of patients with severe CHA develop inhibitors. 
For non-commercial use only

BAX802
Page 18 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
In CHA patients with high-responding inhibitors, standard replacement therapy with 
FVIII concentrates is usually ineffective, resulting in poor control of hemorrhagic 
episodes. This in turn increases the risk of morbidity, mortality, orthopedic complications 
and disability, as well as reduced quality of life, compared with patients without 
inhibitors.6 Patients with CHA with inhibitors are also at risk of perioperative bleeding 
complications, since replacement of the missing coagulation factor is ineffective, 
presenting a therapeutic challenge in elective or emergency surgery.7
Currently Available Treatments and Unmet Medical Need
In CHA patients with transient, low-responding and/or low-titers (< 5 Bethesda units 
[BU]/mL) inhibitors, increased doses of FVIII may be sufficient to overcome the 
inhibitor and provide hemostasis. In CHA patients with high-responding inhibitors 
(> 5 BU/mL), standard replacement therapy with FVIII concentrates is usually 
ineffective, resulting in poor control of hemorrhagic episodes. 
Alternative therapies are required for subjects with inhibitors who no longer respond to 
hFVIII replacement therapy. Recombinant activated factor VII (rFVIIa, NovoSeven®) 
and FEIBA (Factor VIII inhibitor bypassing activity; anti-inhibitor coagulant complex 
[AICC]) bypass the normal coagulation cascade and hence the FVIII inhibitors, and are 
therefore referred to as bypassing agents. Although these agents are able to manage 
bleeding in the presence of inhibitors, they do not attempt to restore the normal pathways 
of hemostasis, but instead boost thrombin generation despite a lack of platelet-surface 
FVIIIa–FIXa (‘tenase’) activity.6  The measurement of levels of factor VIIa in the 
subject’s plasma cannot be used as a clinically relevant surrogate marker and does not 
correlate with clinical outcome. Without an adequate biomarker, the dosage and 
treatment schedule cannot be clearly defined.8 In addition, the response to rFVIIa 
treatment may be inconsistent both from subject to subject and between different bleeds 
in the same subject. Because FEIBA is a human plasma fraction containing several 
coagulation factors, it has the potential to transmit human pathogens and may also cause 
thromboembolic events. Since the plasma fraction also contains hFVIII, it has been 
associated with a rise in hFVIII antibodies in approximately 20% of subjects.9  
Moreover, as with rFVIIa, there is no validated biomarker that correlates with the clinical 
outcome with FEIBA treatment, although both thrombin generation assays (TGA) and 
whole blood viscoelastic assays have been evaluated for this purpose with some 
success.10
For non-commercial use only

BAX802
Page 19 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The ultimate goal of treatment for these patients is eradication of the inhibitor through 
immune tolerance induction (ITI), which involves frequent and long-term administration 
of factor concentrates in an attempt to build tolerance in the immune system to FVIII or 
factor IX, and thus restore responsiveness to factor replacement therapy. However, 
ITI fails in approximately 30% of inhibitor patients with CHA.6
There is therefore a clinical need for an effective hemostatic agent for use in subjects 
with CHA who have inhibitors to hFVIII, and which allows monitoring of hemostatic 
efficacy based upon measurement of plasma FVIII activity levels, thus facilitating early 
determination of clinical benefit and the patient’s clinical status.
6.3 Population To Be Studied
The study population will comprise 10 male subjects with CHA with inhibitors to hFVIII 
undergoing major or minor elective surgical, dental, or other invasive procedures. Adult 
(≥ 18 and ≤ 65 years) male subjects will be considered to be eligible provided that they 
satisfy all of the inclusion criteria listed in Section 9.1 and none of the exclusion criteria 
listed in Section 9.2.
6.4 Findings from Nonclinical and Clinical Studies
6.4.1 Finding from Nonclinical Studies
Nonclinical studies were performed with rpFVIII to demonstrate hemostatic activity in 
two animal models of hemophilia A (mice and dogs), local and systemic tolerance in a 
range of doses in single or repeat dose toxicology studies in monkeys, pharmacokinetics 
(PK) in dogs and monkeys, and immunogenicity in mice and monkeys.
Compatibility with the usual injection materials (needles, plastic syringes, and butterfly 
infusion needles with tubing) has been demonstrated. Studies in monkeys demonstrated 
the tolerability of repeated single daily injections of rpFVIII at doses up to 1000 U/kg, 
with injections at each dose level given once daily for 7 days. In two animal models of 
hemophilia A (mice and dogs), the hemostatic activity of rpFVIII was studied in 
comparison with Hyate:C. The rpFVIII was found to be efficacious in a dose-related 
fashion in controlling the bleeding associated with a standardized hemorrhagic insult. No 
animal studied was observed to have had an acute reaction to the injection of rpFVIII.
For non-commercial use only

BAX802
Page 20 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.4.2 Finding from Clinical Studies
The safety and efficacy of rpFVIII was explored in four clinical trials prior to marketing 
approval:
OBI-1-101: a Phase I, multicenter, randomized, double-blinded, double-dummy, 
parallel-group, comparison of the safety, tolerance, and PK study of rpFVIII versus 
Hyate:C was conducted.11
OBI-1-201: a Phase II, prospective, open-label, non-comparative study was 
conducted to assess the hemostatic activity of rpFVIII. Eligible subjects had a 
clinical diagnosis of hemophilia A with inhibitors to hFVIII, an anti-pFVIII
inhibitor antibody titer < 20 BU at screening, and an uncomplicated joint or soft 
tissue bleed, or other non-life threatening and non-limb threatening bleeding 
episode.12
OBI-1-301: a multicenter, open-label, single-cohort, prospective, Phase II/III study 
of rpFVIII in subjects with acquired hemophilia to determine the hemostatic 
efficacy and safety of rpFVIII in the control of serious bleeding episodes.13
OBI-1-302: a prospective, non-randomized, open-label study designed to assess 
treatment of serious bleeding episodes with rpFVIII in subjects with CHA who had 
developed anti-hFVIII inhibitors; this study was terminated by the sponsor after one 
subject was treated for administrative reasons, not due to safety or lack of efficacy 
concerns.
In all clinical studies, rpFVIII was generally well tolerated. There were no drug-related 
AEs reported in subjects who received rpFVIII in the Phase I study. One subject in the 
Phase II study (OBI-1-201) experienced pruritus (that resolved with diphenhydramine) 
that was possibly related to study drug. This AE occurred during the first bleeding 
episode, but the subject did not have a reaction during a second rpFVIII treated bleeding 
episode. In the Phase I and Phase II studies, no AEs led to treatment interruption, 
discontinuation from the study, or death. Vital signs, laboratory values, medical history 
and physical examination findings were within normal parameters for both studies and 
raised no safety concerns. 
In the Phase II study (OBI-1-201), the ITT Population consisted of nine male subjects 
with CHA and with an inhibitor antibody to hFVIII. Six of the subjects (67%) were 
black and 3 subjects (33%) were Caucasian. The mean age of the subject population 
was 23.7 years (Range: 14 to 34). The primary efficacy objective of the study was 
to evaluate the hemostatic efficacy of rpFVIII in the treatment of non-life/non-limb 
threatening bleeds in subjects with CHA and inhibitors.
For non-commercial use only

BAX802
Page 21 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
A total of 25 bleeds in 9 subjects were treated with rpFVIII and all bleeds were 
successfully controlled with 8 or less injections of rpFVIII. The median number of 
rpFVIII injections administered per bleeding episode was 1.0 (Range: 1 to 8) and the 
median time from bleeding onset to treatment was 5.67 hours (range: 1.5 to 20.0 hours). 
Across all bleeding episodes the median total dose of rpFVIII per bleeding episode was 
224.1 U/kg (range: 50.0 to 1066.4 U/kg). The median initial Treatment Dose (including 
the Loading Dose if applicable), was 159 U/kg (Range: 50 to 576 U/kg) and resulted in a 
median increase of FVIII plasma level of 16 % with the 1-stage clotting assay (Range: 
0.5 to 427 %) and a median increase of 17% with the chromogenic assay (Range: 0 to 
248 %). Twenty of the 25 (80%) bleeds were controlled within 6 hours having been 
administered one Treatment Dose of rpFVIII. For those 20 bleeds controlled with 
1 Treatment Dose (including the Loading Dose if applicable), the median dose was 
200.8 U/kg. rpFVIII was well tolerated and of the reported AEs (n=61) only 18 were 
considered treatment emergent. Two subjects reported an AE that was possibly related to 
study drug. One AE of itching/pruritus during the first bleeding episode but without 
reaction during a second rpFVIII treated bleeding episode. The second AE was a report 
of increased ALT and AST, possibly associated with a confirmed Hepatitis C infection, 
while it was uncertain whether the corresponding blood sample was taken before or after 
rpFVIII administration. Three subjects suffered treatment emergent SAEs but none were 
considered related to study drug. No reported AE led to treatment interruption, 
discontinuation from the study or death. Eight out of 9 (8/9, 89%) subjects developed 
anti-pFVIII antibodies following exposure to rpFVIII. In subjects that received repeated 
rpFVIII treatment, higher anti-pFVIII titers did not affect efficacy or safety and no 
increase in AEs or bleeding episodes were reported in the subjects with the highest titers. 
Regardless of the observed anti-pFVIII titers at pre-treatment or the obtained FVIII 
recovery values after treatment initiation, all bleeding episodes were successfully 
controlled. Analyses of baby hamster kidney (BHK; host cell line) antibody levels 
indicated that no subjects produced detectable levels of antibodies against BHK.
In the prospective, open-label trial (OBI-1-301), the efficacy of rpFVIII for the 
treatment of serious bleeding episodes in subjects with AHA was investigated. The 
trial was conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects 
diagnosed with AHA, having auto-immune inhibitory antibodies to hFVIII, and 
experiencing serious bleeding episodes that required hospitalization. Subjects with a 
prior history of bleeding disorders other than AHA, anti-pFVIII antibody titer > 20 BU, 
or in whom the bleeding episode was judged likely to resolve on its own, were excluded. 
One subject was considered evaluable at study entry; however, it was later determined 
that this subject did not have AHA, leaving 28 subjects evaluable for efficacy. 
For non-commercial use only

BAX802
Page 22 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Of the 28 subjects evaluable for efficacy, all subjects had a positive response to treatment 
for the initial bleeding episodes at 24 hours after dosing. A positive response was 
observed in 95% (19/20) of subjects evaluated at 8 hours and 100% (18/18) at 16 hours. 
In addition to response to treatment, the overall treatment success was determined by the 
investigator based on his/her ability to discontinue or reduce the dose and/or dosing 
frequency of rpFVIII. A total of 24/28 subjects (86%) had successful treatment of the 
initial bleeding episode. Of those subjects treated with rpFVIII as first-line therapy, 
defined as no immediate previous use of anti-hemorrhagic agents prior to the first 
rpFVIII treatment, 16/17 subjects (94%) had eventual treatment success reported. Eleven 
subjects were reported to have received anti-hemorrhagics (eg. rFVIIa, activated 
prothrombin-complex concentrate, tranexamic acid) prior to first treatment with rpFVIII. 
Of these 11 subjects, 8 had eventual successful treatment (73%). No related serious 
adverse reactions occurred. Non-serious adverse events related to treatment were noted 
and assessed by the investigator in 6/29 subjects (20.7%). One subject had mild 
tachycardia, hypotension and constipation. One subject had 2 instances of mild PICC line 
occlusion. One subject had a mild hypofibrogenemia and 1 subject had moderate mental 
status changes. All of these adverse effects completely resolved. Two subjects developed 
anti-porcine FVIII inhibitors after infusion of study drug (range 8 - 51 BU) and were 
discontinued from treatment; however both subjects had a positive response to treatment 
at the 24 hour primary endpoint assessment. An investigation was conducted by the 
sponsor and, in summary, the 2 incidences of anti-porcine FVIII inhibitors were 
considered related to rpFVIII treatment, while the other non-serious treatment-related 
adverse events were considered as unlikely to be related to rpFVIII. Anti-porcine FVIII 
inhibitors were detected prior to infusion in 10/29 patients (range 0.8 - 29 BU). All of 
these subjects had a positive response at 24 hours post-rpFVIII first infusion. No 
anti-BHK antibodies were observed in any of the 29 treated subjects.
At the time of OBIZUR® marketing approval, the clinical trial data indicated that rpFVIII 
was well tolerated and had demonstrated effectiveness in the control of bleeding in study 
subjects. No post-marketing adverse reactions had been reported per the most recent 
Company Core Data Sheet for OBIZUR® (22 July 2015).14
For non-commercial use only

BAX802
Page 23 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Porcine factor VIII (Hyate:C), derived from porcine plasma, had been used successfully 
starting in the 1980s to achieve hemostasis in the presence of anti-hFVIII inhibitors, as 
the antibodies generally have low immunological cross-reactivity with porcine factor VIII 
(pFVIII).15 However, the number of hemophilia A subjects who were appropriate 
candidates to receive Hyate:C was limited by the degree to which their anti-hFVIII 
antibodies cross-reacted with pFVIII and the presence of any anti-pFVIII inhibitors. 
While a median inhibitor cross-reactivity observed to porcine VIIIC was only 15%, an 
absent, intermediate, or brisk specific anti-porcine anamnestic response was observed in 
29%, 40%, and 31% of patients, respectively.16 The commercial production of Hyate:C 
was discontinued in 2005 due to problems with sourcing suitable porcine plasma, but not 
due to any safety or efficacy concerns. 
BAX802 is a B-domain deleted rpFVIII glycoprotein which is being developed for the 
perioperative management of hemostasis in subjects with CHA with FVIII inhibitors 
undergoing surgical or other invasive procedures. B-domain deleted rpFVIII glycoprotein 
has been extensively studied. BAX802 (as marketed OBIZUR®) is not currently indicated 
for the treatment of CHA.17
OBIZUR® was approved based on the safety and efficacy data from 28 subjects with 
AHA treated with B-domain deleted rpFVIII glycoprotein in the phase 2/3 open-label 
clinical study OBI-1-301. The safety, hemostatic activity, and PK profile of B-domain 
deleted rpFVIII glycoprotein was also supported by results of an open-label phase 2 study 
in patients with CHA with inhibitors (CSR OBI-1-201), and a randomized phase 1 study 
comparing B-domain deleted rpFVIII glycoprotein with a plasma-derived porcine 
factor VIII (CSR OBI-1-101). 
The data supported the use of B-domain deleted rpFVIII glycoprotein to treat serious 
bleeding episodes in AHA patients (Section 6.4.2). It was demonstrated that B-domain 
deleted rpFVIII glycoprotein provides benefit to AHA patients who are unresponsive to 
alternative agents with an improved dosing algorithm. It was possible to monitor 
hemostatic efficacy based upon measurement of plasma FVIII activity levels, thus 
facilitating early determination of clinical benefit and the patient’s clinical status. An 
additional benefit to the patient was that it was possible to adjust the dose based on the 
FVIII levels rather than follow fixed dosing, ensuring that adequate doses were 
administered to achieve hemostasis.
For non-commercial use only

BAX802
Page 24 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The most frequently reported adverse reaction in patients with AHA was the development 
of inhibitors to pFVIII.17
Overall, efficacy and safety clinical data for OBIZUR supported a favorable benefit/risk 
determination for the proposed indication of treatment of bleeding episodes in adults with 
AHA.
These data support the investigation of efficacy and safety of BAX802 in subjects with 
CHA with inhibitors undergoing surgical or other invasive procedures. 
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International 
Conference on Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, 
April 1996), Title 21 of the US Code of Federal Regulations (US CFR), the European 
Clinical Trial Directive (2001/20/EC and 2005/28/EC), and applicable national and local 
regulatory requirements.
For non-commercial use only

BAX802
Page 25 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to evaluate the efficacy and safety of BAX802 in males with 
CHA with inhibitors who are undergoing major or minor elective surgical, dental, or 
other invasive procedures. 
7.2 Primary Objective
The primary objective of the study is to evaluate the perioperative hemostatic efficacy of 
BAX802 in male subjects with CHA with inhibitors to hFVIII undergoing major or minor 
elective surgical, dental, or other invasive procedures as determined by the Global 
Hemostatic Efficacy Assessment (GHEA) score.
7.3 Secondary Objectives
The secondary objectives of the study are to:
1. To determine the safety of BAX802 used in the perioperative setting by assessing:
The development of and change in titer of anti-pFVIII and anti-hFVIII inhibitory 
antibodies (binding and/or neutralizing), and development of binding antibodies 
to BHK proteins
The occurrence of thrombotic events and/or allergic reactions to BAX802
The occurrence of AEs related to BAX802
The occurrence of clinically significant changes in vital signs and routine 
laboratory parameters related to BAX802
2. To determine the intra- and postoperative blood loss at the end of surgery, compared 
to the estimated volume of expected average and maximum blood loss in a 
comparable healthy individual as predicted preoperatively by the 
investigator/surgeon
3. To determine the daily and total weight-adjusted administration of BAX802 per 
subject
4. To determine the blood product utilization 
5. To determine the occurrence of bleeding episodes during the intra- and postoperative 
periods and additional need for surgical intervention
6. To evaluate any intercurrent, unrelated bleeding episodes in the postoperative period.
For non-commercial use only

BAX802
Page 26 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8. STUDY DESIGN
8.1 Brief Summary
This study is a Phase 3, uncontrolled, open-label, single-group, multicenter study to 
determine the safety and efficacy of BAX802 in 10 male subjects with CHA with 
inhibitors to hFVIII who are undergoing major or minor elective surgical, dental, or other 
invasive procedures.
8.2 Overall Study Design 
This study is a Phase 3, prospective, open-label, uncontrolled, multicenter study to 
evaluate the efficacy and safety of BAX802 in at least 10 evaluable male subjects with 
CHA with inhibitors to hFVIII who are undergoing major and minor surgical, dental or 
other invasive procedures. At least 5 of the procedures must be major surgeries in 
5 evaluable subjects (see Section 8.2.1).
The dose and frequency of BAX802 during the preoperative, intraoperative, and 
postoperative periods should follow a substitution plan provided by the investigator prior 
to surgery and adjusted based on regular FVIII activity measurements. The regimen will 
depend on the type of surgery performed and the intensity of the hemostatic challenge.
Elective surgical procedures will prospectively be defined as major or minor by the 
investigator/surgeon and agreed with the medical director/designee, based on the protocol 
guidance and definitions and in consideration of each subject’s characteristics. 
Emergency surgeries are not in the scope of this study. Subjects may undergo more than 
1 surgery or 2 parallel surgeries, such as bilateral knee replacement, however, in these 
cases prior approval by the sponsor is required.
The study will be conducted globally and will be divided into 5 periods: Screening, 
Preoperative, Intraoperative, Postoperative, and End of study (Table 8).
The overall study design is illustrated in Figure 1. 
8.2.1 Types of Interventions
Elective procedures will prospectively be defined by the investigator/surgeon as major or 
minor based on the definitions and examples provided in Section 8.2.1.1 and 
Section 8.2.1.2 taking into consideration each individual patient’s characteristics and 
agreement with the sponsor. 
For non-commercial use only

BAX802
Page 27 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.2.1.1 Major Surgeries
Major surgeries include surgeries that require moderate or deep sedation, general 
anesthesia, or major conduction blockade for patient comfort. This generally refers to 
major orthopedic (eg, joint replacement), major abdominal, intracranial, cardiovascular, 
spinal and any other surgery which has a significant risk of large volume blood loss 
(> 500 mL) or blood loss into a confined anatomical space. Several tooth extractions or 
extraction of the third molar are generally considered as major. Examples include:

bone fixation for fracture

hip and knee replacement (arthroplasty)

arthrodesis (joint fusion)

open synovectomy

osteotomy

liver biopsy

pseudotumor removal

hardware removal (plates, intramedullary nails)
Major surgeries/interventions are expected to require clinical surveillance or hospital 
treatment > 3 days after the surgery/intervention. 
8.2.1.2 Minor Surgeries
Minor surgeries include surgeries that can be safely and comfortably performed on a 
patient who has received local or topical anesthesia, without more than minimal 
preoperative medication or minimal preoperative medication or minimal intraoperative 
sedation. The estimated total blood loss should be < 500 mL and the likelihood of 
complications requiring hospitalization or prolonged hospitalization should be remote. It 
refers to interventions such as removal of skin lesions, arthroscopy, minor dental 
procedures or dental extractions. Examples include:

removal of skin lesions

minor dental procedures or dental extractions (except extraction of several teeth or 
third molar extraction)

placement and/or removal of central venous catheters

synoviorthesis and arthrocentesis
For non-commercial use only

BAX802
Page 28 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

arthroscopy

nerve release

removal of osteophytes and small cysts 
Minor surgeries/interventions are expected to require clinical surveillance or hospital 
treatment ≤3 days after the surgery/intervention
8.2.2 Dose Selection Rationale
Background
This is a Phase 3, open label study of the efficacy and safety of B-domain deleted rpFVIII 
(BAX802) in the perioperative management of hemostasis in subjects with CHA who 
have inhibitors and are undergoing surgical or other invasive procedures. The rpFVIII 
temporarily replaces the inhibited FVIII that is needed for effective hemostasis in CHA 
patients who have developed inhibitors to hFVIII. The principle of using pFVIII is based 
on its low cross-reactivity with anti-hFVIII antibodies due to sequence variations 
between human and pFVIII in the A2 and C2 domains, the main targets of FVIII 
inhibitors. The rpFVIII concentrate is predicted to have an advantage over human-derived 
FVIII in CHA patients who have inhibitors since previous studies demonstrated that the 
antibodies have a median of only 15% cross-reactivity with plasma-derived porcine 
FVIII.18  
Regulatory approval for rpFVIII for the treatment of bleeding episodes in adults with 
AHA was received for OBIZUR®; per the product label, the initial dose of OBIZUR® is 
200 U/kg, with subsequent dosing dependent on the location and severity of bleeding 
episode, target factor VIII levels, and the patient’s clinical condition.17
Influence of Anti-pFVIII Inhibitor Titer on the Loading Dose
Anti-pFVIII inhibitors are neutralizing antibodies against pFVIII that neutralize the 
pFVIII, and thereby reduce its hemostasis effect. Anti-pFVIII inhibitors can be quantified 
in plasma by the Bethesda assay, which measures the ability of the patient’s plasma to 
neutralize exogenous pFVIII when incubated together.  
The amount of pFVIII required to neutralize the anti-pFVIII activity is factored in. A BU 
is defined as the amount of anti-pFVIII inhibitor in a plasma sample which will neutralize 
50% of 1 unit of pFVIII in normal plasma after 2 hour incubation at 37°C. 
For non-commercial use only

BAX802
Page 29 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Only the inhibitor that is distributed in the plasma volume (PV) is initially available to 
neutralize the infused FVIII; PV is calculated using the following formula: 
PV = Blood Volume x (1 – [hematocrit{Hct}%/100])
Normal blood volume is approximately 80 mL/kg for adults.
Therefore, PV = 80 x (1 – [Hct%/100]).
One BU of anti-pFVIII inhibitor will neutralize 50% of 1 unit of pFVIII; therefore, it is 
assumed that 0.5 U FVIII will be required for each 1 BU of inhibitor. The amount of 
BAX802 required to neutralize the anti-pFVIII activity can be estimated using the 
following:
Body weight x 80(1 - [Hct%/100]) x 0.5 x anti-pFVIII titer (BU) = 
body weight x 40(1-[Hct%/100]) x anti-pFVIII titer (BU).
Proposed Dosing Regimen of BAX802 in Study BAX802 Surgery
This regimen for loading dose of BAX802 proposed for Study BAX802 Surgery takes 
into account the titer of anti-pFVIII inhibitors. This regimen for loading dose of BAX802 
proposed for Study BAX802 Surgery takes into account the titer of anti-pFVIII 
inhibitors. The dosing scheme to be used in Study BAX802 Surgery is presented in 
Section 8.7.3.3.
The loading dose of BAX802 for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
80 U/kg + body weight x 40(1-[Hct%/100]) x anti-pFVIII titer (BU)
For example, for a 70 kg subject undergoing major surgery and having hematocrit 45% 
and anti-pFVIII titer 3 BU, the loading dose of BAX802 will is calculated as follows: 
80 (70) + 70 x 40(1-[45/100]) x 3 = 10,220 U
This dosing scheme should reasonably predict the loading dose before surgery that will 
provide sufficient FVIII levels needed for effective hemostasis.
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved (Table 5).
For non-commercial use only

BAX802
Page 30 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
This dosing algorithm is essentially equivalent to that proposed by Kasper (2004) when 
using FVIII in the treatment of patients with low titer inhibitors.19
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study will be approximately 20 months from study initiation 
(ie, first subject enrolled) to study completion (ie, last subject, last visit). The recruitment 
period is expected to be 13 to 16 months.  
The duration of subject participation depends on the nature of the invasive procedure: it 
will run from the signing of the informed consent until completion of the End of Study 
Visit up to 6 weeks post-surgery (surgery = Day 0), unless prematurely discontinued. 
Study completion is defined by the End of Study Visit after discharge.
8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is the GHEA score (Table 1), which is composed of 
3 individual ratings:
Assessment of intraoperative hemostatic efficacy of BAX802 performed by the 
operating surgeon (see Table 2)
Assessment of postoperative hemostatic efficacy of BAX802 at postoperative 
Day 1 (approximately 24 hours after surgery) performed by the operating surgeon 
(see Table 3)
Assessment of postoperative hemostatic efficacy of BAX802 at Day 14, performed 
by the investigator (see Table 4)
The scores of each of the 3 individual ratings described above, will be added together to 
form a GHEA score according to Table 1. For a GHEA score of 7 to be rated “excellent” 
no individual assessment score should be less than 2 (i.e. one individual assessment score 
must be 3 and the other two individual assessment scores must be 2). The only other 
option to achieve a GHEA score of 7 is for two individual assessment scores of 3 and one 
individual assessment score of 1. Although this GHEA score will not qualify for a rating 
of “excellent,” the GHEA score will satisfy the definition of “good,” (with no individual 
assessment score less than 1). All possible combinations of the individual assessment 
scores and their related ratings are provided in Supplement Section 20.6. Missing scores 
will be counted as 0.
For non-commercial use only

BAX802
Page 31 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 1: Global Hemostatic Efficacy Assessment (GHEA)
Assessment
GHEA Score
Excellent
7a to 9
(with no category scored < 2)
Good
5 to 7a
(with no category scored < 1)
Fair
3 to 4
(with no category scored < 1)
None
0 to 2 (or at least one category scored 0)
a
For a GHEA score of 7 to be rated “excellent” (with no individual assessment scores less than 2), at 
least 1 individual assessment score must be 3 and the other 2 individual assessment scores must be 
at least 2; otherwise a score of 7 is rated “good”.
Table 2: Intraoperative Efficacy Assessment Scale
A
At the time of discharge from the OR, the operating surgeon will assess the 
intraoperative hemostatic efficacy
Rating
Criteria
Score
Excellent
Intraoperative blood loss was less than or equal to that expected for the 
type of procedure performed in a non-hemophilic population (≤100%)
3
Good
Intraoperative blood loss was up to 50% more than expected for the type 
of procedure performed in a non-hemophilic population (101 - 150%)
2
Fair
Intraoperative blood loss was more than 50% of that expected for the 
type of procedure performed in a non-hemophilic population (> 150%)
1
None
Uncontrolled hemorrhage that was the result of inadequate therapeutic 
response despite proper dosing, necessitating rescue therapy 
0
Table 3: Postoperative Efficacy Assessment Scale (Postoperative Day 1)
B
On postoperative Day 1, the operating surgeon will assess the postoperative 
hemostatic efficacy by the operating surgeon
Rating
Criteria
Score
Excellent
Postoperative blood loss was less than or equal to (≤100%) that 
expected for the type of procedure performed in a non-hemophilic 
population
3
Good
Postoperative blood loss was up to 50% more (101% - 150%) than 
expected for the type of procedure performed in a non-hemophilic 
population 
2
Fair
Postoperative blood loss was more than 50% (> 150%) of that expected 
for the type of procedure performed in a non-hemophilic population 
1
None
Significant postoperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy 
0
For non-commercial use only

BAX802
Page 32 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 4: Postoperative Efficacy Assessment Scale (Day 14)
C
At Day 14, a hematologist will assess the postoperative efficacy
Rating
Criteria
Score
Excellent
Postoperative blood loss was less than or equal to (≤100%) that 
expected for the type of procedure performed in a non-hemophilic 
population,
Required blood components for transfusions were less than or similar to 
that expected in non-hemophilic population
3
Good
Postoperative blood loss was up to 50% more (101% - 150%) than 
expected for the type of procedure performed in a non-hemophilic 
population
Required blood components for transfusions were less than or similar to 
that expected in non-hemophilic population
2
Fair
Postoperative blood loss was more than 50% of that expected for the 
type of procedure performed in a non-hemophilic population (> 150%)
Required blood components transfusions were greater than that expected 
in non-hemophilic population
1
None
Significant postoperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy 
Required blood components for transfusions were substantially greater 
than that expected in non-hemophilic population
0
8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy 
1.
Intra- and postoperative blood loss compared to the estimated volume of expected 
average blood loss and expected maximum blood loss in a comparable healthy 
individual as predicted preoperatively by the investigator/surgeon at the following 
time points:
Intraoperative, at the end of surgery
Postoperative Day 1, approximately 24 hours after surgery
Postoperative Day 14 
2.
Daily and total weight-adjusted administration of BAX802 per subject
3.
Volume of blood, red blood cells, platelets, and other blood products transfused
4.
Occurrence of bleeding episodes during the intra- and postoperative periods and 
additional need for surgical intervention
5.
Efficacy of the treatment of intercurrent, unrelated bleeding episodes in the 
postoperative period.
For non-commercial use only

BAX802
Page 33 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2.2 Safety
1.
Development of, and changes to, the titer of inhibitory and binding antibodies to 
rpFVIII
2.
Development of, and changes to, the titer of inhibitory and binding antibodies to 
hFVIII
3.
Development of binding antibodies to BHK proteins
4.
Occurrence of thrombotic events
5.
Incidence of severe allergic reactions (eg, anaphylaxis)
6.
Incidence of other IP-related AEs
7.
Incidence of clinically significant changes in vital signs and routine laboratory 
parameters (hematology, clinical chemistry)
8.5 Randomization and Blinding
This is a non-randomized, open-label, active treatment clinical study.
8.6 Study Stopping Rules 
The study will be halted (enrollment stopped), pending further review by the internal 
Safety Monitoring Committee (iSMC) and sponsor, if one or more of the following 
criteria are met:
1.
Two or more subjects develop a severe anaphylactoid reaction or any other 
serious adverse event (SAE) related to BAX802 that would not be expected with a 
currently licensed rpFVIII product (OBIZUR®)
2.
Other AEs that are deemed to pose unacceptable risks to subjects.
The study may be terminated, if one or more of the following criteria are met:
1.
The sponsor decides to terminate the study based upon iSMC recommendation or 
its own assessment of safety
2.
The sponsor decides to terminate the study at any time for administrative reasons.
8.7 Investigational Product(s)
BAX802 will be supplied as white lyophilized powder in 3 mL glass vials containing 
nominally 500 units per vial for reconstitution with 1.0 mL sterile water for injection. 
For non-commercial use only

BAX802
Page 34 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.1 Packaging, Labeling, and Storage
BAX802 will be supplied in a lyophilized form. For specific instructions for 
reconstitution, please refer to the Study Manual. A sufficient quantity of BAX802 will be 
supplied to each study site, as well as an acknowledgement of receipt form.
The core label texts for all packaging units will be translated or adjusted, to be in 
compliance with applicable regulatory requirements, national laws in force and in 
accordance with the local languages. Minimally each vial will bear a label with the 
following information:
Sponsor name
Study number
Pharmaceutical dosage form
Route of administration
Name of IMP and actual quantity of dose units
Batch number
Space on which to record the subject number
The statement ‘For clinical trial use only’ or ‘Caution: new drug limited by Federal 
Law to investigational use’ or ‘To be used only by a qualified investigator’, as 
appropriate
Name, address and telephone number of the Sponsor, Contract Research 
Organization (CRO) or investigator, if appropriate
Storage conditions
Expiry or manufacturing date, as appropriate
The investigator or designee will only dispense BAX802 to subjects included in this 
study.
8.7.2 Reconstitution and Administration
The reconstitution procedures for BAX802 are detailed in the Pharmacy Manual. 
Reconstituted BAX802 should be kept and administered at room temperature and must be 
administered within 3 hours of reconstitution.
BAX802 will be administered as an intravenous infusion per the dosing schema for major 
and minor surgeries (Table 5).
For non-commercial use only

BAX802
Page 35 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3 Description of Treatment
8.7.3.1 FVIII Maintenance Plan
Based on the category (minor or major) and type of surgery, the investigator must outline 
the expected FVIII maintenance plan with target peak and trough levels covering the 
surgical, dental or invasive procedure until expected wound healing. The FVIII 
maintenance plan will be provided to the medical director/designee to ensure that the 
recommendations regarding FVIII target levels as provided in the protocol are followed. 
Each FVIII maintenance plan for major surgeries requires prior approval of the medical 
director. The FVIII levels measured intra/postoperatively will be compared with the 
FVIII maintenance plan. Slight deviations from the predefined substitution plan are 
allowed based on investigators clinical judgment and available laboratory FVIII data.
8.7.3.2 Perioperative Dosing
Adjustments to the dose and frequency of BAX802 dosing during the intra- and 
postoperative period should follow the maintenance plan provided by the investigator 
prior to surgery. Adjustments must be based on regular FVIII activity measurements 
determined at pre- and post-dosing of BAX802 and will depend on the type of the 
surgery performed and the intensity of the hemostatic challenge.
8.7.3.3 Dosing Schedule and Requirements
8.7.3.3.1 General
The dose and frequency of BAX802 administered will be individualized based on the 
subject’s PK parameters for major surgeries and the most recent IR value for minor 
surgeries and the required FVIII target levels. 
As described in Section 8.2.2, the loading dose will be calculated according to the 
following formula:
Loading Dose of BAX802:
Major Surgery: 80 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII titer 
(BU), administered approximately 1 hour prior to the surgery
Minor Surgery: 50 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII titer 
(BU), administered approximately 1 hour prior to the surgery
The loading dose of BAX802 for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
80 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII titer (BU)
For non-commercial use only

BAX802
Page 36 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For example, for a 70 kg subject undergoing major surgery and having hematocrit 45% 
and anti-pFVIII titer 3 BU, the loading dose of BAX802 will be calculated as follows: 
80 (70) + 70 x 40(1-[45/100]) x 3 = 10,220 U
Subsequent doses, dosing frequency, and duration of treatment will be based on the 
clinical judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved based on the following calculation (Table 5):
Required dose (IU) = 
[body weight (kg) x desired FVIII rise (IU/dL or % of normal)]/1.2 (IU/kg per IU/dL).
Table 5: Dosing for Perioperative Management
Type of 
Surgery
Factor VIII Level Required
(% of normal or IU/dL)
Loading Dose
Subsequent Dose
Major
(see 
Section 8.2.1.1)
Prior to surgery: ≥80%
Postoperative up to 72 hours 
(Day 1- Day 3): ≥80%
Postoperative Day 4 – Day 7: 
≥50% (if not yet discharged)
Postoperative Day 8 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels should not 
fall below 30% (left to the 
discretion of the investigator 
depending on the postoperative 
course)
80 U/kg + body weight 
(kg) x 40(1-[Hct%/100]) x 
anti-pFVIII titer (BU)1, 
administered 
approximately 1 hour prior 
to the surgery
Titrate subsequent 
doses to maintain 
recommended FVIII 
trough levels and 
individual clinical 
response using 
following formula:
Required dose (IU) = 
[body weight (kg) x 
desired FVIII rise 
(IU/dL or % of 
normal)]/1.2 (IU/kg 
per IU/dL)
Minor 
(see 
Section 8.2.1.2)
Prior to surgery: ≥50%
Postoperative up to 72 hours 
(Day 1- Day 3): ≥50%
Postoperative Day 4 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels should not 
fall below 30% (left to the 
discretion of the investigator 
depending on the postoperative 
course)
50 U/kg + body weight 
(kg) x 40(1-[Hct%/100]) x 
anti-pFVIII titer (BU)1, 
administered 
approximately 1 hour prior 
to the surgery
1 pFVIII titer and hematocrit information available from screening lab result will be used.
Note: Plasma levels of FVIII should not exceed 200% of normal or 200 units per dL.
For non-commercial use only

BAX802
Page 37 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If at any time during the study, a subject does not respond to BAX802 therapy as 
anticipated either by the operating surgeon or hemophilia physician providing 
postoperative care, blood samples will be drawn for the determination of FVIII activity 
levels. In the event of unexplained, excessive bleeding, the subject will be treated by 
whatever means necessary until adequate hemostasis is achieved. If other rescue 
medications become necessary, the subject will subsequently be withdrawn from this 
BAX802 surgery study. Adverse events and the details of concomitant medication and 
blood product use coincident with the treatment of all unanticipated bleeding will be 
recorded. The use of adjunct antifibrinolytic therapy (such as tranexamic acid) is allowed 
if clinically indicated by the investigator and/or according to the standard of care of the 
subject’s institution.
8.7.3.3.2 Preoperative and Loading Dose
The subject will receive a loading dose calculated according to the formula described 
above in order to maintain a minimum target FVIII level as required by the category and 
type of surgery. The recommended loading dose will be calculated by the investigator. 
The initial loading dose will be administered within 60 minutes prior to surgery (prior to 
incision/intubation). 
In case of major surgery, FVIII target levels should be ≥80% of normal, in case of minor 
surgery FVIII levels should be at ≥50%.
The surgery may only start after FVIII levels are in the target levels.
ALL subsequent dosing of BAX802 should be preceded by measurement of residual 
FVIII levels and dose adjustments must be based on the most recent residual FVIII 
activity levels. 
Note: Plasma levels of FVIII should not exceed 200% of normal or 200 units per dL.
Note: Dose adjustments based on aPTT values are not allowed.
8.7.3.3.3 Postoperative Dosing
Major Surgery
After the initial loading dose, an optional re-bolus sufficient to raise FVIII levels to the 
appropriate level as defined for the type of surgery may be administered after a blood 
sample for FVIII determination has been drawn and the required FVIII levels by the local 
laboratory have been determined. 
For non-commercial use only

BAX802
Page 38 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Note:
A second FVIII activity level must be determined within preferably 6-8 hours 
following major surgery and within 12 hours at the latest, with dose adjustments as 
necessary on the day of surgery. 
ALL subsequent dosing of BAX802 must be preceded by measurement of residual 
FVIII levels and the dose adjusted as needed. Dosing adjustments based on aPTT 
values are not allowed.
Any modifications of the FVIII maintenance recommendations and the substitution plan 
that are deemed necessary during the postoperative period will be at the discretion of the 
investigator and will be documented on the eCRFs. 
Beginning on postoperative Day 1 (ie, the day following the day of surgery) through 
discharge, subjects will have a BAX802 pre-dosing (within 30 minutes) and after 
15 ±5 minutes a post-dosing FVIII level measurement at least once per day in order to 
assess the adequacy of BAX802 therapy during the postoperative period. For consistency, 
it is recommended that the daily blood draws are performed at the same time of the day, 
such as morning blood draws.
8.7.3.3.4 Dosing for Unrelated Bleeding Episodes During the Postoperative Period
Unrelated bleeding episode is defined in Section 11.2.5. 
The BAX802 dosing regimen for treatment of these bleeding episodes will be based on 
the guidelines in Table 6. These guidelines may be adjusted by the investigator based 
upon his or her clinical judgment.
It is critical that treatment of a bleed is initiated as soon as possible after occurrence 
of the bleeding episode.
Repeat infusions of BAX802 can be administered to treat these bleeding episodes, as per 
investigator’s discretion.
When bleeding is controlled, additional infusions of BAX802 to maintain hemostasis are 
permitted, if required. Infusions given to maintain hemostasis should be documented in 
the eCRF.
For a detailed description of bleeding episodes into different sites see Supplement 20.7. 
For non-commercial use only

BAX802
Page 39 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 6: BAX802 Treatment Guidelines for Unrelated Bleeding Episodes
Type of Bleeding 
Episode
FVIII Level 
Required (%)
Loading Dose
Subsequent Dose
Minor
Early hemarthrosis, mild 
muscle bleeding, or mild 
oral bleeding, including, 
epistaxis
20% to 40%
Loading dose (IU) = [body 
weight (kg) x desired FVIII 
rise (IU/dL or % of 
normal)]/1.5 (IU/kg per 
IU/dL) + body weight (kg) x 
40(1-[Hct%/100]) x anti-
pFVIII titer (BU) 1, 2
Titrate subsequent doses to 
maintain recommended FVIII 
trough levels and individual 
clinical response using 
following formula:
Required dose (IU) = [body
weight (kg) x desired FVIII 
rise (IU/dL or % of 
normal)]/1.5 (IU/kg per IU/dL)
Moderate
Moderate bleeding into 
muscles, bleeding into 
the oral cavity, definite 
hemarthrosis, and known 
trauma
30% to 60%
Major
Significant 
gastrointestinal bleeding, 
intracranial, intra-
abdominal, or 
intrathoracic bleeding, 
central nervous system 
bleeding, bleeding in the 
retropharyngeal or 
retroperitoneal spaces or 
iliopsoas sheath, 
fractures, head trauma
60% to 100%
1 pFVIII titer and hematocrit information available from Day 14 laboratory results (if available) will be 
used. If Day 14 laboratory results are not available, Screening laboratory results shall be used to make 
dosing calculations rather than waiting for Day 14 results.
2 BAX802 will not be used to treat these bleeding episodes if the Day 14 anti-pFVIII titer (if available) is 
> 10 BU.
Note: Plasma levels of FVIII should not exceed 200% of normal or 200 units per dL.
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics
Commercially available gelatin sponges, topical thrombin, fibrin sealants, absorbable 
collagen preparations or anti-fibrinolytics (eg, tranexamic acid, -amino caproic acid) 
may be used according to each institution’s standard of care. Details, including the dose, 
of all adjunctive hemostatic medication used will be recorded in the eCRFs designed for 
this study and the reason for use given. 
Thrombosis prophylaxis can be administered at the discretion of the investigator 
according to the standard of care of each institution and recorded into the respective 
eCRF. Thrombosis prophylaxis should preferably consist of mechanical measures such as 
intermittent pneumatic compression (IPC), compression stockings and early mobilization. 
For non-commercial use only

BAX802
Page 40 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Pharmacologic thrombosis prophylaxis such as low molecular weight heparin (LMWH) 
may be considered for certain surgical interventions such as major orthopedic surgery 
after careful evaluation by the investigator of the potential risks and benefits.
8.7.5 Investigational Product Accountability
The investigator will ensure that the IP(s) is stored as specified in the protocol and that 
the storage area is secured, with access limited to authorized study personnel. The 
investigator will maintain records that the IP(s) was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received and 
disposition. IP(s) must be dispensed only at the study site or other suitable location (eg, 
infusion center; home, as applicable per study design). Records will be maintained that 
includes the subject identification code (SIC), dispensation date, and amount dispensed. 
All remaining partially used and/or unused IP(s) will be returned to the sponsor or 
sponsor’s representative after study completion/termination, or destroyed with the 
permission of the sponsor in accordance with applicable laws and study site procedures.
If IP(s) is to be destroyed, the investigator will provide documentation in accordance with 
sponsor’s specifications.
8.8 Source Data
Per ICH GCP, source data are defined as all information in original records and certified 
copies of original records of clinical findings, observations, or other activities in a clinical 
trial that are necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents (original records or certified copies), which may be in 
paper and/or electronic format. Source data for this study comprise the following: 
hospital records, medical records, clinical and office charts, laboratory notes, memoranda, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical study.
For additional information on study documentation and CRFs, see Section 17.2.
For non-commercial use only

BAX802
Page 41 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subject is ≥ 18 to ≤ 65 years old at the time of screening
2.
Subject has provided signed informed consent
3.
Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤2%) 
CHA with inhibitors to human FVIII, as tested at screening at the central 
laboratory
4.
Subject requires elective surgery or other invasive procedures
5.
Subject is not currently receiving ITI therapy
6.
Subject has a Karnofsky performance score of ≥60
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable 
disease and CD4+ count ≥200 cells/mm3 at screening
8.
Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain 
reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease
9.
Subject is willing and able to comply with the requirements of the protocol.
9.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
The subject requires emergency surgery
2.
The subject’s weight is < 35 kg or > 120 kg
3.
Clinically symptomatic liver disease (eg, ≥5 X upper limit of normal alanine 
aminotransferase [ALT], as confirmed by central laboratory at screening, clinical 
evidence of portal hypertension, severe hypoalbuminemia or a documented 
prothrombin time/international normalized ratio (PT/INR) > 1.5)
4.
Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as 
confirmed by central laboratory at screening
5.
Anti-porcine inhibitor > 10 BU prior to surgery
6.
Platelet count < 100,000/µl
7.
Active condition of coagulation disorder such as von Willebrand disease
For non-commercial use only

BAX802
Page 42 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.
Planned use of α-interferon with or without ribavarin 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
9.
Known hypersensitivity to rpFVIII, or hamster or murine proteins
10. Subject has been exposed to an IP within 30 days prior to enrollment or is 
scheduled to participate in another clinical study involving an IP or 
investigational device during the course of this study
11. Unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the investigator.
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw (ie, reduce the degree of participation in the study) 
consent for continued participation and data collection. The reason for withdrawal will be 
recorded on the End of Study CRF. Assessments to be performed at the termination visit 
(including in cases of withdraw or discontinuation) are described in Section 10.7, 
Section 20.3, and Section 20.4.
Discontinuation (ie, complete withdrawal from study participation) may be due to 
dropout (ie, active discontinuation by subject) or loss to follow-up (ie, discontinuation by 
subject without notice or action). Additionally, the investigator and sponsor have the 
discretion to discontinue any subject from the study if, in their judgment, continued 
participation would pose an unacceptable risk for the subject.
Subjects also will be withdrawn from treatment or discontinued from further study 
participation for the following reasons:
AEs/SAEs that in the investigator or sponsor opinion, poses an unacceptable risk 
for continued dosing in the subject
The subject is determined by the sponsor or investigator to be noncompliant with 
administration of IP, despite evidence of retraining of the subject. The subject will 
be discontinued from further participation in the study
Participation in another clinical study involving an IP during the course of the study
The subject experiences a severe anaphylactic reaction
The subject had uncontrolled hemorrhage that was the result of inadequate 
therapeutic response despite proper dosing of rpFVIII, necessitating rescue therapy 
with bypassing agents.
For non-commercial use only

BAX802
Page 43 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10. STUDY PROCEDURES
10.1 Informed Consent and Enrollment
Any patient who provides informed consent (ie, signs and dates the informed consent 
form and assent form, if applicable) is considered enrolled in the study.
10.2 Subject Identification Code
The following series of numbers will comprise the SIC: protocol identifier (241502) to be 
provided by the sponsor, 2-digit number study site number (eg, 02) to be provided by the 
sponsor, and 3-digit subject number (eg, 003) reflecting the order of enrollment (ie, 
signing the informed consent form). For example, the third subject who signed an 
informed consent form at study site 02 will be identified as Subject 241502-02003. All 
study documents (eg, CRFs, clinical documentation, sample containers, drug 
accountability logs, etc.) will be identified with the SIC. Additionally, a uniquely coded 
SIC(s) is permitted as long as it does not contain a combination of information that 
allows identification of a subject (eg, collection of a subject’s initials and birth date 
would not be permitted), in compliance with laws governing data privacy.
10.3 Screening and Study Visits
The study site is responsible for maintaining an enrollment/screening log that includes all 
subjects enrolled. The log also will serve to document the reason for screening failure.
All screening data will be collected and reported in CRFs, regardless of screening 
outcome. If a subject is re-screened, the End of Study CRF should be completed, and a 
new informed consent form (ICF), new SIC and new CRF are required for that subject. 
Subjects who fail screening due to a single laboratory test result that does not meet 
eligibility criteria may have that laboratory test repeated at the discretion of the 
investigator. This will include a repeat of only the failed assessment; complete re-
screening will not be necessary. In these cases, a new SIC is not required; the subject will 
maintain their original SIC. The repeat of a screening assessment is allowed once. A 
repeat assessment must take place within 42 days of the initial screening for any subject 
requiring repeat of a screening assessment. If this timeframe is exceeded, then all 
screening assessments must be repeated and the subject assigned a new SIC. Exemptions 
are possible for administrative reasons and have to be approved by the sponsor. Subjects 
with an inadequate interval between screening and prior IP drug (other than BAX802) 
administration or prior participation in a drug or device study (ie, 30 days), may be re-
screened only once and only when the required interval is reached. 
For non-commercial use only

BAX802
Page 44 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The screening assessment should be performed within 45 days prior to the planned 
elective surgery.
The overall study design is illustrated in Supplement Figure 1. Details on the procedures 
to be performed at each study visit, including screening, can be found in Supplement 20.3
and Supplement 20.4.
10.4 Study Periods
The study will be divided into 5 periods: 
1.
Screening
2.
Preoperative 
3.
Intraoperative
4.
Postoperative
5.
End of study 
A detailed description of study procedures per study period is provided in 
Supplement 20.1.
10.4.1 Discharge/End of Study Visit
Discharge Visit will be performed when the subject is discharged and the End of Study 
Visit will be performed 42 to 49 days following the completion of the surgical procedure. 
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the 
End of Study visit, the respective visits will be done as a single visit.
10.4.2 Unscheduled Visits for Unrelated Bleeding Episodes
If the unrelated bleeding episode occurs after subject’s discharge, subject will visit the 
investigator (Table 11). If these unrelated bleeding episodes occur during the subject’s 
stay in hospital, subjects will be treated with BAX802. If these unrelated bleeding 
episodes occur after the subject has been discharged, subjects will be treated with 
BAX802 or with standard of care, as per investigator’s discretion. Follow up visits will 
be performed as per Table 11.
For non-commercial use only

BAX802
Page 45 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.5 Medications and Non-Drug Therapies 
The following medications are not permitted:
Medications:

Hemophilia inhibitor bypassing therapy (recombinant factor VIIa [NovoSeven] 
within 3 hours or aPCC [FEIBA)] within 6 hours prior to initial BAX802 
administration) unless used as a rescue medication (Section 10.5) after failure/study 
withdrawal

Hemophilia medication other than BAX802 at any time during the study. 
A subject who has taken any of these medications will be considered a protocol deviation.
The following medications and non-drug therapies are permitted within 30 days before 
study entry and during the course of the study:
Medications

The management of a serious thrombo-embolic event may require anticoagulant 
medication and this may need to be administered concurrent with the use of 
BAX802 to ensure that a re-bleed or continuing severe hemorrhage does not occur 
on withdrawal of BAX802 (see Section 10.6). In such instances the Sponsor’s 
medical monitor should be consulted.

Any medications deemed necessary by the subject’s physician to treat or prevent 
any medical condition (with the exception of those listed as not permitted)

Any over-the-counter medication used by the subject to treat symptoms or signs of 
any medical condition

Supplemental vitamins, minerals
Non-drug therapies:

Any non-drug therapy (eg, physiotherapy) deemed necessary by the subject’s 
physician to treat or prevent any medical condition
For non-commercial use only

BAX802
Page 46 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.6 Rescue Medications 
Bypassing agents (FEIBA or NovoSeven) can be used as a rescue medication if expected 
plasma FVIII activity levels are not attained or if bleeding is not controlled despite proper 
dosing of BAX802 during the intra- or postoperative period of the study. At least 2 doses 
of BAX802 needs to be administered before the subject is considered to be a treatment 
failure and switched to the rescue medication.
10.7 Subject Completion/Discontinuation
A subject is considered to have completed the study when he/she ceases active 
participation in the study because the subject has, or is presumed to have, completed all 
study procedures according with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation CRF, including: completed, screen failure, AE (eg, death), 
discontinuation by subject (eg, lost to follow-up [defined as 3 documented unsuccessful 
attempts to contact the subject], dropout), physician decision (eg, progressive disease, 
non-compliance with IP/protocol violation(s), recovery), study terminated by sponsor, or
other (reason to be specified by the investigator, eg, technical problems). Regardless of 
the reason, all data available for the subject up to the time of completion/discontinuation 
should be recorded on the appropriate CRF.
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit. If the completion/termination visit is done as an additional, 
unscheduled visit, the assessment results shall be recorded with the 
completion/termination visit. If a subject terminates participation in the study and does 
not return for the completion/termination visit, their last recorded assessments shall 
remain recorded with their last visit. The reason for discontinuation will be recorded, and 
the data collected up to the time of discontinuation will be used in the analysis and 
included in the clinical study report. If additional assessments are required, the 
assessments shall be recorded separately. Assessments to be performed at the termination 
visit (including in cases of withdraw or discontinuation) can be found in Supplement 20.3
and Supplement 20.4.
In the event of subject discontinuation due to an AE, clinical and/or laboratory 
investigations that are beyond the scope of the required study observations/assessments 
may be performed as part of the evaluation of the event. These investigations will take 
place under the direction of the investigator in consultation with the sponsor, and the 
details of the outcome may be reported to the appropriate regulatory authorities by the 
sponsor.
For non-commercial use only

BAX802
Page 47 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.8 Procedures for Monitoring Subject Compliance
Subject compliance with the procedures and treatment(s) outlined above will be 
monitored by direct review of the subject’s source data at the sites and evaluated against 
the protocol requirements. Additionally, electronic edit checks will be performed on all 
protocol-specified procedures and treatment data that are collected to ensure quality and 
accuracy. Deviations from the protocol-specified procedures and treatments will be noted 
in the final study report.
All study procedures are to be performed under the direct supervision of the 
investigator/a licensed healthcare professional at the study site, and thus, no separate 
procedures will be used to monitor subject compliance.
For non-commercial use only

BAX802
Page 48 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11. ASSESSMENT OF EFFICACY
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score
The primary outcome measure is the GHEA, which is composed of 3 individual 
categorical ratings which will be added together to form a GHEA score according to 
Table 1 (see Section 8.4.1).
11.2 Secondary Efficacy Endpoints
11.2.1 Blood Loss
The observed versus predicted operative blood loss will be described for the period from 
initiation of the intervention to discharge or 14 days after the intervention (whichever is 
first), as applicable.
Prior to the surgery, the surgeon/investigator will predict the estimated volume (in mL) of 
the expected average and maximum blood loss for the planned surgical intervention in a 
hemostatically normal individual of the same sex, age, and stature as the study subject, 
for intraoperative, postoperative, and overall perioperative time periods. Every effort 
should be made to predict the volume as precisely as possible, also taking into account, 
for example, the use of a tourniquet or placement of a postoperative drain and whether or 
not suction is used. The estimate will be for the intraoperative time period from 
completion of the procedure until approximately 24 hours post-surgery and for the overall 
perioperative time period (assessed at discharge or end of study visit).
The intraoperative blood loss will be measured by determining the volume of blood and 
fluid removal through suction into the collection container (waste box and/or cell saver) 
and the estimated blood loss into swabs and towels during the procedure, per the 
anesthesiologist’s record. Postoperatively, blood loss will be determined by the drainage 
volume collected, which will mainly consist of drainage fluid via vacuum or gravity 
drain, as applicable. In cases where no drain is present, blood loss will be determined by 
the surgeon’s clinical judgment, as applicable or entered as “not available”.
11.2.2 Blood Transfusions
The type and volume (in mL) of blood products will be recorded from initiation of the 
intervention to postoperative Day 14. Furthermore, also salvage of blood obtained from 
autologous transfusion systems, eg, cell savers, will be recorded. In addition, the type and 
volume of fluid replacement and volume expanders will be recorded as concomitant 
medication (eg, volume of salvaged blood, red blood cells, platelets and other blood 
products transfused)
For non-commercial use only

BAX802
Page 49 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.3 Bleeding Episodes
Any clinically relevant bleeding episodes (as assessed by the investigator), as well as the 
need for any further surgical interventions, will be recorded. Study subjects will be 
closely monitored for the occurrence of bleeding episodes during the entire intra- and 
postoperative period, until the time of discharge or until the subject resumes his previous 
treatment regimen, whichever is later. 
Any subject who is deemed to have excessive, unexplained bleeding will have blood 
drawn for measurement of FVIII levels. Treatment of such events should be performed as 
per standard of care at the institution.
11.2.4 BAX802 Administration
The daily and total weight-adjusted administration of BAX802 per subject will be 
recorded.
11.2.5 Hemostatic Efficacy Rating for Treatment of Inter-current, Unrelated 
Bleeding Episodes
An intercurrent, unrelated bleeding episode is defined as any bleeding occurring at a 
different anatomical site than the surgery site during the postoperative period. If these 
unrelated bleeding episodes occur during the subject’s stay in hospital, subjects will be 
treated with BAX802 (Note: BAX802 will not be used to treat these bleeding episodes if 
the Day 14 anti-pFVIII titer [if available] is > 10 BU). If these unrelated bleeding 
episodes occur after the subject has been discharged, subjects will be treated with 
BAX802 or with standard of care, as per investigator’s discretion. The dosing regimen is 
provided in Table 6.
If subject is treated with BAX802 for unrelated bleeding episodes, the subject will rate 
the severity (minor, moderate, or major) of the bleeding episode and will rate the overall 
treatment response at 24 ±2 hours after the initiation of treatment and at the resolution of 
bleed (if not resolved within 24 hours) using a 4-point efficacy rating scale (Table 7). 
Since the efficacy rating is based to a large degree on cessation of pain, the 
investigator/subject shall, in particular in case of injury-related bleeding into one or more 
than one location, consider the injury-related symptoms when performing the efficacy 
rating 24 hours after initiating treatment and at resolution of bleed.
As per Table 5, multiple infusions of BAX802 may be administered for the treatment of a 
bleeding episode. The overall response to all infusions combined is the rating that will be 
recorded at resolution of bleed.
For non-commercial use only

BAX802
Page 50 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 7: Efficacy Rating Scale for Treatment of Bleeding Episodes
Excellent
Full relief of pain and/or cessation of objective signs of bleeding (eg, swelling, 
tenderness, and decreased range of motion in the case of musculoskeletal 
hemorrhage) after a single infusion. No additional infusion is required for the 
control of bleeding. Administration of further infusions to maintain hemostasis 
would not affect this scoring.
Good
Definite pain relief and/or improvement in signs of bleeding after a single 
infusion. Possibly requires more than 1 infusion for complete resolution.
Fair
Probable and/or slight relief of pain and slight improvement in signs of bleeding 
after a single infusion. Required more than 1 infusion for complete resolution.
None
No improvement or condition worsens.
11.3 Factor VIII Activity
Blood will be obtained for assessment of FVIII activity at screening (tests to be 
performed at the central laboratory). Results from local laboratory will be used to 
make any dosing decisions.
Blood will be obtained for assessment of FVIII activity for patient management purposes 
at the following timepoints (tests to be performed at the local laboratory, with additional 
back-up samples to be tested in one batch at the central laboratory):
Within 60 minutes prior to the administration of the initial loading dose 
preoperatively and 15 ±5 minutes post-infusion. If a rebolus with BAX802 is 
required to obtain the required FVIII levels, an additional blood sample needs to 
be drawn 15 ±5 minutes following the rebolus with BAX802.
Postoperatively until day of discharge from the investigative site: daily within 
30 minutes prior to the infusion of BAX802 and 15 ±5 minutes post-infusion. 
Pre- and post-dosing blood draws for FVIII activity level determination should 
also be performed for each BAX802 administration.
FVIII activity will also be assessed if the subject has excessive, unexplained 
bleeding at any time intra-or postoperatively, or whenever deemed necessary 
according to the institution’s standard of care.
For non-commercial use only

BAX802
Page 51 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.3.1 Blood Sampling and Processing for FVIII Analysis
At each blood sampling time point whole blood will be collected in blood sampling tubes 
will be collected in S-Monovette® tubes (Sarstedt, Nümbrecht, Germany) containing 
3.2% trisodium citrate, or equivalent blood drawing equipment (eg, Vacutainer tubes), 
and immediately mixed. The citrated whole blood samples will be capped and transported 
at room temperature (ie, 20 - 25°C) to the local clinical laboratory for centrifugation, 
processing, and storage. Monovettes must be kept in an upright position at all times to 
avoid leakage.
All samples taken through 6 hours post-dosing will be collected from an extremity other 
than that used for the infusion of study product. Thereafter, either extremity may be used 
to obtain samples.
If the subject has a central venous catheter, the central line should be used to administer 
the infusion and a peripheral venipuncture should be used to collect the blood samples. 
In the event that a blood sample must be drawn through the central line used for 
administration of IP, the line must first be flushed with 5 mL normal saline or other 
suitable catheter flush solution that does not contain anticoagulant. At least 5 mL of 
whole blood must be collected and discarded prior to obtaining the sample. 
All citrated plasma samples will be stored and shipped to the central laboratory at 
≤-70°C for testing. 
All back-up samples collected during the perioperative period will be shipped to the 
central laboratory as soon as possible in one batch and analyzed, as needed. 
Blood samples will be analyzed for FVIII activity (1-stage clotting assay and the 
chromogenic assay) at the central laboratory. The 1-stage FVIII activity assay will serve 
as the primary assay; the chromogenic assay of FVIII activity will be used to provide
supportive data. Local laboratories are expected to use whichever FVIII assay is available 
(1-stage clotting assay or the chromogenic assay).
For non-commercial use only

BAX802
Page 52 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY
12.1 Adverse Events
12.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP 
that does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, 
bacteremia, etc.), or outcome of death temporally associated with the use of an IP, 
whether or not considered causally related to the IP.
12.1.1.1 Serious Adverse Event
A serious adverse event (SAE) is defined as an untoward medical occurrence that at any
dose meets one or more of the following criteria:
Outcome is fatal/results in death (including fetal death)
Is life-threatening – defined as an event in which the subject was, in the judgment 
of the investigator, at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death had it been more severe.
Requires inpatient hospitalization or results in prolongation of an existing 
hospitalization – inpatient hospitalization refers to any inpatient admission, 
regardless of length of stay.
Results in persistent or significant disability/incapacity (ie, a substantial disruption 
of a person’s ability to conduct normal life functions)
Is a congenital anomaly/birth defect
Is a medically important event – a medical event that may not be immediately
life-threatening or result in death or require hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the definitions above. Examples of such events are:
Intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependence or drug abuse.  
Reviewed and confirmed seroconversion for human immunodeficiency virus 
(HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus 
(HCV), hepatitis E virus (HEV), or parvovirus B19 (B19V)
For non-commercial use only

BAX802
Page 53 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Thromboembolic events (eg, stroke, myocardial infarction, deep vein 
thrombosis, pulmonary embolism)
Planned hospitalization for any study procedures as per the protocol will not be 
considered as an SAE.
12.1.1.2 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.3 Unexpected Adverse Events
An unexpected adverse event is an AE whose nature, severity, specificity, or outcome is 
not consistent with the term, representation, or description used in the Reference Safety 
Information (eg, IB, package insert). “Unexpected” also refers to the AEs that are 
mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation.
12.1.1.4 Preexisting Diseases
Preexisting diseases that are present before entry in to the study are described in the 
medical history, and those that manifest with the same severity, frequency, or duration 
after IP exposure, will not be recorded as AEs. However, when there is an increase in the 
severity, duration, or frequency of a preexisting disease, the event must be described on 
the AE CRF.
12.1.2 Assessment of Adverse Events
For the purposes of this study, the following non-serious events experienced after the first 
IP exposure are collected under other study endpoints and thus are not reportable on the 
AE CRF, nor will they be included in the analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they will 
be assessed as part of the efficacy assessments. However, the investigator may decide 
that the event is an AE if the event also would have occurred in a normal patient under 
the same circumstances. If a bleeding episode was caused by an injury, the injury will be 
reported as an AE.  
All other/Each AE from the first IP exposure until study completion or discontinuation 
date will be described on the AE CRF using the medical diagnosis (preferred), or, if no 
diagnosis could be established at the time of reporting the AE, a symptom or sign, in 
standard medical terminology in order to avoid the use of vague, ambiguous, or 
For non-commercial use only

BAX802
Page 54 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
colloquial expressions (see definition in Section 12.1). Each AE will be evaluated by the 
investigator for:
Seriousness as defined in Section 12.1.1.1
Severity as defined in Section 12.1.2.1
Causal relationship to IP exposure or study procedure as defined in Section 12.1.2.2
For each AE, the outcome (ie, recovering/resolving, recovered/resolved, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, unknown) and if 
applicable action taken (ie, dose increased, dose not changed, dose reduced, drug 
interrupted, drug withdrawn, not applicable, or unknown) will also be recorded on the AE 
CRF. Recovering/resolving AEs will be followed until resolution, medically stabilized, or
30 days after the study completion/termination visit, whichever comes first. If the 
severity rating for an ongoing AE changes before the event resolves, the original AE 
report will be revised (ie, the event will not be reported as separate AE). During the 
course of any AE, the highest severity rating will be reported.
Deviations from the protocol-specified dosage (including overdosing, underdosing, 
abuse, and withdrawal, treatment errors (including incorrect route of administration, use 
of an incorrect product, and deviations from the protocol-defined dosing schedule), 
failures of expected pharmacological actions, and unexpected therapeutic or clinical 
benefits will be followed with regard to occurrence of AEs, lack of efficacy, and/or other 
observations because these events may be reportable to regulatory authorities.
If an investigator becomes aware of an SAE occurring in a subject after study 
completion, the SAE must be reported on the provided SAE Report Form within 24 hours 
after awareness; no additional reporting on CRFs is necessary.
12.1.2.1 Severity
The investigator will assess the severity of each AE using his/her clinical expertise and 
judgment based on the most appropriate description below:
Mild
The AE is a transient discomfort and does not interfere in a significant manner 
with the subject’s normal functioning level.
The AE resolves spontaneously or may require minimal therapeutic 
intervention.
For non-commercial use only

BAX802
Page 55 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Moderate
The AE produces limited impairment of function and may require therapeutic 
intervention.
The AE produces no sequela/sequelae.
Severe
The AE results in a marked impairment of function and may lead to temporary 
inability to resume usual life pattern.
The AE produces sequela/sequelae, which require (prolonged) therapeutic 
intervention.
These severity definitions will also be used to assess the severity of an AE with a 
study-related procedure(s), if necessary.
12.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, eg, 
assessment of temporal relationships, dechallenge/rechallenge information, association 
(or lack of association) with underlying disease, presence (or absence) of a more likely 
cause, and physiological plausibility. For each AE, the investigator will assess the causal 
relationship between the IP and the AE using his/her clinical expertise and judgment 
according to the following most appropriate algorithm for the circumstances of the AE:
Not related (both circumstances must be met)
Is due to underlying or concurrent illness, complications, concurrent 
treatments, or effects of concurrent drugs
Is not associated with the IP (ie, does not follow a reasonable temporal 
relationship to the administration of IP or has a much more likely alternative 
etiology).
Unlikely related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists
Possibly related (both circumstances must be met)
Follows a reasonable temporal relationship to the administration of IP
An alternative etiology is equally or less likely compared to the potential 
relationship to the IP
For non-commercial use only

BAX802
Page 56 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Probably related (both circumstances must be met)
Follows a strong temporal relationship to the administration of IP, which may 
include but is not limited to the following:
o
Reappearance of a similar reaction upon re-administration (positive 
rechallenge)
o
Positive results in a drug sensitivity test (skin test, etc.)
o
Toxic level of the IP as evidenced by measurement of the IP 
concentrations in the blood or other bodily fluid
Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related, the investigator shall provide the 
alternative etiology. These causality definitions will also be used to assess the 
relationship of an AE with a study-related procedure(s), if necessary.
12.1.2.3 Safety Reporting
Adverse events/SAEs will be assessed at all study visits as outlined in the Schedule of 
Study Procedures and Assessments (see Table 9) and Section 12.1.
Adverse Events/SAEs are to be recorded on the AE page of the eCRF. Each event should 
be recorded separately.
Any SAE, including death due to any cause, which occurs during this study, whether or 
not related to the IP, must be reported immediately (within 24 hours of the study center’s 
first knowledge of the event). All SAEs must be reported via the Electronic Data Capture 
(EDC) system by completing the relevant electronic Case Report Form (eCRF) page(s) in 
English. Once the SAE has been recorded in the EDC system, the Sponsor and other 
designated recipients will be informed of the event automatically. For instances in which 
the EDC may become unavailable, SAEs must be reported using the back-up paper SAE 
Report Form to meet the 24 hour timeline requirement (contacts and instructions to be 
provided in separate documentation). Once the EDC becomes available, the site must 
enter all SAE data as reported on the back-up paper SAE report form on the applicable 
eCRF pages.
The initial SAE information reported on the applicable eCRF pages (or back-up SAE 
Report Form, if applicable) must at least include the following:
Protocol Number
For non-commercial use only

BAX802
Page 57 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Subject identification number and demographics (gender, age at onset of event 
and/or date of birth)
IP exposure
Medical Term for Event (Diagnosis preferably)
Description of the (S)AE, including:
Date of onset
(S)AE treatment (drug, dose, route of administration)
Causal relationship by the Investigator
Measures taken (ie, action taken regarding IP in direct relationship to the AE)
Seriousness criteria (ie, death, life-threatening, or other criterion)
Cause of death
Autopsy findings (if available)
Name, address, fax number, email, and telephone number of the reporting
Investigator (for paper SAE Report Forms)
12.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the 
protocol, in order to protect subjects participating in a clinical trial from immediate harm. 
Urgent safety measures may be taken by the sponsor or clinical investigator, and may 
include any of the following:
Immediate change in study design or study procedures
Temporary or permanent halt of a given clinical trial or trials
Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety
The investigator may take appropriate urgent safety measures in order to protect subjects 
against any immediate hazard to their health or safety. The measures should be taken 
immediately and may be taken without prior authorization from the sponsor. In the 
event(s) of an apparent immediate hazard to the subject, the investigator will notify the 
sponsor immediately by phone and confirm notification to the sponsor in writing as soon 
as possible, but within 1 calendar day after the change is implemented. The sponsor will 
also ensure the responsible ethics committee is notified of the urgent measures taken in 
such cases according to local regulations.
For non-commercial use only

BAX802
Page 58 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to IP are not 
considered AEs (according to the definition of AE, see Section 12.1). However, each 
serious untoward medical occurrence experienced before the first IP exposure (ie, from 
the time of signed informed consent up to but not including the first IP exposure) will be 
described on the AE CRF (and SAE Report Form if eCRF is not available). These events 
will not be considered as SAEs and will not be included in the analysis of SAEs.
For the purposes of this study, each of the following non-serious events experienced after 
the first exposure to IP will not be considered an AE, and thus, not included in the 
analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they 
will be assessed as part of the efficacy assessments. If a bleeding episode was 
caused by an injury, the injury would not be reported as an AE, unless it resulted in 
a medical finding other than a bleeding episode (eg, abrasion of skin). Therefore, 
any hemophilia-related event (eg, hemarthrosis [presenting as swelling, pain, and 
decreased range of motion], bruising, hemorrhages, or pain at bleeding episode site) 
will not be reported as AEs. However, the Investigator may decide that the event is 
an AE if the event also would have occurred in a normal patient under the same 
circumstances.
12.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to 
identity, quality, durability, reliability, safety and performance of the product but did not 
result in an AE. NMCs include but are not limited to the following:
A failure of a product to exhibit its expected pharmacological activity and/or design 
function, eg reconstitution difficulty
Missing components
Damage to the product or unit carton
A mislabeled product (eg, potential counterfeiting/tampering)
A bacteriological, chemical, or physical change or deterioration of the product 
causing it to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the 
sponsor within 1 business day. If requested, defective product(s) will be returned to the 
sponsor for inspection and analysis according to procedures.
For non-commercial use only

BAX802
Page 59 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.5 Medical, Medication, and Non-Drug Therapy History
At screening, the subject’s medical history will be described for the following body 
systems including severity (defined in Section 12.1.2.1) or surgery and start and end 
dates, if known: eyes, ears, nose, and throat; respiratory; cardiovascular; gastrointestinal; 
musculoskeletal; neurological; endocrine; hematopoietic/lymphatic; dermatological; and 
genitourinary.
Medical history will include the collection of hemophilia history, bleeding episode 
history, and history of aPCC or rFVIIA usage for 12 months prior to screening. Relevant 
medical and surgical history and all medications taken 3 months prior to screening will 
also be collected.
All medications taken and non-drug therapies received within 3 months before 
enrollment until completion/termination will be recorded on the concomitant medications 
and non-drug therapies CRFs.
12.6 Physical Examinations
At screening and subsequent study visits (as described in Table 9), a physical 
examination will be performed on the following body systems: general appearance, head 
and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and 
joints, lymph nodes, skin, and neurological. At screening, if an abnormal condition is 
detected, the condition will be described on the medical history CRF. At study visits, if a 
new abnormal or worsened abnormal pre-existing condition is detected, the condition will 
be described on the AE CRF. If the abnormal value was not deemed an AE because it 
was due to an error, due to a preexisting disease (described in Section 12.1.1.4), not 
clinically significant, a symptom of a new/worsened condition already recorded as an AE, 
or due to another issue that will be specified, the investigator will record the justification 
on the source record.
12.7 Clinical Laboratory Parameters
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, alanine aminotransferase, bilirubin, alkaline phosphatase, blood urea 
nitrogen, creatinine, and glucose.
The hematology panel will consist of complete blood count [hemoglobin, hematocrit, 
erythrocytes (ie, red blood cell count), and leukocytes (ie, white blood cell count)] with 
differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet 
counts.
For non-commercial use only

BAX802
Page 60 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Clinical chemistry and hematology assessments will be performed on EDTA-
anticoagulated serum and whole blood, respectively, at the central laboratory. The 
frequency of blood draws for clinical and hematology assessments is provided in 
Table 10. 
Details of blood sampling volumes are presented in the laboratory manual and master 
ICF.
12.7.1 Hematology, Clinical Chemistry, and Urinalysis
The hematology panel will consist of complete blood count (hemoglobin, hematocrit, 
erythrocytes [ie, red blood cell count], and leukocytes [ie, white blood cell count]) with 
differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet 
counts.
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, alanine aminotransferase, bilirubin, alkaline phosphatase, blood urea 
nitrogen, creatinine, and glucose.
Blood will be obtained for assessment of hematology and clinical chemistry parameters at 
screening/baseline, all study visits (ie, pre- and perioperatively and daily while the patient 
is at the study site), and at study completion/termination. Hematology and clinical 
chemistry assessments will be performed on EDTA-anticoagulated whole blood and 
serum, respectively, at the central or local laboratory.
The urinalysis panel will consist of pH, protein, ketones, glucose, bilirubin, blood, 
urobilinogen, specific gravity by dipstick and microscopy if any findings are abnormal.
Urine will be obtained for assessment of urinalysis parameters at screening and at study 
completion/termination.
12.7.2 Viral Serology
Viral serology testing will include HIV-1 and HIV-2 antibody, HAV antibody, 
HBV antibody, hepatitis B surface antigen (HBsAg), HCV antibody, and parvovirus B19 
(immunoglobulin M [IgM] and immunoglobulin G [IgG] antibodies). The HCV titer will 
be confirmed by PCR for all subjects reported as HCV positive. All viral serology 
assessments will be performed at screening. Any positive test will be repeated using a 
new blood sample.
For non-commercial use only

BAX802
Page 61 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7.3 Immunogenicity
Immunogenicity assessments will include anti-pFVIII and hFVIII binding and inhibitory 
and anti-BHK binding antibodies.
Blood samples will be collected for the assay of anti-pFVIII and hFVIII binding and 
inhibitory antibodies and anti-BHK binding antibodies at the times indicated in Table 9
and Table 10.
All FVIII and BAX802 inhibitor assays related to study subject management decisions by 
the investigator will be performed at the investigator’s local laboratory. Local 
laboratories will be pre-qualified for ability to provide these services prior to study 
participation. Further details for laboratory pre-qualification will be provided separately 
by the sponsor.
A central reference laboratory will perform assays (anti-pFVIII, anti-hFVIII, and anti-
BHK) on samples taken at the Screening, Day 14, and End of Study Visits.
Binding antibodies to pFVIII, hFVIII, and BHK, will be measured using ELISA. The 
assessment of inhibitory antibodies to porcine and hFVIII will be determined using a 
Bethesda assay (with the Nijmegen modification if possible). Further details on blood 
collection, tube preparation and shipment will be provided in the Study Manual.
12.7.4 Assessment of Laboratory Values
12.7.4.1 Assessment of Abnormal Laboratory Values
The investigator’s assessment of each laboratory value will be recorded on the CRF. For 
each abnormal laboratory value, the investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the investigator 
will indicate if the value constitutes an new AE (see definition in Section 12.1, and record
the sign, symptom, or medical diagnosis on the AE CRF), is a symptom or related to a
previously recorded AE, is due to a pre-existing disease (described in Section 12.1.1.4), 
or is due to another issue that will be specified. If the abnormal value was not clinically
significant, the investigator will indicate the reason, ie, because it is due to a preexisting 
disease, due to a lab error, or due to another issue that will be specified. Additional tests 
and other evaluations required to establish the significance or etiology of an abnormal 
value, or to monitor the course of an AE should be obtained when clinically indicated. 
Any abnormal value that persists should be followed at the discretion of the investigator.
For non-commercial use only

BAX802
Page 62 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7.5 Biobanking
Back up samples should be taken and stored appropriately for additional analysis, if 
necessary. These samples may be used for re-testing, further evaluation of an AE, or 
follow-up of other test results.
Samples are planned to be obtained at the following time points: Screening, Presurgery, 
Postoperative, Discharge, End of Study/Termination, and will be stored appropriately. 
This will ensure that there is sufficient material should any results require a re-test or 
additional testing (eg, further evaluation of an abnormal test or an AE).
Additional back up citrated plasma samples will be taken at each PK blood sampling time 
point to ensure if re-testing is required as well as possible additional assays for quality 
checks to comply with EMEA requirements there will be sufficient samples.
Backup samples that remain after study testing is done may be stored and used for 
additional testing of FVIII activity or safety parameters (eg, further evaluation of an 
abnormal test or an AE). Samples will be stored in a coded form for no more than 2 years 
after final study report completion and then the samples will subsequently be destroyed.
12.8 Vital Signs
Vital signs will include body temperature (°C or °F), respiratory rate (breaths/min), pulse 
rate (beats/min), and systolic and diastolic blood pressure (mmHg). Height (in or cm) 
measured once at screening, and weight (lb or kg) will also be collected. 
Vital signs will be measured at screening and within 30 minutes before and 
15 ±5 minutes after administration of IP, at each study visit, and at study
completion/termination. Blood pressure will be measured when subjects are in the
supine position.
Vital sign values are to be recorded on the CRF. For each abnormal vital sign value, the 
investigator will determine whether or not to report an AE (see definition in Section 12.1
and record the medical diagnosis (preferably), symptom, or sign on the AE CRF).
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
investigator.
For non-commercial use only

BAX802
Page 63 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.9 Karnofsky Performance Test
The Karnofsky Performance Test is a status scale (0 - 100) utilized to measure the level 
of activity and medical care requirements in subjects. It is an investigator based 
assessment of patient status which evaluates the subjects’ ability to carry on normal life 
activities, as well as the symptoms of their disease.20 Subjects will be scored using this 
scale at screening.
12.10 Special Treatment Considerations
Patients will be screened for eligibility in the study as described in the 
inclusion/exclusion criteria (Section 9.1 and Section 9.2), and will be informed of the 
study specific restrictions and requirements of the study. Patients who are not willing to 
comply with the study requirements and restrictions of the study will not be eligible for 
enrollment.
All biological agents carry the risk of systemic allergic/hypersensitivity reactions. 
Clinical manifestations of these reactions may include, but are not limited to:
skin rash
pruritus (itching)
urticaria (hives)
angioedema (for example, swelling of the lips and/or tongue)
anaphylactic reaction.
Proteins may also cause redness, itching, swelling, or pain locally at the infusion site.
Sometimes, these reactions can be life-threatening. Therefore, all patients should be 
closely monitored for signs or symptoms that could result from such reactions, educated 
on the signs or symptoms of these types of reactions, and instructed to contact the study 
site immediately if any of the symptoms are experienced following an injection. If a 
patient experiences an acute allergic/hypersensitivity reaction after an injection of 
investigational product, he or she should be managed appropriately and given instruction 
to receive relevant supportive care. Additionally, for an event judged by the investigator 
to be a potential systemic allergic/hypersensitivity reaction, a blood sample should be 
drawn to test for anti-drug antibodies.
Patients who experience a potentially severe allergic reaction will be discontinued from 
study drug, they will complete a Termination/Study Completion Visit, and will be 
monitored for stabilization, or resolution of the AE. Premedications to prevent allergic 
reactions will not be permitted as severe allergic reactions are an outcome measure for 
this study. 
For non-commercial use only

BAX802
Page 64 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. STATISTICS
Data handling will be the responsibility of the contract research organization (CRO). The 
data will be inspected for inconsistencies by performing validation checks.
All details regarding the statistical analysis and the preparation of tables, listings, and 
figures will be described in the statistical analysis plan (SAP) prepared by the CRO and 
approved by the sponsor before database lock. 
13.1 Sample Size and Power Calculations
The sample size of at least 10 evaluable male subjects, 5 of which must have major 
surgery as defined in the protocol, was chosen to provide sufficient evidence of safety 
and effectiveness for this indication and is not based on statistical considerations.
13.2 Datasets and Analysis Cohorts
Classification into the analysis sets will be conducted prior to the database lock.
13.2.1 Safety Analysis Set
The safety analysis set (SAS) will be comprised of all subjects who received any amount 
of BAX802.
13.2.2 Efficacy Datasets
13.2.2.1 Full Analysis Set 
The full analysis set (FAS) will comprised of all subjects with at least one available 
hemostatic assessment.
13.2.2.2 Per-Protocol Analysis Set
The per-protocol analysis set (PP) will comprise all subjects with available perioperative 
hemostatic efficacy assessed by:
i)
the operating surgeon within 60 minutes post-surgery
ii)
postoperative hemostatic control assessed by the operating surgeon 
postoperatively at 24 hours, and
iii) postoperative hemostatic control assessed by the investigator during Day 14. 
Only subjects who met all study entry criteria and who had no major protocol violations 
that might impact hemostatic efficacy assessments will be included in the PP analysis set.
For non-commercial use only

BAX802
Page 65 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.3 Handling of Missing, Unused, and Spurious Data
All data will be evaluated as observed; no imputation method for missing values will be 
used. A subject who withdraws prior to the last planned observation in a trial period will 
be included in the analyses up to the time of withdrawal.
13.4 Methods of Analysis
For qualitative parameters, the population size (N for sample size and n for available 
data) and the percentage (of available data) for each class of parameters will be 
presented. Quantitative parameters will be summarized by the population size (N for 
sample size and n for available data), mean, standard deviation, median, minimum, and 
maximum values.
13.4.1 Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy 
assessed intraoperatively by the surgeon and postoperatively by the investigator 
(hemophilia physician) at postoperative Day 1 (ie, the day following the day of surgery) 
and at postoperative Day 14 visit, and will be summarized by the GHEA score and rated 
“excellent”, “good”, “moderate” and “none”.
A treatment success will be defined as a rating of excellent and/or good. 
Point estimates and corresponding two-sided exact confidence intervals (CIs) at the 90% 
confidence level will be calculated for the rate of hemostatic efficacy assessments with 
excellent/good outcome.
The primary efficacy analysis will be based on the FAS. As a supportive analysis, the 
same calculations will also be carried out on the PP population.
13.4.2 Secondary Outcome Measures 
13.4.2.1 Secondary Hemostatic Efficacy Analysis
Descriptive statistics will be used to summarize the actual blood loss and transfusion 
requirements, respectively. 
The summary of average daily and total weight-adjusted doses (average through 
postoperative Day 14) of BAX802 per subject as well as the occurrence of bleeding 
episodes will be provided using descriptive statistics. 
For non-commercial use only

BAX802
Page 66 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For intercurrent, unrelated bleeding episodes in the postoperative period, descriptive 
statistics will be used to summarize the overall hemostatic efficacy rating at 24 ±2 hours 
after initiation of treatment and at resolution of bleed (if not resolved within 24 hours). 
The secondary efficacy analysis will be performed on the FAS only.
13.4.2.2 Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by presenting the number and percentage of subjects 
having any AE, having an AE in each system organ class, and having each individual AE 
as reported by preferred term. In the summaries, AEs will be counted only once per 
patient. If a patient reports the same AE more than once, it will be counted with its worst 
severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the 
number of IP-related AEs will be tabulated and subcategorized for thrombotic events, 
inhibitory and total binding antibodies to rpFVIII and hFVIII, and binding antibodies to 
BHK proteins.
A listing of all AEs will be presented by subject identifier, age, preferred term, and 
reported term of the AE, duration, severity, seriousness, action taken, outcome, causality 
assessment, onset date, stop date, and medication or non-drug therapy to treat the AE. An 
overview table for AEs will be provided, presenting the number of AEs, the number of 
subjects with AEs and the corresponding percent of subjects in total, and by seriousness 
and relationship to study treatment. An additional summary table will present the total 
number of (mild, moderate, severe) AEs by system organ class and preferred term with 
relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. 
Descriptive statistics of changes from baseline (Day 0 - prior to surgery) by study visits 
will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. 
Furthermore, laboratory abnormalities will be analyzed by shift tables where each subject 
will be counted only once with the worst grade in the summary tables. 
All laboratory data will be listed with abnormal values.
For non-commercial use only

BAX802
Page 67 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Vital signs assessments as well as the corresponding changes from baseline will be 
summarized descriptively at each scheduled assessment.
The safety analysis will be based on the SAS.
13.5 Planned Interim Analysis of the Study
Interim analyses may be conducted, as needed, for this study.
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The investigator/study site will cooperate and provide direct access to study documents 
and data, including source documentation for monitoring by the study monitor, audits by
the sponsor or sponsor’s representatives, review by the EC, and inspections by applicable 
regulatory authorities, as described in the Clinical Study Agreement. If contacted by an 
applicable regulatory authority, the investigator will notify the sponsor of contact, 
cooperate with the authority, provide the sponsor with copies of all documents received 
from the authority, and allow the sponsor to comment on any responses, as described in 
the Clinical Study Agreement.
For non-commercial use only

BAX802
Page 68 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable regulatory requirements as described in the 
Clinical Study Agreement. The investigator is ultimately responsible for the conduct of 
all aspects of the study at the study site and verifies by signature the integrity of all data 
transmitted to the sponsor. The term “investigator” as used in this protocol as well as in 
other study documents, refers to the investigator or authorized study personnel that the 
investigator has designated to perform certain duties. Sub-investigators or other 
authorized study personnel are eligible to sign for the investigator, except where the 
investigator’s signature is specifically required.
15.1.1 Investigator Report and Final Clinical Study Report
The investigator, or coordinating investigator(s) for multicenter studies, will sign the 
clinical study report. The coordinating investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the investigator and study site personnel understand all 
requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an investigator. Training may be provided at an investigator’s meeting, 
at the study site, and/or by instruction manuals. In addition, the study monitor will be 
available for consultation with the investigator and will serve as the liaison between the 
study site and the sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts 
the study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable regulatory guidelines/requirements. 
The investigator will permit the study monitor to visit the study site at appropriate 
intervals, as described in the Clinical Study Agreement. Monitoring processes specific to 
the study will be described in the clinical monitoring plan.
15.4 Auditing
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable regulatory guidelines/requirements. 
The investigator will permit auditors to visit the study site, as described in the Clinical 
Study Agreement. Auditing processes specific to the study will be described in the 
auditing plan.
For non-commercial use only

BAX802
Page 69 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15.5 Non-Compliance with the Protocol
The investigator may deviate from the protocol only to eliminate an apparent immediate 
hazard to the subject. In the event(s) of an apparent immediate hazard to the subject, the 
investigator will notify the sponsor immediately by phone and confirm notification to the 
sponsor in writing as soon as possible, but within 1 calendar day after the change is 
implemented. The sponsor (Baxalta) will also ensure the responsible ethics committee is 
notified of the urgent measures taken in such cases according to local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the sponsor may terminate the investigator’s participation. The sponsor will 
notify the EC and applicable regulatory authorities of any investigator termination.
15.6 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments. Local 
laboratories are requested to provide their laboratory specifications for each assay used.
For non-commercial use only

BAX802
Page 70 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16. ETHICS 
16.1 Subject Privacy
The investigator will comply with applicable subject privacy regulations/guidance as 
described in the Clinical Study Agreement.
16.2 Ethics Committee and Regulatory Authorities
Before enrollment of patients into this study, the protocol, informed consent form, any
promotional material/advertisements, and any other written information to be provided 
will be reviewed and approved/given favorable opinion by the EC and applicable 
regulatory authorities. The IB will be provided for review. The EC’s composition or a 
statement that the EC’s composition meets applicable regulatory criteria will be 
documented. The study will commence only upon the sponsor’s receipt of 
approval/favorable opinion from the EC and, if required, upon the sponsor’s notification 
of applicable regulatory authority(ies) approval, as described in the Clinical Study 
Agreement.
If the protocol or any other information given to the subject is amended, the revised 
documents will be reviewed and approved/given favorable opinion by the EC and 
applicable regulatory authorities, where applicable. The protocol amendment will only be 
implemented upon the sponsor’s receipt of approval and, if required, upon the sponsor’s 
notification of applicable regulatory authority(ies) approval.
16.3 Informed Consent
Investigators will choose patients for enrollment considering the study eligibility criteria. 
The investigator will exercise no selectivity so that no bias is introduced from this source.
All patients and/or their legally authorized representative must sign an ICF before 
entering into the study according to applicable regulatory requirements and ICH GCP. An 
assent form may be provided and should be signed by patients less than 18 years of age. 
Before use, the ICF will be reviewed by the sponsor and approved by the EC and
regulatory authority(ies), where applicable, (see Section 16.2). The ICF will include a 
comprehensive explanation of the proposed treatment without any exculpatory
statements, in accordance with the elements required by ICH GCP and applicable 
regulatory requirements. Patients or their legally authorized representative(s) will be 
allowed sufficient time to consider participation in the study. By signing the ICF, patients 
or their legally authorized representative(s) agree that they will complete all evaluations 
required by the study, unless they withdraw voluntarily or are terminated from the study 
for any reason.
For non-commercial use only

BAX802
Page 71 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The sponsor will provide to the investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The ICF will be 
updated, if necessary. This new information and/or revised informed consent form that 
has been approved by the applicable EC and regulatory authorities, where applicable, will 
be provided by the investigator to the subjects who consented to participate in the study
(see Section 16.3).
16.4 Internal Safety Monitoring Committee
This study will be monitored by an internal Safety Monitoring Committee (iSMC). The 
iSMC will be comprised of Baxalta individuals with pertinent expertise that will review 
accumulating data from this study on a regular basis. For this study, the iSMC will be 
composed of individuals from Drug Safety/Pharmacovigilance, Clinical Research, 
Clinical Development, Data Management, and Biostatistics, who are not actively
involved in this study. The iSMC will provide recommendations based on the available 
data. Details regarding iSMC are provided in the Safety Review Plan.
For non-commercial use only

BAX802
Page 72 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The investigator will comply with the confidentiality policy as described in the Clinical 
Study Agreement. 
17.2 Study Documentation and Case Report Forms
The investigator will maintain complete and accurate paper format study documentation 
in a separate file. Study documentation may include information defined as “source data” 
(see Section 8.8), records detailing the progress of the study for each subject, signed 
informed consent forms, correspondence with the EC and the study monitor/sponsor, 
enrollment and screening information, CRFs, SAE reports (SAERs), laboratory reports (if 
applicable), and data clarifications requested by the sponsor.
The investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry 
will be crossed out entirely, remaining legible; and 2) each correction must be dated and 
initialed by the person correcting the entry; the use of correction fluid and erasing are 
prohibited.
The investigator is responsible for the procurement of data and for the quality of data 
recorded on the CRFs. CRFs will be provided in electronic form.
If electronic format CRFs are provided by the sponsor, only authorized study site 
personnel will record or change data on the CRFs. If data is not entered on the CRFs 
during the study visit, the data will be recorded on paper, and this documentation will be 
considered source documentation. Changes to a CRF will require documentation of the 
reason for each change. An identical (electronic/paper) version of the complete set of 
CRFs for each subject will remain in the investigator file at the study site in accordance 
with the data retention policy (see Section 17.3).
The handling of data by the sponsor, including data quality assurance, will comply with 
regulatory guidelines (eg, ICH GCP) and the standard operating procedures of the 
sponsor. Data management and control processes specific to the study will be described 
in the data management plan.
17.3 Document and Data Retention 
The investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention 
policy, as described in the Clinical Study Agreement.
For non-commercial use only

BAX802
Page 73 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
18. FINANCING AND INSURANCE
The investigator will comply with investigator financing, investigator/sponsor insurance, 
and subject compensation policies, if applicable, as described in the Clinical Study 
Agreement.
19. PUBLICATION POLICY
The investigator will comply with the publication policy as described in the Clinical 
Study Agreement. 
For non-commercial use only

BAX802
Page 74 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. SUPPLEMENTS
20.1 Procedures per Study Period
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
1. Screening 
Written Informed Consent must be obtained prior to any study-related procedures
Screening activities should be performed within 45 days prior to the planned elective surgery.
The following screening procedures are required:

Eligibility evaluation (review of inclusion/exclusion criteria)

Hemophilia history, bleeding episode history, history of aPCC or rFVIIA usage for a year prior to 
screening

Relevant medical and surgical history and all medications taken 3 months prior to screening

Review of concomitant medications/non-drug therapies

Complete physical examination (see Section 12.6)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body weight 
and height; see Section 12.8)

Karnofskys performance test assessment (see Section 12.9)

Clinical laboratory assessments (see Table 10).
For non-commercial use only

BAX802
Page 75 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
2. Preoperative Procedures (Day 0)
Subjects will return to the study site prior to their scheduled surgery as instructed by site staff. Subjects will 
undergo the following procedures:
Prior to surgery
The following procedures should be performed before surgery and must be available by at the latest 2 hours 
before the start of surgery:

Accurate prediction of volume of expected blood loss intraoperatively (from completion of the 
procedure until approximately 24 hours post-surgery) and for the overall perioperative time period 
(up to discharge/end of study [EOS])
Loading Dose and Post Dosing Laboratory Assessment
Within 60 minutes before initiating surgery, the subject will receive a loading dose of BAX802 to raise the 
plasma level of FVIII to ≥80%  for major and to ≥50% for minor surgical, dental and invasive procedures.
Subjects will undergo the following procedures:

Prior to BAX802 loading dose:

Record AEs, concomitant medication and non-drug therapy use

Physical examination, vital signs (pulse, respiratory rate, blood pressure and temperature) and 
weight

Laboratory Assessments including:
o
Hematology (without differential but including platelets)
o
Clinical chemistry  
o
Within 15 - 30 minutes before loading dose, blood draw for:

FVIII activity 

BAX802 loading dose:

Loading dose of BAX802 to raise the plasma level of FVIII to ≥80% of normal for major and 
to ≥50% for minor surgical, dental and invasive procedures. It will be administered within 
60 minutes prior to surgery (prior to incision/intubation). 

After BAX802 loading dose:

Laboratory assessment of FVIII activity: 15 ±5 minutes after infusion of the loading dose

Vital signs (pulse, respiratory rate, blood pressure and temperature) will be recorded 
15 - 30 minutes after infusion

Confirmation that FVIII is adequate just prior to intubation/incision. Administration of 
additional dose of BAX802, if required. If another dose of BAX802 is necessary, an additional 
post-infusion FVIII activity determination must be performed 15 ±5 minutes following the 
infusion.

All samples taken through 6 hours post-infusion will be collected from an extremity other than 
that used for the infusion of study product. Thereafter, either extremity may be used to obtain 
samples.
The surgery can begin only if FVIII is in target range (Table 5).
Throughout: Monitoring of AEs and concomitant medication and non-drug therapy use.
For non-commercial use only

BAX802
Page 76 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
3. Intraoperative Procedures (Day 0)
During the surgical procedure:

Record AEs and concomitant medication and non-drug therapy use

Record blood product usage, including salvaged blood, packed red blood cells (pRBC), platelets, 
and other blood products. 

Administer additional BAX802 infusions according to the dosing regimen (Table 5) 

Record intraoperative blood loss and transfusion requirements
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary, the 
subject will subsequently be withdrawn from this BAX802 surgery study. 
After the surgical procedure:

Record the volume of blood loss during surgery and total blood product usage, including salvaged 
blood, packed red blood cells (pRBCs), platelets, and other blood products

Assess intraoperative hemostatic efficacy (Part A, Table 2) (at the end of surgery) 

Take sample for FVIII activity within preferably 6 - 8 hours following surgery and within 12 hours 
at the latest, with dose adjustments as necessary on the day of surgery (see Section 10.5)
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary (see 
Section 10.5), the subject will subsequently be withdrawn from this BAX802 surgery study.
For non-commercial use only

BAX802
Page 77 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
4. Postoperative Procedures (Days 1-13)

For subjects undergoing major surgery: keep pre-infusion FVIII levels at least at 80% of normal for 
the first postoperative 72 hours and at least at 50% during postoperative Day 4 to Day 7. From 
Day 8 until discharge, the FVIII levels should not fall below 30%.

For subjects undergoing minor surgery: keep pre-infusion FVIII levels at least at 50% of normal for 
the first postoperative 72 hours. From Day 4 until discharge, the FVIII levels should not fall below 
30%.
From Postoperative Day 1 (ie, the day following the day of the surgical/invasive procedure), 
and daily until discharge the following assessments will be performed:

Record AEs and concomitant medication and non-drug therapy use

Record blood loss on a daily basis and at drain removal, if applicable

Record transfusion requirements

Global Hemostatic Efficacy Assessment (GHEA):
o
Part B (Table 3): assessment of postoperative hemostatic efficacy of BAX802 performed 
at Day 1 by the operating surgeon/investigator
o
Part C (Table 4): assessment of perioperative hemostatic efficacy of BAX802 at Day 14 
performed by the investigator
If a subject leaves the facility on the day of the surgery/invasive procedure, it is required to 
have a site visit the next day (Day 1) and at Day 14 to perform the assessments of 
postoperative (Part B) and perioperative (Part C) hemostatic efficacy, respectively.

Perform physical examination and vital signs (pulse, respiratory rate, blood pressure and 
temperature) on Days 1, 2, 3, and 7 post surgery (if a subject remains admitted). 

Blood draws for FVIII activity determination and hematology should be performed coincident 
with an early morning dose to the greatest extent possible.

FVIII activity assays at the local and the central laboratories (back-up sample) at least once 
daily for Days 1 to 13. Additional BAX802 doses will be administered as per Table 5. FVIII 
activity assays pre infusion (within 30 minutes) and post infusion (15 ±5 minutes) for each IP 
administration, and at other time points as deemed necessary by the surgeon or investigator 
throughout the study 
o
1-stage clotting and chromogenic for the central laboratory
o
1-stage clotting or chromogenic (whichever is available) for local laboratories

Samples for laboratory testing will be taken daily during Day 1 to 7 post-surgery and then 
subsequently once weekly:
o
Hematology
o
Clinical chemistry

If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by 
whatever means necessary until adequate hemostasis is achieved. If rescue medications become 
necessary, the subject will subsequently be withdrawn from this BAX802 surgery study.
For non-commercial use only

BAX802
Page 78 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
5. Day 14 ±3 days Visit/Discharge Visit/End of Study [EOS] Visit (Day 42 +7 days)
The Day 14 Visit will be performed 14 days following completion of the surgical procedure, the Discharge 
Visit will be performed when the subject is discharged, and the EOS Visit will be performed 42 to 49 days 
following the completion of the surgical procedure. In cases where the Discharge Visit would occur within 
3 days of either the Day 14 or the EOS visit, the respective visits will be done as a single visit.
Procedures to be performed for each subject at Day 14 Visit/Discharge Visit/EOS Visit:

Perform Postoperative Hemostatic Efficacy Assessment (Part C) on Day 14 by the investigator 
(hemophilia physician)

Assessment of blood loss

Assessment of transfusion requirements

Review of concomitant medications/non-drug therapies

Complete physical examination 

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body 
weight)

Clinical laboratory assessments (Table 10)

Immunogenicity assays:

Anti-pFVIII and hFVIII binding and inhibitory antibody titers (Note: Before the blood draw 
for these assessments, at least 72 hours must have elapsed since the previous BAX802 
administration).

Anti-BHK binding antibody titers
Unrelated Bleeding Episodes During the Postoperative Period:
An intercurrent, unrelated bleeding episode is defined as any bleeding occurring at a different anatomical 
site than the surgery site during the postoperative period. If these unrelated bleeding episodes occur during 
the subject’s stay in hospital, subjects will be treated with BAX802. If these unrelated bleeding episodes 
occur after the subject has been discharged, subjects will be treated with BAX802 or with standard of care, 
as per investigator’s discretion. For unrelated bleeding episodes during the postoperative period, 
assessments will be collected as per Table 11.
For non-commercial use only

BAX802
Page 79 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.2 Study Flow Chart
Figure 1: Visit Schedule
For non-commercial use only

BAX802
Page 80 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.3 Schedule of Study Procedures and Assessments
Table 9: Schedule of Study Procedures and Assessments
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures; until 
subject is discharged
Day 14 ±3/ 
Discharge 
proceduresa
End of Study 
Visitb/ Discharge 
proceduresa
Procedure/Assessment
Up to 45 days 
prior to Day 0
Day 0
~2 hours prior 
to surgery
Day 0
During surgery
Day 1 to Day 13
Day 14 ±3
Discharge day
Day 42 +7
Discharge day
Eligibility criteria, including 
medical historyc
X
Medications and non-drug 
therapies
X
X
X
X
X
X
Physical examination
X
X
Xg (as required)
X
X
Adverse events
X
X
X
X
X
Laboratory assessmentsd
X
X
X
X
X
X
Vital signse
X
Xf
Xf
Xf,g
X
X
Karnofsky Performance Test
X
Approved FVIII maintenance 
plan
X
IP treatment
X (loading 
dose; Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
Hemostatic Efficacy 
Assessments
A as per Table 2
B at 24 hours (Day 1) 
as per Table 3h
C as per Table 4
Transfusion requirements
X
X
X
X
Continued on Next Page
For non-commercial use only

BAX802
Page 81 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
a
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the End of Study Visit, the respective visits will be done as a 
single visit.
b
This visit also applies to subjects who withdraw or discontinue prematurely.
c
Occurs at enrollment (prior to any study-specific procedures).
d
For laboratory assessments, see Table 10.
e
Vital signs will include body temperature, pulse rate, blood pressure, respiratory rate, and weight. Blood pressure will be measured when subjects 
are in the supine position. Height, measured once at Screening, will also be collected.
f
Within 30 minutes pre, 15 ±5 minutes post-dose
g
Perform physical examination and vital signs (pulse, respiratory rate, blood pressure and temperature) on Days 1, 2, 3, and 7 post surgery (if a 
subject remains admitted).
h
If the subject is discharged from surgical facility on the day of the procedure, he should attend the site on Day 1 to perform the postoperative 
hemostatic efficacy assessment. In this case, physical examination, vital signs, laboratory assessments, adverse events, and concomitant 
medications must also be assessed.
For non-commercial use only

BAX802
Page 82 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.4 Clinical Laboratory Assessments
Table 10: Clinical Laboratory Assessments
Preoperative 
Period
Postoperative Period
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
daily procedures; 
till subject is 
discharged
Day 14 ±3/ 
Discharge 
proceduresa
End of Study 
Visitb/ 
Discharge 
proceduresa
Assessment
Sample
Up to 
45 days prior 
to Day 0
Day 0
~2 hours Prior to 
Surgery
Day 0
During surgery
Day 1 to Day 13
Day 14 ±3
Discharge day
Day 42 +7
Discharge day
FVIII activity (clotting 
and chromogenic assay at 
central lab; either clotting 
or chromogenic assay at 
local lab)
Citrated 
plasma
C
L and B within 
30 minutes 
before loading 
dose, then 15 ±5 
minutes after 
loading dosec
Optional sampling, 
as deemed 
necessary: L and B
Also, if subject has 
excessive or 
unexplained 
bleeding
L and Bd
L and B
L and B
PT
Citrated 
plasma
C and L
Chemistrye
Serum
C
L and B
(L)
L
Daily Days 1 - 7
C (L)
C (L)
Hematology
Whole 
blood
C
L
(L)
L
Daily Days 1 - 7
C (L)
C (L)
Urinalysis
Urine
C
C
Viral serologyf
Serumg
C
Anti-pFVIII and hFVIII 
binding and inhibitory 
antibody titers
Citrated 
plasma
C
C (L)h
C (L)h
Anti-BHK binding 
Antibody titers
Citrated 
plasma
C
C (L)
C (L)
Continued on Next Page
For non-commercial use only

BAX802
Page 83 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
Key: C = central laboratory; L = local laboratory; (L) = local testing optional, to aid in clinical management of patients; 
B = back-up sample for central laboratory testing 
a
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the End of Study visit, the respective visits will be done as 
a single visit.
b
This visit also applies to subjects who withdraw or discontinue prematurely.
c
Surgery may take place only if FVIII is in target range (Table 5).
d
If underwent major surgery, take sample preferably within 6 to 8 hours following surgery, and within 12 hours at the latest. Sample at least once 
per day. FVIII activity assays pre infusion (within 30 minutes) and post infusion (15 ±5 minutes) for each IP administration, and at other time 
points as deemed necessary by the surgeon or investigator throughout the study. Also, if subject has excessive or unexplained bleeding as deemed 
necessary by the surgeon or investigator.
e
Sodium, potassium, chloride, bicarbonate, protein, albumin, alanine aminotransferase, bilirubin, alkaline phosphatase, blood urea nitrogen, 
creatinine, and glucose.
f
HIV-1 and HIV-2 antibody, HBsAb, HBsAg, HBcAb, and HCV Ab, CD4 for HIV positive patients and HCV-RNA or HIV-RNA for 
confirmatory testing of HIV or HCV positive results, respectively.
g
Citrated plasma for HCV-RNA or HIV-RNA confirmatory testing.
h
Before the blood draw for these assessments, at least 72 hours must have elapsed since the previous BAX802 administration.
For non-commercial use only

BAX802
Page 84 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.5 Schedule of Study Procedures and Clinical Laboratory Assessments for Unrelated Bleeding Episodes in the 
Postoperative Period
Table 11: Schedule of Study Procedures and Assessments for Unrelated Bleeding Episodes
Period
Sample 
(for lab 
assessments)
In-hospital or Unscheduled Visita
Follow-up Visits
At 24 ±2 hours after the initiation 
of treatment and
At the resolution of bleed (if not 
resolved within 24 hours)
Procedure/Assessment
Day 1 to End of Study Visit
As required
Medications and non-drug therapies
X
X
Physical examination
X
X
FVIII activity (clotting and chromogenic assay 
at central lab; either clotting or chromogenic 
assay at local lab)
Citrated plasma
L and B within 30 minutes before 
BAX802 dose, then 15 ± 5 min after doseb
L and Bb
Anti-pFVIII binding and inhibitory antibody 
titers
Citrated plasma
C (L)
Vital signs
Xc
Xc
IP treatmentd
X (as required; Table 6)
X (as required; Table 6)
Hemostatic Efficacy Assessments
X
as per Table 7
X
as per Table 7
Adverse events
X
X
Transfusion requirements
X
X
Key : C = central laboratory; L = local laboratory; (L) = local testing optional, to aid in clinical management of patients; 
B = back-up sample for central laboratory testing 
a
If the unrelated bleeding episode occurs after subject’s discharge, subject will visit the investigator and will be treated with BAX802 or with 
Standard of Care, as per investigator’s discretion. If these unrelated bleeding episodes occur during the subject’s stay in hospital, subjects will be 
treated with BAX802 (Note: BAX802 will not be used to treat these bleeding episodes if the Day 14 anti-pFVIII titer [if available] is > 10 BU). 
b
If another dose of BAX802 is necessary, an additional post-infusion FVIII activity determination must be performed 15 ±5 minutes following the 
infusion.
c
Within 30 minutes pre-dose, 15 ±5 minutes post-dose. 
d
If Day 14 anti-pFVIII titers and hematocrit are not available, the Screening lab results shall be used to make dosing calculations rather than waiting 
for Day 14 results..
For non-commercial use only

BAX802
Page 85 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.6 Global Efficacy Assessments Scores
Table 12: Combinations of Individual Efficacy Assessments
(A, B, C) and GHEA Score
Individual 
Assessment Scores
(A,B,C)
GHEA
3 3 3
Excellent
3 3 2
Excellent
3 2 2
Excellent
3 3 1
Good
3 2 1
Good
3 1 1
Good
2 2 2
Good
2 2 1
Good
2 1 1
Fair
1 1 1
Fair
3 3 0
None
3 2 0
None
3 1 0
None
3 0 0
None
2 2 0
None
2 1 0
None
2 0 0
None
1 1 0
None
1 0 0
None
0 0 0
None
For non-commercial use only

BAX802
Page 86 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.7 Definitions
20.7.1 Joint Bleeds
Features of an acute joint bleed include some or all of the following: ‘aura’, pain, 
swelling, warmth of the skin over the joint, decreased range of motion and difficulty in 
using the limb compared with baseline or loss of function. 
The earliest clinical signs of a joint bleed are increased warmth over the area and 
discomfort with movement, particularly at the ends of range.
Later symptoms and signs include pain at rest, swelling, tenderness, and extreme loss of 
motion.
In patients with advanced arthropathy it may be difficult to distinguish pain-related 
arthritis from that associated with an acute bleed. Rapid resolution of pain following 
infusion of factor concentrates (typical of an acute hemarthrosis) or improvement of pain 
associated with activity soon after a period of rest (typical of chronic arthritis) can help 
distinguish between the two.
20.7.2 Muscle Bleeds
Muscle bleeds can occur in any muscle of the body, usually from a direct blow or a 
sudden stretch. A muscle bleed is defined as an episode of bleeding into a muscle, 
determined clinically and/or by imaging studies, generally associated with pain and/or 
swelling and functional impairment over baseline.
For further definitions of CNS, GI and abdominal hemorrhages see the Guidelines for the 
management of hemophilia from the world federation of hemophilia.5,21
For non-commercial use only

BAX802
Page 87 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES
1. Coppola A, Di Capua M, Di Minno MND et al. Treatment of hemophilia: A review 
of current advances and ongoing issues. J.Blood Med. 2010;1:183-195.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262316/pdf/jbm-1-183.pdf
2. Janbain M, Leissinger CA, Kruse-Jarres R. Acquired hemophilia A: emerging 
treatment options. J.Blood Med. 2015;6:143-150.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431493/pdf/jbm-6-143.pdf
3. Mansouritorghabeh H. Clinical and laboratory approaches to hemophilia A. 
Iran.J.Med.Sci. 2015;40:194-205.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430880/pdf/ijms-40-194.pdf
4. Berntorp E, Shapiro A, Astermark J et al. Inhibitor treatment in haemophilias A and 
B: summary statement for the 2006 international consensus conference. 
Haemophilia. 2006;12 Suppl 6:1-7.
5. World Federation of Hemophilia Treatment Guidelines Working Group. Guidelines 
for the management of hemophilia 2nd Edtion.  76. 2005.  World Federation of 
Hemophilia (WFH). 
Link to Publisher´s Site: http://www1.wfh.org/publication/files/pdf-1472.pdf
For non-commercial use only

BAX802
Page 88 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. Santagostino E, Escobar M, Ozelo M et al. Recombinant activated factor VII in the 
treatment of bleeds and for the prevention of surgery-related bleeding in congenital 
haemophilia with inhibitors. Blood Rev. 2015;29 Suppl 1:S9-S18.
7. Valentino LA, Cooper DL, Goldstein B. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX. Haemophilia. 2011;17:11-579.
8. Kempton CL, White GC, II. How we treat a hemophilia A patient with a factor VIII 
inhibitor. Blood. 2009;113:11-17.
9. Kasper CK. Effect of prothrombin complex concentrates on factor VIII inhibitor 
levels. Blood. 1979;54:1358-1368.
10. Young G, Sørensen B, Dargaud Y et al. Thrombin generation and whole blood 
viscoelastic assays in the management of hemophilia: current state-of-art and future 
perspectives. Blood. 2013;121:1944-1950.
11. Kempton CL, Abshire TC, Deveras RA et al. Pharmacokinetics and safety of OBI-
1, a recombinant B domain-deleted porcine factor VIII, in subjects with 
haemophilia A. Haemophilia. 2012;18:798-804.
12. Mahlangu J, Andreeva T, Macfarlane D et al. A phase II open-label study 
evaluating the hemostatic activity, pharmacokinetics and safety of recombinant 
porcine factor VIII (OBI-1) in hemophlia A patients with inhbitors directed against 
human FVIII [abstract]. Haemophilia. 2008;14 Suppl 2:15-16.
For non-commercial use only

BAX802
Page 89 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. Kruse-Jarres R, St Louis J, Greist A et al. Efficacy and safety of OBI-1, an 
antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with 
acquired haemophilia A. Haemophilia. 2015;21:162-170.
14. Baxter Healthcare Corporation. Obizur core data sheet.  7-22-2015. 
15. Brettler DB, Forsberg AD, Levine PH et al. The use of porcine factor VIII 
concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor 
VIII. A multicenter US experience. Arch.Intern.Med. 1989;149:1381-1385.
16. Hay CRM, Lozier JN, Lee CA et al. Safety profile of porcine factor VIII and its use 
as hospital and home-therapy for patients with haemophilia-A and inhibitors: the 
results of an international survey. Thromb.Haemost. 1996;75:25-29.
17. Baxter Healthcare Corporation. Package Insert: OBIZUR [antihemophilic factor 
(recombinant), porcine sequence] lyophilized powder for solution for intravenous 
injection. 10. 2014. OBIZUR. 
18. Lee CA. The evidence behind inhibitor treatment with porcine factor VIII. 
Pathophysiol.Haemost.Thromb. 2002;32 Suppl 1:5-8.
19. Kasper, C. Diagnosis and Management of Inhibitors to Factors VIII and IX - An 
Introductory Discussion for Physicians. Treatment of Hemophilia(34), 22. 2004.  
World Federation of Hemophilia (WFH). 
Link to Publisher´s Site: http://www1.wfh.org/publications/files/pdf-1178.pdf
For non-commercial use only

BAX802
Page 90 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents 
in cancer. In: MacLeod CM, ed. Evaluation of Chemotherapeutic Agents. New 
York: Columbia University Press; 1949:191-205.
21. Blanchette VS, Key NS, Ljung LR et al. Definitions in hemophilia: Communication 
from the SSC of the ISTH. J.Thromb.Haemost. 2014;12:1935-1939.
For non-commercial use only

BAX802
Page 91 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX802
STUDY TITLE: A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety 
of B-Domain Deleted Recombinant Porcine Factor VIII (BAX802) in the Treatment 
of Patients with Congenital Hemophilia A with Factor VIII Inhibitors Undergoing 
Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
ORIGINAL: 2015 SEP 30
OTHER ID(s)
NCT Number: to be determined
EudraCT Number: to be determined
IND NUMBER: to be determined
By signing below, the investigator acknowledges that he/she has read and understands 
this protocol, and will comply with the requirements for obtaining informed consent from 
all study subjects prior to initiating any protocol-specific procedures, obtaining written 
initial and ongoing EC(s) protocol review and approval, understands and abides by the 
requirements for maintenance of source documentation, and provides assurance that this 
study will be conducted according to all requirements as defined in this protocol, clinical 
study agreement, ICH GCP guidelines, and all applicable regulatory requirements.
Signature of Principal Investigator
Date
Print Name of Principal Investigator
For non-commercial use only

BAX802
Page 92 of 92
Clinical Study Protocol Identifier: 241502
2015 SEP 30
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX802
STUDY TITLE: A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety 
of B-Domain Deleted Recombinant Porcine Factor VIII (BAX802) in the Treatment 
of Patients with Congenital Hemophilia A with Factor VIII Inhibitors Undergoing 
Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
ORIGINAL: 2015 SEP 30
OTHER ID(s)
NCT Number: to be determined
EudraCT Number: to be determined
IND NUMBER: to be determined
By signing below, the investigator acknowledges that he/she has read and understands 
this protocol, and provides assurance that this study will be conducted according to all 
requirements as defined in this protocol, clinical study agreement, ICH GCP guidelines, 
and all applicable regulatory requirements.
Signature of Coordinating Investigator
Date
Print Name and Title of Coordinating Investigator
Signature of Sponsor Representative
Date
, MD
, Clinical Development
For non-commercial use only

BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
CLINICAL STUDY PROTOCOL
PRODUCT: BAX 802
STUDY TITLE:
A Phase 3, Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of 
B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects with 
Congenital Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or Other 
Invasive Procedures
STUDY SHORT TITLE: BAX 802 in Congenital Hemophilia A with Inhibitors
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 1: 2016 FEB 03
Replaces: ORIGINAL: 2015 SEP 30
ALL VERSIONS: 
Amendment 1: 2016 FEB 03
Original: 2015 SEP 30
OTHER ID(s)
NCT Number:
to be determined
EudraCT Number:
to be determined
IND NUMBER: 
to be determined
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362, 
UNITED STATES
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna, 
AUSTRIA
For non-commercial use only

BAX 802
Page 2 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
, Clinical Development
Baxalta US Inc.
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with 
the study (eg, investigator(s), sponsor’s medical expert and study monitor, sponsor’s 
representative(s), laboratories, steering committees, and oversight committees (including 
ethics committees [ECs], as applicable) will be maintained by the sponsor and provided 
to the investigator.
For non-commercial use only

BAX 802
Page 3 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. SERIOUS ADVERSE EVENT REPORTING
The investigator will comply with applicable laws/requirements for reporting serious 
adverse events (SAEs) to the ECs.
ALL SAEs ARE TO BE REPORTED ON THE ADVERSE EVENT 
ELECTRONIC CASE REPORT FORM (eCRF) WITHIN 24 HOURS AFTER 
BECOMING AWARE OF THE EVENT. IF THE eCRF IS NOT AVAILABLE 
THEN THE SAE MUST BE REPORTED ON THE SERIOUS ADVERSE 
EVENT REPORT (SAER) FORM AND TRANSMITTED TO THE SPONSOR
TO MEET THE 24 HOUR TIMELINE REQIREMENT.
See SAE Protocol Sections for further information and SAER form for 
contact information.
Further details are also available in the study team roster.
For definitions and information on the assessment of these events, refer to the following:
1. AE, Section 12.1
2. SAE, Section 12.1.1.1
3. Assessment of AEs, Section 12.1.2
For non-commercial use only

BAX 802
Page 4 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
3. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of Investigational Product (IP)
BAX 802
Name(s) of Active Ingredient(s)
Recombinant Porcine Factor VIII
CLINICAL CONDITION(S)/INDICATION(S)
Congenital hemophilia A (CHA) patients with inhibitors to FVIII undergoing surgical and other invasive 
procedures
PROTOCOL ID
241502
PROTOCOL TITLE
A Phase 3, Multicenter, Open-label Study of the Efficacy and 
Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX 802) in Subjects with Congenital Hemophilia A with 
Factor VIII Inhibitors Undergoing Surgical or Other Invasive 
Procedures 
Short Title
BAX 802 in CHA with Inhibitors 
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2016, FEB
Primary Completion
2017, DEC 
Study Completion
2017, DEC 
Duration
20 months
STUDY OBJECTIVES AND PURPOSE
Study Purpose
To evaluate the efficacy and safety of BAX 802 in males with CHA with inhibitors who are undergoing 
major or minor elective surgical, dental, or other invasive procedures.
Primary Objective
To evaluate the perioperative hemostatic efficacy of BAX 802 in male subjects with CHA with inhibitors 
to human factor VIII (hFVIII) undergoing major or minor elective surgical, dental, or other invasive 
procedures as determined by the Global Hemostatic Efficacy Assessment (GHEA) score.
Secondary Objectives
1. To determine the safety of BAX 802 used in the perioperative setting by assessing:

The development of and change in titer of anti-pFVIII and anti-hFVIII inhibitory antibodies 
(binding and neutralizing), and development of binding antibodies to baby hamster kidney (BHK) 
proteins

The occurrence of thrombotic events and/or allergic reactions to BAX 802

The occurrence of adverse events (AEs) related to BAX 802

The occurrence of clinically significant changes in vital signs and routine laboratory parameters 
related to BAX 802
For non-commercial use only

BAX 802
Page 5 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. To determine the intra- and postoperative and overall perioperative blood loss at the end of surgery, 
compared to the estimated volume of expected average and maximum blood loss in a comparable 
healthy individual as predicted preoperatively by the investigator/surgeon
3. To determine the daily and total weight-adjusted administration of BAX 802 per subject
4. To determine the blood product utilization 
5. To determine the occurrence of bleeding episodes during the intra- and postoperative periods and 
additional need for surgical intervention
6. To evaluate any unrelated bleeding episodes in the postoperative period.
STUDY DESIGN
Study Type/ Classification/ 
Discipline
Efficacy and Safety
Control Type
No control
Study Indication Type
Treatment
Intervention model
single-group
Blinding/Masking
Open-label
Study Design
This study is a Phase 3, prospective, open-label, uncontrolled, 
multicenter study to evaluate the efficacy and safety of BAX 802 in at 
least 10 surgeries in 10 evaluable male subjects with CHA with inhibitors 
to hFVIII who are undergoing major and minor surgical, dental or other 
invasive procedures. At least 5 of the procedures must be major surgeries 
in 5 evaluable subjects.
Planned Duration of 
Subject Participation
The duration of subject participation depends on the nature of the invasive 
procedure: it will run from the signing of the informed consent until 
completion of the End of Study Visit (at least 6 weeks post-surgery 
[Day 0]).
Primary Outcome Measure 
The primary outcome measure is the GHEA score, which is composed of 3 individual ratings:

Assessment of intraoperative hemostatic efficacy of BAX 802 performed by the operating surgeon 

Assessment of postoperative hemostatic efficacy of BAX 802 at postoperative Day 1 (approximately 
24 hours after surgery) performed by the operating surgeon

Assessment of overall perioperative hemostatic efficacy of BAX 802 at Day 14 or discharge 
(whichever is earlier), performed by the investigator. 
The scores of each of the 3 individual ratings described above, will be added together to form a GHEA 
score.
For non-commercial use only

BAX 802
Page 6 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Secondary Outcome Measures 
Efficacy 
1. Blood loss compared to the estimated volume of expected average blood loss and expected maximum 
blood loss in a comparable healthy individual as predicted preoperatively by the investigator/surgeon 
at the following time points:

Intraoperative, at the end of surgery

Postoperative Day 1, approximately 24 hours after surgery

Overall perioperative Day 14 or discharge (whichever is earlier)
2. Daily and total weight-adjusted administration of BAX 802 per subject
3. Volume of blood, red blood cells, platelets, and other blood products transfused
4. Occurrence of bleeding episodes during the intra- and postoperative periods and additional need for 
surgical intervention
5. Efficacy of the treatment of unrelated bleeding episodes in the postoperative period. 
Safety
1. Development of, and changes to, the titer of inhibitory and binding antibodies to recombinant porcine 
factor VIII (rpFVIII)
2. Development of, and changes to, the titer of inhibitory and binding antibodies to hFVIII
3. Development of binding antibodies to BHK proteins
4. Occurrence of thrombotic events
5. Incidence of severe allergic reactions (eg, anaphylaxis)
6. Incidence of other IP-related AEs
7. Incidence of clinically significant changes in vital signs and routine laboratory parameters 
(hematology, clinical chemistry)
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Active Product
Dosage form: Injectable Reconstituted Solution
Dosage frequency: PRN = as needed
Mode of Administration: intravenous infusion
SUBJECT SELECTION
Targeted Accrual
Enroll 10 evaluable subjects
Number of 
Groups/Arms/Cohorts
1 arm
For non-commercial use only

BAX 802
Page 7 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Inclusion Criteria
1. Subject is ≥ 18 to ≤ 65 years old at the time of screening
2. Subject has provided signed informed consent
3. Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤ 2%) CHA with inhibitors 
to human FVIII, as tested at screening at the central laboratory
4. Subject requires elective surgery or other invasive procedures
5. Subject is not currently receiving or has recently received (< 30 days) ITI therapy
6. Subject has a Karnofsky performance score of ≥ 60
7. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and 
CD4+ count ≥ 200 cells/mm3 at screening
8. Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; 
or HCV+ with chronic stable hepatitis disease
9. Subject is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
1. The subject requires emergency surgery
2. The subject’s weight is < 35 kg or > 120 kg
3. Clinically symptomatic liver disease (eg, ≥ 5 X upper limit of normal alanine aminotransferase 
[ALT], as confirmed by central laboratory at screening, clinical evidence of portal hypertension, 
severe hypoalbuminemia or a documented prothrombin time/international normalized ratio [PT/INR] 
> 1.5)
4. Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as confirmed by central 
laboratory at screening
5. Anti-porcine inhibitor > 10 Bethesda units (BU) prior to surgery
6. Platelet count < 100,000/µL
7. Subject has another active coagulation disorder, other than hemophilia A, as per the medical history
8. Planned use of α-interferon with or without ribavarin 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
9. Known hypersensitivity to rpFVIII, or hamster or murine proteins
10. Subject has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in 
another clinical study involving an IP or investigational device during the course of this study
11. Unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the investigator 
For non-commercial use only

BAX 802
Page 8 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
STATISTICAL ANALYSIS
Sample Size Calculation
The sample size of at least 10 surgeries in 10 evaluable male subjects (at least 5 major surgeries in 
5 evaluable subjects), as defined in the protocol, was chosen to provide sufficient evidence of safety and 
effectiveness for this indication and is not based on statistical considerations. 
Planned Statistical Analysis
Analysis Sets
The safety analysis set (SAS) will be comprised of all subjects who received any amount of BAX 802. The 
full analysis set (FAS) will be comprised of all surgeries with at least 1 available hemostatic assessment. 
The per-protocol analysis set (PP) will be comprised of all surgeries with evaluable ratings for all 
3 perioperative hemostatic efficacy assessments, whom subjects met all study entry criteria and had no 
major protocol violations that might impact hemostatic efficacy assessments.
Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy assessed 
intraoperatively by the surgeon and postoperatively by the investigator (hemophilia physician) at 
postoperative Day 1 (ie, the day following the day of surgery) and perioperatively at postoperative Day 14 
visit or discharge (whichever is earlier), and will be summarized by the GHEA score and rated “excellent”, 
“good”, “fair” and “none”.
A treatment success will be defined as a rating of excellent and/or good. 
Owing the possibility of multiple surgeries per subject, the statistical entity on which the primary outcome 
measure will be reported is the surgery.
Point estimates and corresponding 2-sided exact confidence intervals (CIs) at the 90% confidence level will 
be calculated for the rate of hemostatic efficacy assessments with excellent/good outcome.
The primary efficacy analysis will be based on the FAS population. As a supportive analysis, the same 
calculations will also be carried out on the PP population.
Any blood loss which is considered as unrelated bleeding (defined as any bleeding occurring at a different 
anatomical site other than the surgery site during the postoperative period) will not be taken into account 
for while making assessment of hemostatic efficacy for the primary efficacy measure.
Secondary Outcome Measures
Secondary hemostatic efficacy analysis:
Where possible, secondary outcome measures will be reported at the surgery level rather than the subject
level. Descriptive statistics will be used to summarize the actual blood loss and transfusion requirements. 
The summary of average daily and total weight-adjusted doses (average through postoperative Day 14 or 
discharge [whichever is earlier]) of BAX 802 per subject as well as the occurrence of bleeding episodes 
will be provided using descriptive statistics. 
For non-commercial use only

BAX 802
Page 9 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For unrelated bleeding episodes in the postoperative period, descriptive statistics will be used to summarize 
the overall hemostatic efficacy rating at 24 ±2 hours after initiation of treatment and at resolution of bleed. 
The secondary efficacy analysis will be performed on the FAS only. Separate descriptive summaries of 
average daily and total weight-adjusted doses required to treat unrelated bleeding episodes and will be 
provided.
Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will 
be summarized by presenting the number and percentage of subjects having any AE, having an AE in each 
system organ class, and having each individual AE as reported by preferred term. In the summaries, AEs 
will be counted only once per patient. If a patient reports the same AE more than once, it will be counted 
with its worst severity and closest relationship to the study product.
The number of subjects who experienced serious adverse events (SAEs) and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the number of IP 
related AEs will be tabulated and subcategorized for thrombotic events, inhibitory and total binding 
antibodies to rpFVIII and hFVIII, and binding antibodies to BHK proteins.
An overview table for AEs will be provided, presenting the number of AEs, the number of subjects with 
AEs and the corresponding percent of subjects in total, and by seriousness and relationship to study 
treatment. An additional summary table will present the total number of (mild, moderate, severe) AEs by 
system organ class and preferred term with relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. Descriptive 
statistics of changes from baseline (Day 0 - prior to surgery) by study visits will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. Furthermore, laboratory 
abnormalities will be analyzed by shift tables where each subject will be counted only once with the worst 
grade in the summary tables.
Vital signs assessments as well as the corresponding changes from baseline will be summarized 
descriptively at each scheduled assessment.
For non-commercial use only

BAX 802
Page 10 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
4. TABLE OF CONTENTS
1. STUDY PERSONNEL ................................................................................................. 2
1.1 Authorized Representative (Signatory) / Responsible Party .............................. 2
1.2 Study Organization................................................................................................. 2
2. SERIOUS ADVERSE EVENT REPORTING........................................................... 3
3. SYNOPSIS..................................................................................................................... 4
4. TABLE OF CONTENTS ........................................................................................... 10
5. LIST OF ABBREVIATIONS .................................................................................... 15
6. BACKGROUND INFORMATION .......................................................................... 17
6.1 Description of Investigational Product ............................................................... 17
6.2 Clinical Condition/Indication .............................................................................. 17
6.3 Population to be Studied ...................................................................................... 19
6.4 Findings from Nonclinical and Clinical Studies................................................. 19
6.4.1 Finding from Nonclinical Studies................................................................. 19
6.4.2 Findings from Clinical Studies ..................................................................... 20
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 23
6.6 Compliance Statement.......................................................................................... 24
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 25
7.1 Study Purpose ....................................................................................................... 25
7.2 Primary Objective................................................................................................. 25
7.3 Secondary Objectives ........................................................................................... 25
8. STUDY DESIGN......................................................................................................... 26
8.1 Brief Summary...................................................................................................... 26
8.2 Overall Study Design............................................................................................ 26
8.2.1 Types of Interventions................................................................................... 26
8.2.1.1 Major Surgeries ...................................................................................... 27
8.2.1.2 Minor Surgeries ...................................................................................... 27
8.2.2 Dose Selection Rationale ............................................................................... 28
8.3 Duration of Study Period(s) and Subject Participation .................................... 30
8.4 Outcome Measures ............................................................................................... 30
8.4.1 Primary Outcome Measure .......................................................................... 30
8.4.2 Secondary Outcome Measures ..................................................................... 32
For non-commercial use only

BAX 802
Page 11 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2.1 Efficacy .................................................................................................... 32
8.4.2.2 Safety........................................................................................................ 33
8.5 Randomization and Blinding............................................................................... 33
8.6 Study Stopping Rules............................................................................................ 33
8.7 Investigational Product(s).................................................................................... 33
8.7.1 Packaging, Labeling, and Storage................................................................ 34
8.7.2 Reconstitution and Administration.............................................................. 34
8.7.3 Description of Treatment.............................................................................. 35
8.7.3.1 FVIII Maintenance Plan ........................................................................ 35
8.7.3.2 Perioperative Dosing .............................................................................. 35
8.7.3.3 Dosing Schedule and Requirements...................................................... 35
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics .................................... 41
8.7.5 Investigational Product Accountability ....................................................... 42
8.8 Source Data ........................................................................................................... 42
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 43
9.1 Inclusion Criteria.................................................................................................. 43
9.2 Exclusion Criteria................................................................................................. 43
9.3 Withdrawal and Discontinuation ........................................................................ 44
10. STUDY PROCEDURES .......................................................................................... 45
10.1 Informed Consent ............................................................................................... 45
10.2 Subject Identification Code................................................................................ 45
10.3 Screening and Study Visits................................................................................. 45
10.4 Study Periods....................................................................................................... 46
10.4.1 Discharge/End of Study Visit...................................................................... 46
10.4.2 Optional Antibody Testing Visit................................................................. 46
10.5 Medications and Non-Drug Therapies.............................................................. 47
10.6 Rescue Medications............................................................................................. 48
10.7 Subject Completion/Discontinuation ................................................................ 48
10.8 Procedures for Monitoring Subject Compliance............................................. 49
11. ASSESSMENT OF EFFICACY.............................................................................. 50
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score 50
11.2 Secondary Efficacy Endpoints........................................................................... 50
11.2.1 Blood Loss..................................................................................................... 50
11.2.2 Blood Transfusions ...................................................................................... 50
11.2.3 Bleeding Episodes ........................................................................................ 51
11.2.4 BAX 802 Administration............................................................................. 51
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated Bleeding 
Episodes.......................................................................................................... 51
11.3 Factor VIII Activity............................................................................................ 52
11.3.1 Blood Sampling and Processing for FVIII Analysis................................. 53
For non-commercial use only

BAX 802
Page 12 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY................................................................................... 54
12.1 Adverse Events.................................................................................................... 54
12.1.1 Definitions..................................................................................................... 54
12.1.1.1 Serious Adverse Event.......................................................................... 54
12.1.1.2 Non-Serious Adverse Event ................................................................. 55
12.1.1.3 Unexpected Adverse Events................................................................. 55
12.1.1.4 Preexisting Diseases.............................................................................. 55
12.1.2 Assessment of Adverse Events.................................................................... 55
12.1.2.1 Severity .................................................................................................. 57
12.1.2.2 Causality................................................................................................ 57
12.1.2.3 Safety Reporting ................................................................................... 58
12.2 Urgent Safety Measures ..................................................................................... 59
12.3 Untoward Medical Occurrences........................................................................ 60
12.4 Non-Medical Complaints ................................................................................... 60
12.5 Medical, Medication, and Non-Drug Therapy History................................... 61
12.6 Physical Examinations........................................................................................ 61
12.7 Clinical Laboratory Parameters........................................................................ 62
12.7.1 Hematology, Clinical Chemistry, and Urinalysis...................................... 62
12.7.2 Viral Serology............................................................................................... 63
12.7.3 Immunogenicity ........................................................................................... 63
12.7.4 Assessment of Laboratory Values .............................................................. 63
12.7.4.1 Assessment of Abnormal Laboratory Values..................................... 63
12.7.5 Backup Samples and Biobanking............................................................... 64
12.8 Vital Signs............................................................................................................ 64
12.9 Karnofsky Performance Test............................................................................. 65
12.10 Special Treatment Considerations .................................................................. 65
13. STATISTICS............................................................................................................. 66
13.1 Sample Size and Power Calculations ................................................................ 66
13.2 Analysis Sets........................................................................................................ 66
13.2.1 Safety Analysis Set....................................................................................... 66
13.2.2 Efficacy Datasets.......................................................................................... 66
13.2.2.1 Full Analysis Set.................................................................................... 66
13.2.2.2 Per-Protocol Analysis Set..................................................................... 66
13.3 Handling of Missing, Unused, and Spurious Data........................................... 66
13.4 Methods of Analysis............................................................................................ 67
13.4.1 Primary Outcome Measure......................................................................... 67
13.4.2 Secondary Outcome Measures ................................................................... 67
13.4.2.1 Secondary Hemostatic Efficacy Analysis ........................................... 67
13.4.2.2 Safety Analysis ...................................................................................... 68
13.5 Planned Interim Analysis of the Study ............................................................. 69
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 69
For non-commercial use only

BAX 802
Page 13 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 70
15.1 Investigator’s Responsibility.............................................................................. 70
15.1.1 Investigator Report and Final Clinical Study Report.............................. 70
15.2 Training ............................................................................................................... 70
15.3 Monitoring........................................................................................................... 70
15.4 Safety Monitoring ............................................................................................... 70
15.5 Auditing ............................................................................................................... 71
15.6 Non-Compliance with the Protocol ................................................................... 71
15.7 Laboratory and Reader Standardization ......................................................... 71
16. ETHICS ..................................................................................................................... 72
16.1 Subject Privacy ................................................................................................... 72
16.2 Ethics Committee and Regulatory Authorities................................................ 72
16.3 Informed Consent ............................................................................................... 72
17. DATA HANDLING AND RECORD KEEPING................................................... 74
17.1 Confidentiality Policy ......................................................................................... 74
17.2 Study Documentation and Case Report Forms ............................................... 74
17.3 Document and Data Retention........................................................................... 74
18. FINANCING AND INSURANCE........................................................................... 75
19. PUBLICATION POLICY........................................................................................ 75
20. SUPPLEMENTS....................................................................................................... 76
20.1 Procedures per Study Period............................................................................. 76
20.2 Study Flow Chart................................................................................................ 81
20.3 Schedule of Study Procedures and Assessments.............................................. 82
20.4 Clinical Laboratory Assessments ...................................................................... 84
20.5 Global Efficacy Assessments Scores.................................................................. 87
20.6 Definitions............................................................................................................ 88
20.6.1 Joint Bleeds................................................................................................... 88
20.6.2 Muscle Bleeds............................................................................................... 88
21. REFERENCES.......................................................................................................... 89
22. SUMMARY OF CHANGES.................................................................................... 93
INVESTIGATOR ACKNOWLEDGEMENT............................................................ 102
INVESTIGATOR ACKNOWLEDGEMENT............................................................ 103
For non-commercial use only

BAX 802
Page 14 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Tables
Table 1: Global Hemostatic Efficacy Assessment (GHEA)............................................. 31
Table 2: Intraoperative Efficacy Assessment Scale.......................................................... 31
Table 3: Postoperative Efficacy Assessment Scale (Postoperative Day 1) ...................... 31
Table 4: Overall Perioperative Efficacy Assessment Scale (Day 14)............................... 32
Table 5: Dosing for Perioperative Management............................................................... 36
Table 6: BAX 802 Treatment Guidelines for Unrelated Bleeding Episodes.................... 41
Table 7: Efficacy Rating Scale for Treatment of Unrelated Bleeding Episodes .............. 52
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502 ...... 76
Table 9: Schedule of Study Procedures and Assessments................................................ 82
Table 10: Clinical Laboratory Assessments ..................................................................... 84
Table 11: Combinations of Individual Efficacy Assessments (A, B, C) and GHEA Score
................................................................................................................................... 87
Figures
Figure 1: Visit Schedule.................................................................................................... 81
For non-commercial use only

BAX 802
Page 15 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
5. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
AICC
anti-inhibitor coagulant complex 
ALT
alanine aminotransferase
aPCC
activated prothrombin complex concentrate 
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
B19V
parvovirus B19
BHK
baby hamster kidney 
BU
Bethesda units
CI
confidence interval
CHA
Congenital Hemophilia A
CRF
case report form
CRO
Contract Research Organization 
EC
ethics committee
EBL
estimated blood loss
eCRF
electronic case report form
EDC
electronic data capture
FAS
full analysis Set 
GCP
Good Clinical Practice
GHEA
Global Hemostatic Efficacy Assessment 
HAV
hepatitis A virus
HBV
hepatitis B virus
Hct
hematocrit
HCV
hepatitis C virus
HEV
hepatitis E virus
hFVIII
human factor VIII 
HIV
human immunodeficiency virus
IB
Investigator’s brochure
ICF
informed consent form 
ICH
International Council for Harmonisation
IP
investigational product
IPC
intermittent pneumatic compression 
For non-commercial use only

BAX 802
Page 16 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Abbreviation
Definition
ISMC
internal safety monitoring committee 
ITI
immune tolerance induction
LMWH
low molecular weight heparin 
MedDRA
Medical Dictionary for Regulatory Activities 
NMC
Non-medical complaint
OR
operating room
PCR
polymerase chain reaction 
pFVIII
porcine factor VIII 
PP
Per Protocol (analysis set)
PRN
“pro re nata” (as needed)
PT/INR
prothrombin time/international normalized ratio 
PV
plasma volume
rhFVIII
recombinant human factor VIII 
rpFVIII
recombinant porcine factor VIII 
RSI
Reference Safety Information
SAE
serious adverse event
SAER
serious adverse event report
SAP
statistical analysis plan 
SAS
safety analysis set 
SIC
subject identification code
TGA
thrombin generation assays 
VIIa
activated factor VII 
WFH
World Federation of Hemophilia
For non-commercial use only

BAX 802
Page 17 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
The investigational product (IP), BAX 802, is a recombinant form of porcine factor VIII 
(rpFVIII) from which the B domain has been deleted. Deletion of the B domain does not 
affect the safety or efficacy of this recombinant form of human factor VIII (rhFVIII) in 
the treatment of hemophilia A. BAX 802 (rpFVIII) is being developed for the 
perioperative management of hemostasis in subjects with congenital hemophilia A 
(CHA) with inhibitors to human factor VIII (hFVIII) undergoing surgical or other 
invasive procedures. This rpFVIII was approved by the United States Food and Drug 
Administration (FDA) in 2014 for the treatment of bleeding episodes in adults with 
acquired hemophilia A (AHA; non hemophilia subjects developing spontaneous 
autoantibody inhibitors to hFVIII) under the trade name OBIZUR®.
6.2 Clinical Condition/Indication
Congenital hemophilia A is a congenital bleeding disorder caused by a deficiency or 
complete absence of coagulation factor VIII (FVIII)1 and is referred to as CHA in order 
to differentiate it from AHA, which is a rare autoimmune disease with different bleeding 
patterns caused by immunoglobulin G antibodies that bind to specific domains on the 
FVIII molecule, in a person with a negative personal or family history of a 
coagulopathy.2
Overall, CHA accounts for about 80% of hemophiliacs. It affects all ethnic populations 
and its prevalence varies among different countries, but is estimated at a rate of 3 to 
20 cases per 100,000 population. The World Federation of Hemophilia (WFH) has 
estimated the total number of hemophilia cases at about 500,000 universally, of which 
one-third are diagnosed. The tendency to bleed in these subjects correlates with the 
plasma level of FVIII. This lifelong disorder has 3 clinical phenotypes (severe, moderate, 
and mild) that correlate with FVIII levels in plasma (< 1%, 1 to 5%, and 5 to 30%, 
respectively).3
Subjects with hemophilia A typically develop recurrent bleeding episodes. The most 
effective approach for treatment of acute bleeding episodes in subjects with hemophilia A 
is hFVIII replacement therapy.4, 5 However, a major complication in the treatment of 
subjects with hemophilia A is the development of neutralizing antibodies (inhibitors) to 
hFVIII, which impair the efficacy of replacement therapy with hFVIII concentrates. 
Inhibitor development occurs more frequently among patients with severe or moderately 
severe hemophilia, and approximately 30% of patients with severe CHA develop 
For non-commercial use only

BAX 802
Page 18 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
inhibitors. In CHA patients with high-responding inhibitors, standard replacement 
therapy with FVIII concentrates is usually ineffective, resulting in poor control of 
hemorrhagic episodes. This in turn increases the risk of morbidity, mortality, orthopedic 
complications and disability, as well as reduced quality of life, compared with patients 
without inhibitors.6 Patients with CHA with inhibitors are also at risk of perioperative 
bleeding complications, since replacement of the missing coagulation factor is 
ineffective, presenting a therapeutic challenge in elective or emergency surgery.7
Currently Available Treatments and Unmet Medical Need
In CHA patients with transient, low-responding and/or low-titers (< 5 Bethesda units 
[BU]/mL) inhibitors, increased doses of FVIII may be sufficient to overcome the 
inhibitor and provide hemostasis. In CHA patients with high-responding inhibitors 
(> 5 BU/mL), standard replacement therapy with FVIII concentrates is usually 
ineffective, resulting in poor control of hemorrhagic episodes. 
Alternative therapies are required for subjects with inhibitors who no longer respond to 
hFVIII replacement therapy. Recombinant activated factor VII (rFVIIa, NovoSeven®) 
and FEIBA (FVIII inhibitor bypassing activity; anti-inhibitor coagulant complex [AICC]) 
bypass the normal coagulation cascade and hence the FVIII inhibitors, and are therefore 
referred to as bypassing agents. Although these agents are able to manage bleeding in the 
presence of inhibitors, they do not attempt to restore the normal pathways of hemostasis, 
but instead boost thrombin generation despite a lack of platelet-surface FVIIIa–FIXa 
(‘tenase’) activity.6 The measurement of levels of factor VIIa in the subject’s plasma 
cannot be used as a clinically relevant surrogate marker and does not correlate with 
clinical outcome. Without an adequate biomarker, the dosage and treatment schedule 
cannot be clearly defined.8 In addition, the response to rFVIIa treatment may be 
inconsistent both from subject to subject and between different bleeds in the same 
subject. Because FEIBA is a human plasma fraction containing several coagulation 
factors, it has the potential to transmit human pathogens and may also cause 
thromboembolic events. Since the plasma fraction also contains hFVIII, it has been
associated with a rise in hFVIII antibodies in approximately 20% of subjects.9
Moreover, as with rFVIIa, there is no validated biomarker that correlates with the clinical 
outcome with FEIBA treatment, although both thrombin generation assays (TGA) and 
whole blood viscoelastic assays have been evaluated for this purpose with some 
success.10
For non-commercial use only

BAX 802
Page 19 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The ultimate goal of treatment for these patients is eradication of the inhibitor through 
immune tolerance induction (ITI), which involves frequent and long-term administration 
of factor concentrates in an attempt to build tolerance in the immune system to FVIII or 
factor IX, and thus restore responsiveness to factor replacement therapy. However, 
ITI fails in approximately 30% of inhibitor patients with CHA.6
There is therefore a clinical need for an effective hemostatic agent for use in subjects 
with CHA who have inhibitors to hFVIII, and which allows monitoring of hemostatic 
efficacy based upon measurement of plasma FVIII activity levels, thus facilitating early 
determination of clinical benefit and the patient’s clinical status.
6.3 Population to be Studied
The study population will comprise of at least 10 surgeries in 10 evaluable male subjects 
with CHA with inhibitors to hFVIII undergoing major or minor elective surgical, dental, 
or other invasive procedures (at least 5 major surgeries in 5 evaluable subjects). Adult 
(≥18 and ≤65 years) male subjects will be considered to be eligible provided that they 
satisfy all of the inclusion criteria listed in Section 9.1 and none of the exclusion criteria 
listed in Section 9.2.
6.4 Findings from Nonclinical and Clinical Studies
6.4.1 Finding from Nonclinical Studies
Nonclinical studies were performed with rpFVIII to demonstrate hemostatic activity in 
2 animal models of hemophilia A (mice and dogs), local and systemic tolerance in a 
range of doses in single or repeat dose toxicology studies in monkeys, pharmacokinetics 
(PK) in dogs and monkeys, and immunogenicity in mice and monkeys.
Compatibility with the usual injection materials (needles, plastic syringes, and butterfly 
infusion needles with tubing) has been demonstrated. Studies in monkeys demonstrated 
the tolerability of repeated single daily injections of rpFVIII at doses up to 1000 U/kg, 
with injections at each dose level given once daily for 7 days. In 2 animal models of 
hemophilia A (mice and dogs), the hemostatic activity of rpFVIII was studied in 
comparison with Hyate:C. The rpFVIII was found to be efficacious in a dose-related 
fashion in controlling the bleeding associated with a standardized hemorrhagic insult. No 
animal studied was observed to have had an acute reaction to the injection of rpFVIII.
For non-commercial use only

BAX 802
Page 20 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.4.2 Findings from Clinical Studies
The safety and efficacy of rpFVIII was explored in 4 clinical trials prior to marketing 
approval:
OBI-1-101: a Phase I, multicenter, randomized, double-blinded, double-dummy, 
parallel-group, comparison of the safety, tolerance, and PK study of rpFVIII versus 
Hyate:C was conducted.11
OBI-1-201: a Phase II, prospective, open-label, non-comparative study was 
conducted to assess the hemostatic activity of rpFVIII. Eligible subjects had a 
clinical diagnosis of hemophilia A with inhibitors to hFVIII, an anti-pFVIII
inhibitor antibody titer < 20 BU at screening, and an uncomplicated joint or soft 
tissue bleed, or other non-life threatening and non-limb threatening bleeding 
episode.12
OBI-1-301: a multicenter, open-label, single-cohort, prospective, Phase II/III study 
of rpFVIII in subjects with acquired hemophilia to determine the hemostatic 
efficacy and safety of rpFVIII in the control of serious bleeding episodes.13
OBI-1-302: a prospective, non-randomized, open-label study designed to assess 
treatment of serious bleeding episodes with rpFVIII in subjects with CHA who had 
developed anti-hFVIII inhibitors; this study was terminated by the sponsor after 
1 subject was treated for administrative reasons, not due to safety or lack of 
efficacy concerns.
In all clinical studies, rpFVIII was generally well tolerated. There were no drug-related 
AEs reported in subjects who received rpFVIII in the Phase I study. One subject in the 
Phase II study (OBI-1-201) experienced pruritus (that resolved with diphenhydramine) 
that was possibly related to study drug. This AE occurred during the first bleeding 
episode, but the subject did not have a reaction during a second rpFVIII treated bleeding 
episode. In the Phase I and Phase II studies, no AEs led to treatment interruption, 
discontinuation from the study, or death. Vital signs, laboratory values, medical history 
and physical examination findings were within normal parameters for both studies and 
raised no safety concerns. 
In the Phase II study (OBI-1-201), the ITT Population consisted of 9 male subjects with 
CHA and with an inhibitor antibody to hFVIII. Six of the subjects (67%) were black and 
3 subjects (33%) were Caucasian. The mean age of the subject population was 23.7 years 
(Range: 14 to 34). The primary efficacy objective of the study was to evaluate the 
hemostatic efficacy of rpFVIII in the treatment of non-life/non-limb threatening bleeds in 
subjects with CHA and inhibitors.
For non-commercial use only

BAX 802
Page 21 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
A total of 25 bleeds in 9 subjects were treated with rpFVIII and all bleeds were 
successfully controlled with 8 or less injections of rpFVIII. The median number of 
rpFVIII injections administered per bleeding episode was 1.0 (Range: 1 to 8) and the 
median time from bleeding onset to treatment was 5.67 hours (range: 1.5 to 20.0 hours). 
Across all bleeding episodes the median total dose of rpFVIII per bleeding episode was 
224.1 U/kg (range: 50.0 to 1066.4 U/kg). The median initial Treatment Dose (including 
the Loading Dose if applicable), was 159 U/kg (Range: 50 to 576 U/kg) and resulted in a 
median increase of FVIII plasma level of 16 % with the 1-stage clotting assay (Range: 
0.5 to 427 %) and a median increase of 17% with the chromogenic assay (Range: 0 to 
248 %). Twenty of the 25 (80%) bleeds were controlled within 6 hours having been 
administered 1 Treatment Dose of rpFVIII. For those 20 bleeds controlled with 
1 Treatment Dose (including the Loading Dose if applicable), the median dose was 
200.8 U/kg. rpFVIII was well tolerated and of the reported AEs (n=61) only 18 were 
considered treatment emergent. Two subjects reported an AE that was possibly related to 
study drug. One AE of itching/pruritus during the first bleeding episode but without 
reaction during a second rpFVIII treated bleeding episode. The second AE was a report 
of increased ALT and AST, possibly associated with a confirmed Hepatitis C infection, 
while it was uncertain whether the corresponding blood sample was taken before or after 
rpFVIII administration. Three subjects suffered treatment emergent SAEs but none were 
considered related to study drug. No reported AE led to treatment interruption, 
discontinuation from the study or death. Eight out of 9 (8/9, 89%) subjects developed 
anti-pFVIII antibodies following exposure to rpFVIII. In subjects that received repeated 
rpFVIII treatment, higher anti-pFVIII titers did not affect efficacy or safety and no 
increase in AEs or bleeding episodes were reported in the subjects with the highest titers. 
Regardless of the observed anti-pFVIII titers at pre-treatment or the obtained FVIII 
recovery values after treatment initiation, all bleeding episodes were successfully 
controlled. Analyses of baby hamster kidney (BHK; host cell line) antibody levels 
indicated that no subjects produced detectable levels of antibodies against BHK.
In the prospective, open-label trial (OBI-1-301), the efficacy of rpFVIII for the 
treatment of serious bleeding episodes in subjects with AHA was investigated. The 
trial was conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects 
diagnosed with AHA, having auto-immune inhibitory antibodies to hFVIII, and 
experiencing serious bleeding episodes that required hospitalization. Subjects with a 
prior history of bleeding disorders other than AHA, anti-pFVIII antibody titer > 20 BU, 
or in whom the bleeding episode was judged likely to resolve on its own, were excluded. 
One subject was considered evaluable at study entry; however, it was later determined 
that this subject did not have AHA, leaving 28 subjects evaluable for efficacy. 
For non-commercial use only

BAX 802
Page 22 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Of the 28 subjects evaluable for efficacy, all subjects had a positive response to treatment 
for the initial bleeding episodes at 24 hours after dosing. A positive response was 
observed in 95% (19/20) of subjects evaluated at 8 hours and 100% (18/18) at 16 hours. 
In addition to response to treatment, the overall treatment success was determined by the 
investigator based on his/her ability to discontinue or reduce the dose and/or dosing 
frequency of rpFVIII. A total of 24/28 subjects (86%) had successful treatment of the 
initial bleeding episode. Of those subjects treated with rpFVIII as first-line therapy, 
defined as no immediate previous use of anti-hemorrhagic agents prior to the first 
rpFVIII treatment, 16/17 subjects (94%) had eventual treatment success reported. Eleven 
subjects were reported to have received anti-hemorrhagics (eg. rFVIIa, activated 
prothrombin-complex concentrate, tranexamic acid) prior to first treatment with rpFVIII. 
Of these 11 subjects, 8 had eventual successful treatment (73%). No related serious 
adverse reactions occurred. Non-serious adverse events related to treatment were noted 
and assessed by the investigator in 6/29 subjects (20.7%). One subject had mild 
tachycardia, hypotension and constipation. One subject had 2 instances of mild PICC line 
occlusion. One subject had a mild hypofibrogenemia and 1 subject had moderate mental 
status changes. All of these adverse effects completely resolved. Two subjects developed 
anti-porcine FVIII (pFVIII) inhibitors after infusion of study drug (range 8 to 51 BU) and 
were discontinued from treatment; however both subjects had a positive response to 
treatment at the 24 hour primary endpoint assessment. An investigation was conducted by 
the sponsor and, in summary, the 2 incidences of anti-pFVIII inhibitors were considered 
related to rpFVIII treatment, while the other non-serious treatment-related adverse events 
were considered as unlikely to be related to rpFVIII. Anti-pFVIII inhibitors were detected 
prior to infusion in 10/29 patients (range 0.8 to 29 BU). All of these subjects had a 
positive response at 24 hours post-rpFVIII first infusion. No anti-BHK antibodies were 
observed in any of the 29 treated subjects.
At the time of OBIZUR® marketing approval, the clinical trial data indicated that rpFVIII 
was well tolerated and had demonstrated effectiveness in the control of bleeding in study 
subjects. As of 2015 December 31, there have been 4 post-marketing spontaneous serious 
adverse event reports. The reports were considered possibly associated and consistent 
with the known safety profile of OBIZUR®.14
For non-commercial use only

BAX 802
Page 23 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Porcine FVIII (Hyate:C), derived from porcine plasma, had been used successfully 
starting in the 1980s to achieve hemostasis in the presence of anti-hFVIII inhibitors, as 
the antibodies generally have low immunological cross-reactivity with pFVIII.15
However, the number of hemophilia A subjects who were appropriate candidates to 
receive Hyate:C was limited by the degree to which their anti-hFVIII antibodies 
cross-reacted with pFVIII and the presence of any anti-pFVIII inhibitors. While a median 
inhibitor cross-reactivity observed to porcine VIIIC was only 15%, an absent, 
intermediate, or brisk specific anti-porcine anamnestic response was observed in 29%, 
40%, and 31% of patients, respectively.16 The commercial production of Hyate:C was 
discontinued in 2005 due to problems with sourcing suitable porcine plasma, but not due 
to any safety or efficacy concerns. 
BAX 802 is a B-domain deleted rpFVIII glycoprotein which is being developed for the 
perioperative management of hemostasis in subjects with CHA with FVIII inhibitors 
undergoing surgical or other invasive procedures. B-domain deleted rpFVIII glycoprotein 
has been extensively studied. BAX 802 (as marketed OBIZUR®) is not currently 
indicated for the treatment of CHA.17
OBIZUR® was approved based on the safety and efficacy data from 28 subjects with 
AHA treated with B-domain deleted rpFVIII glycoprotein in the Phase 2/3 open-label 
clinical study OBI-1-301. The safety, hemostatic activity, and PK profile of B-domain 
deleted rpFVIII glycoprotein was also supported by results of an open-label Phase 2 
study in patients with CHA with inhibitors (CSR OBI-1-201), and a randomized Phase 1 
study comparing B-domain deleted rpFVIII glycoprotein with a plasma-derived pFVIII 
(CSR OBI-1-101). 
The data supported the use of B-domain deleted rpFVIII glycoprotein to treat serious 
bleeding episodes in AHA patients (Section 6.4.2). It was demonstrated that B-domain 
deleted rpFVIII glycoprotein provides benefit to AHA patients who are unresponsive to 
alternative agents with an improved dosing algorithm. It was possible to monitor 
hemostatic efficacy based upon measurement of plasma FVIII activity levels, thus 
facilitating early determination of clinical benefit and the patient’s clinical status. An 
additional benefit to the patient was that it was possible to adjust the dose based on the 
FVIII levels rather than follow fixed dosing, ensuring that adequate doses were 
administered to achieve hemostasis.
For non-commercial use only

BAX 802
Page 24 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The most frequently reported adverse reaction in patients with AHA was the development 
of inhibitors to pFVIII.17
Overall, efficacy and safety clinical data for OBIZUR supported a favorable benefit/risk 
determination for the proposed indication of treatment of bleeding episodes in adults with 
AHA.
These data support the investigation of efficacy and safety of BAX 802 in subjects with 
CHA with inhibitors undergoing surgical or other invasive procedures. 
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council 
for Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), 
Title 21 of the US Code of Federal Regulations (US CFR), the EU Directives
2001/20/EC and 2005/28/EC, and applicable national and local regulatory requirements.
For non-commercial use only

BAX 802
Page 25 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to evaluate the efficacy and safety of BAX 802 in males with 
CHA with inhibitors who are undergoing major or minor elective surgical, dental, or 
other invasive procedures. 
7.2 Primary Objective
The primary objective of the study is to evaluate the perioperative hemostatic efficacy of 
BAX 802 in male subjects with CHA with inhibitors to hFVIII undergoing major or 
minor elective surgical, dental, or other invasive procedures as determined by the Global 
Hemostatic Efficacy Assessment (GHEA) score.
7.3 Secondary Objectives
The secondary objectives of the study are to:
1. To determine the safety of BAX 802 used in the perioperative setting by assessing:
The development of and change in titer of anti-pFVIII and anti-hFVIII inhibitory 
antibodies (binding and neutralizing), and development of binding antibodies to 
BHK proteins
The occurrence of thrombotic events and/or allergic reactions to BAX 802
The occurrence of AEs related to BAX 802
The occurrence of clinically significant changes in vital signs and routine 
laboratory parameters related to BAX 802
2. To determine the intra- and postoperative and overall perioperative blood loss at the 
end of surgery, compared to the estimated volume of expected average and 
maximum blood loss in a comparable healthy individual as predicted preoperatively 
by the investigator/surgeon
3. To determine the daily and total weight-adjusted administration of BAX 802 per 
subject
4. To determine the blood product utilization 
5. To determine the occurrence of bleeding episodes during the intra- and postoperative 
periods and additional need for surgical intervention
6. To evaluate any unrelated bleeding episodes in the postoperative period.
For non-commercial use only

BAX 802
Page 26 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8. STUDY DESIGN
8.1 Brief Summary
This study is a Phase 3, uncontrolled, open-label, single-group, multicenter study to 
determine the safety and efficacy of BAX 802 in at least 10 surgeries in 10 evaluable 
male subjects with CHA with inhibitors to hFVIII who are undergoing major or minor 
elective surgical, dental, or other invasive procedures (at least 5 major surgeries in 
5 evaluable subjects).
8.2 Overall Study Design
This study is a Phase 3, prospective, open-label, uncontrolled, multicenter study to 
evaluate the efficacy and safety of BAX 802 in at least 10 surgeries in 10 evaluable male 
subjects with CHA with inhibitors to hFVIII who are undergoing major and minor 
surgical, dental or other invasive procedures. At least 5 of the procedures must be major 
surgeries in 5 evaluable subjects (see Section 8.2.1).
The dose and frequency of BAX 802 during the preoperative, intraoperative, and 
postoperative periods should follow a substitution plan provided by the investigator prior 
to surgery and adjusted based on regular FVIII activity measurements. The regimen will 
depend on the type of surgery performed and the intensity of the hemostatic challenge.
Elective surgical procedures will prospectively be defined as major or minor by the 
investigator/surgeon and agreed with the medical director/designee, based on the protocol 
guidance and definitions and in consideration of each subject’s characteristics. 
Emergency surgeries are not in the scope of this study. Subjects may undergo more than 
1 surgery or 2 parallel surgeries, such as bilateral knee replacement. For subjects 
undergoing multiple surgeries (other than parallel surgeries), the End of Study visit
should be completed for the first surgery and then subject needs to be re-screened
(Section 10.3) for the next surgery.
The study will be conducted globally and will be divided into 5 periods: Screening, 
Preoperative, Intraoperative, Postoperative, and End of study (Table 8).
The overall study design is illustrated in Figure 1. 
8.2.1 Types of Interventions
Elective procedures will prospectively be defined by the investigator/surgeon as major or 
minor based on the definitions and examples provided in Section 8.2.1.1 and 
Section 8.2.1.2 taking into consideration each individual patient’s characteristics and 
agreement with the sponsor. 
For non-commercial use only

BAX 802
Page 27 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.2.1.1 Major Surgeries
Major surgeries include surgeries that require moderate or deep sedation, general 
anesthesia, or major conduction blockade for patient comfort. This generally refers to 
major orthopedic (eg, joint replacement), major abdominal, intracranial, cardiovascular, 
spinal and any other surgery which has a significant risk of large volume blood loss 
(> 500 mL) or blood loss into a confined anatomical space. Several tooth extractions or 
extraction of the third molar are generally considered as major. Examples include:

bone fixation for fracture

hip and knee replacement (arthroplasty)

arthrodesis (joint fusion)

open synovectomy

osteotomy

liver biopsy

pseudotumor removal

hardware removal (plates, intramedullary nails)
Major surgeries/interventions are expected to require clinical surveillance or hospital 
treatment > 3 days after the surgery/intervention. 
8.2.1.2 Minor Surgeries
Minor surgeries include surgeries that can be safely and comfortably performed on a 
patient who has received local or topical anesthesia, without more than minimal 
preoperative medication or minimal preoperative medication or minimal intraoperative 
sedation. The estimated total blood loss should be < 500 mL and the likelihood of 
complications requiring hospitalization or prolonged hospitalization should be remote. It 
refers to interventions such as removal of skin lesions, arthroscopy, minor dental 
procedures or dental extractions. Examples include:

removal of skin lesions

minor dental procedures or dental extractions (except extraction of several teeth or 
third molar extraction)

placement and/or removal of central venous catheters

synoviorthesis and arthrocentesis
For non-commercial use only

BAX 802
Page 28 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

arthroscopy

nerve release

removal of osteophytes and small cysts 
Minor surgeries/interventions are expected to require clinical surveillance or hospital 
treatment ≤3 days after the surgery/intervention
8.2.2 Dose Selection Rationale
Background
This is a Phase 3, open label study of the efficacy and safety of B-domain deleted rpFVIII 
(BAX 802) in the perioperative management of hemostasis in subjects with CHA who 
have inhibitors and are undergoing surgical or other invasive procedures. The rpFVIII 
temporarily replaces the inhibited FVIII that is needed for effective hemostasis in CHA 
patients who have developed inhibitors to hFVIII. The principle of using pFVIII is based 
on its low cross-reactivity with anti-hFVIII antibodies due to sequence variations 
between human and pFVIII in the A2 and C2 domains, the main targets of FVIII 
inhibitors. The rpFVIII concentrate is predicted to have an advantage over human-derived 
FVIII in CHA patients who have inhibitors since previous studies demonstrated that the 
antibodies have a median of only 15% cross-reactivity with plasma-derived pFVIII.18
Regulatory approval for rpFVIII for the treatment of bleeding episodes in adults with 
AHA was received for OBIZUR®; per the product label, the initial dose of OBIZUR® is 
200 U/kg, with subsequent dosing dependent on the location and severity of bleeding 
episode, target FVIII levels, and the patient’s clinical condition.17
Influence of Anti-pFVIII Inhibitor Titer on the Loading Dose
Anti-pFVIII inhibitors are neutralizing antibodies against pFVIII that neutralize the 
pFVIII, and thereby reduce its hemostasis effect. Anti-pFVIII inhibitors can be quantified 
in plasma by the Bethesda assay, which measures the ability of the patient’s plasma to 
neutralize exogenous pFVIII when incubated together.  
The amount of BAX 802 required to neutralize the anti-pFVIII activity is factored in. A 
BU is defined as the amount of anti-pFVIII inhibitor in a plasma sample which will 
neutralize 50% of 1 unit of BAX 802 in normal plasma after 2 hour incubation at 37°C. 
For non-commercial use only

BAX 802
Page 29 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Only the inhibitor that is distributed in the plasma volume (PV) is initially available to 
neutralize the infused FVIII; PV is calculated using the following formula: 
PV = Blood Volume x (1 – [hematocrit{Hct}%/100])
Normal blood volume is approximately 80 mL/kg for adults.
Therefore, PV = 80 x (1 – [Hct%/100]).
One BU of anti-pFVIII inhibitor will neutralize 50% of 1 unit of BAX 802; therefore, it is 
assumed that 0.5 U FVIII will be required for each 1 BU of inhibitor. The amount of 
BAX 802 required to neutralize the anti-pFVIII activity can be estimated using the 
following:
Body weight x 80(1 - [Hct%/100]) x 0.5 x anti-pFVIII inhibitor titer (BU) = 
body weight x 40(1-[Hct%/100]) x anti-pFVIII inhibitor titer (BU).
Proposed Dosing Regimen of BAX 802 in Study BAX 802 Surgery
This regimen for loading dose of BAX 802 proposed for Study BAX 802 Surgery takes 
into account the titer of anti-pFVIII inhibitors. The dosing scheme to be used in 
Study BAX 802 Surgery is presented in Section 8.7.3.3.
The loading dose of BAX 802 for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
80 U/kg + body weight x 40(1-[Hct%/100]) x anti-pFVIII inhibitor titer (BU)
For example, for a 70 kg subject undergoing major surgery and having hematocrit 45% 
and anti-pFVIII inhibitor titer 3 BU, the loading dose of BAX 802 will is calculated as 
follows: 
80 (70) + 70 x 40(1-[45/100]) x 3 = 10,220 U
This dosing scheme should reasonably predict the loading dose before surgery that will 
provide sufficient FVIII levels needed for effective hemostasis.
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved (Table 5).
This dosing algorithm is essentially equivalent to that proposed by Kasper (2004) when 
using FVIII in the treatment of patients with low titer inhibitors.19
For non-commercial use only

BAX 802
Page 30 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study will be approximately 20 months from study initiation 
(ie, first subject enrolled) to study completion (ie, last subject, last visit). The recruitment 
period is expected to be 13 to 16 months.  
The duration of subject participation depends on the nature of the invasive procedure: it 
will run from the signing of the informed consent until completion of the End of Study 
Visit up to 6 weeks post-surgery (surgery = Day 0), unless prematurely discontinued. 
Study completion is defined by the End of Study Visit after discharge.
8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is the GHEA score (Table 1), which is composed of 
3 individual ratings:
Assessment of intraoperative hemostatic efficacy of BAX 802 performed by the 
operating surgeon (see Table 2)
Assessment of postoperative hemostatic efficacy of BAX 802 at postoperative 
Day 1 (approximately 24 hours after surgery) performed by the operating surgeon 
(see Table 3)
Assessment of overall perioperative hemostatic efficacy of BAX 802 at Day 14 or 
discharge (whichever is earlier), performed by the investigator (see Table 4)
The scores of each of the 3 individual ratings described above, will be added together to 
form a GHEA score according to Table 1. For a GHEA score of 7 to be rated “excellent” 
no individual assessment score should be less than 2 (ie, one individual assessment score 
must be 3 and the other 2 individual assessment scores must be 2). The only other option 
to achieve a GHEA score of 7 is for 2 individual assessment scores of 3 and one 
individual assessment score of 1. Although this GHEA score will not qualify for a rating 
of “excellent,” the GHEA score will satisfy the definition of “good,” (with no individual 
assessment score less than 1). All possible combinations of the individual assessment 
scores and their related ratings are provided in Supplement Section 20.5. Missing scores 
will be counted as 0.
The assessment of primary outcome measure (GHEA score) should only account for the 
blood loss related to the surgery and exclude any blood loss which is considered as 
unrelated bleeding (defined as any bleeding occurring at a different anatomical site than 
the surgery site during the postoperative period, see Section 11.2.5).
For non-commercial use only

BAX 802
Page 31 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 1: Global Hemostatic Efficacy Assessment (GHEA)
Assessment
GHEA Score
Excellent
7a to 9
(with no category scored < 2)
Good
5 to 7a
(with no category scored < 1)
Fair
3 to 4
(with no category scored < 1)
None
0 to 2 (or at least one category scored 0)
a
For a GHEA score of 7 to be rated “excellent” (with no individual assessment scores less than 2), at 
least 1 individual assessment score must be 3 and the other 2 individual assessment scores must be at 
least 2; otherwise a score of 7 is rated “good”.
Table 2: Intraoperative Efficacy Assessment Scale
A
At the time of discharge from the OR, the operating surgeon will assess the 
intraoperative hemostatic efficacy
Rating
Criteria
Score
Excellent
Intraoperative blood loss was less than or equal to that expected for the type 
of procedure performed in a non-hemophilic population (≤100%)
3
Good
Intraoperative blood loss was up to 50% more than expected for the type of 
procedure performed in a non-hemophilic population (101 to 150%)
2
Fair
Intraoperative blood loss was more than 50% of that expected for the type 
of procedure performed in a non-hemophilic population (> 150%)
1
None
Uncontrolled hemorrhage that was the result of inadequate therapeutic 
response despite proper dosing, necessitating rescue therapy 
0
Table 3: Postoperative Efficacy Assessment Scale (Postoperative Day 1)
B
On postoperative Day 1, the operating surgeon will assess the postoperative hemostatic 
efficacy by the operating surgeon
Rating
Criteria
Score
Excellent
Postoperative blood loss was less than or equal to (≤100%) that expected 
for the type of procedure performed in a non-hemophilic population
3
Good
Postoperative blood loss was up to 50% more (101% to 150%) than 
expected for the type of procedure performed in a non-hemophilic 
population 
2
Fair
Postoperative blood loss was more than 50% (> 150%) of that expected for 
the type of procedure performed in a non-hemophilic population 
1
None
Significant postoperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy 
0
For non-commercial use only

BAX 802
Page 32 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 4: Overall Perioperative Efficacy Assessment Scale (Day 14)
C
At Day 14 or discharge (whichever is earlier), a hematologist will assess the 
postoperative efficacy
Rating
Criteria
Score
Excellent
Overall perioperative blood loss was less than or equal to (≤100%) that 
expected for the type of procedure performed in a non-hemophilic 
population,
Required blood components for transfusions were less than or similar to 
that expected in non-hemophilic population
3
Good
Overall perioperative blood loss was up to 50% more (101% to 150%) than 
expected for the type of procedure performed in a non-hemophilic 
population
Required blood components for transfusions were less than or similar to 
that expected in non-hemophilic population
2
Fair
Overall perioperative blood loss was more than 50% of that expected for the 
type of procedure performed in a non-hemophilic population (> 150%)
Required blood components transfusions were greater than that expected in 
non-hemophilic population
1
None
Significant overall perioperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy 
Required blood components for transfusions were substantially greater than 
that expected in non-hemophilic population
0
8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy
1.
Blood loss compared to the estimated volume of expected average blood loss and 
expected maximum blood loss in a comparable healthy individual as predicted 
preoperatively by the investigator/surgeon at the following time points:
Intraoperative, at the end of surgery
Postoperative Day 1, approximately 24 hours after surgery
Overall perioperative Day 14 or discharge (whichever is earlier)
2.
Daily and total weight-adjusted administration of BAX 802 per subject
3.
Volume of blood, red blood cells, platelets, and other blood products transfused
4.
Occurrence of bleeding episodes during the intra- and postoperative periods and 
additional need for surgical intervention
5.
Efficacy of the treatment of unrelated bleeding episodes in the postoperative 
period.
For non-commercial use only

BAX 802
Page 33 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2.2 Safety
1.
Development of, and changes to, the titer of inhibitory and binding antibodies to 
rpFVIII
2.
Development of, and changes to, the titer of inhibitory and binding antibodies to 
hFVIII
3.
Development of binding antibodies to BHK proteins
4.
Occurrence of thrombotic events
5.
Incidence of severe allergic reactions (eg, anaphylaxis)
6.
Incidence of other IP-related AEs
7.
Incidence of clinically significant changes in vital signs and routine laboratory 
parameters (hematology, clinical chemistry)
8.5 Randomization and Blinding
This is a non-randomized, open-label, active treatment clinical study.
8.6 Study Stopping Rules
The study will be halted (enrollment stopped), pending further review by the internal 
Safety Monitoring Committee (ISMC) and sponsor, if 1 or more of the following criteria 
are met:
1.
Two or more subjects develop a severe anaphylactoid reaction or any other 
serious adverse event (SAE) related to BAX 802 that would not be expected with 
a currently licensed rpFVIII product (OBIZUR®)
2.
Other AEs that are deemed to pose unacceptable risks to subjects.
The study may be terminated, if 1 or more of the following criteria are met:
1.
The sponsor decides to terminate the study based upon ISMC recommendation or 
its own assessment of safety
2.
The sponsor decides to terminate the study at any time for administrative reasons.
8.7 Investigational Product(s)
BAX 802 will be supplied as white lyophilized powder in 3 mL glass vials containing 
nominally 500 units per vial for reconstitution with 1.0 mL sterile water for injection. 
For non-commercial use only

BAX 802
Page 34 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.1 Packaging, Labeling, and Storage
BAX 802 will be supplied in a lyophilized form. For specific instructions for 
reconstitution, please refer to the Study Manual. A sufficient quantity of BAX 802 will be 
supplied to each study site, as well as an acknowledgement of receipt form.
The core label texts for all packaging units will be translated or adjusted, to be in 
compliance with applicable regulatory requirements, national laws in force and in 
accordance with the local languages. Minimally each vial will bear a label with the 
following information:
Sponsor name
Study number
Pharmaceutical dosage form
Route of administration
Name of IMP and actual quantity of dose units
Batch number
Space on which to record the subject number
The statement ‘For clinical trial use only’ or ‘Caution: new drug limited by Federal 
Law to investigational use’ or ‘To be used only by a qualified investigator’, as 
appropriate
Name, address and telephone number of the Sponsor, Contract Research 
Organization (CRO) or investigator, if appropriate
Storage conditions
Expiry or manufacturing date, as appropriate
The investigator or designee will only dispense BAX 802 to subjects included in this 
study.
8.7.2 Reconstitution and Administration
The reconstitution procedures for BAX 802 are detailed in the Pharmacy Manual. 
Reconstituted BAX 802 should be kept and administered at room temperature and must 
be administered within 3 hours of reconstitution.
BAX 802 will be administered as an intravenous infusion per the dosing schema for 
major and minor surgeries (Table 5).
For non-commercial use only

BAX 802
Page 35 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3 Description of Treatment
8.7.3.1 FVIII Maintenance Plan
Based on the category (minor or major) and type of surgery, the investigator must outline 
the expected FVIII maintenance plan with target peak and trough levels covering the 
surgical, dental or invasive procedure until expected wound healing. The FVIII 
maintenance plan will be provided to the medical director/designee to ensure that the 
recommendations regarding FVIII target levels as provided in the protocol are followed. 
Each FVIII maintenance plan for major surgeries requires prior approval of the medical 
director. The FVIII levels measured intra/postoperatively will be compared with the 
FVIII maintenance plan. Slight deviations from the predefined substitution plan are 
allowed based on investigators clinical judgment and available laboratory FVIII data.
It is recommended that the turnaround time for FVIII activity results from the local 
laboratories are ≤2 hours so that dosing decisions could be made and subjects are dosed 
adequately.
8.7.3.2 Perioperative Dosing
Adjustments to the dose and frequency of BAX 802 dosing during the intra- and 
postoperative period should follow the maintenance plan provided by the investigator 
prior to surgery. Adjustments must be based on regular FVIII activity measurements 
determined at pre- and post-dosing of BAX 802 and will depend on the type of the 
surgery performed and the intensity of the hemostatic challenge.
8.7.3.3 Dosing Schedule and Requirements
8.7.3.3.1 General
As described in Section 8.2.2, the loading dose will be calculated according to the 
following formula:
Loading Dose of BAX 802:
Major Surgery: 80 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII 
inhibitor titer (BU), administered approximately 1 to 2 hours prior to the surgery
Minor Surgery: 50 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII 
inhibitor titer (BU), administered approximately 1 to 2 hours prior to the surgery
The loading dose of BAX 802 for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
80 U/kg + body weight (kg) x 40(1-[Hct%/100]) x anti-pFVIII inhibitor titer (BU)
For non-commercial use only

BAX 802
Page 36 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For example, for a 70 kg subject undergoing major surgery and having hematocrit 45% 
and anti-pFVIII inhibitor titer 3 BU, the loading dose of BAX 802 will be calculated as 
follows: 
80 (70) + 70 x 40(1-[45/100]) x 3 = 10,220 U
Subsequent doses, dosing frequency, and duration of treatment will be based on the 
clinical judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved based on the following calculation (Table 5):
Required dose (U) = 
[body weight (kg) x desired FVIII rise (U/dL or % of normal)]/1.2 (U/kg per U/dL).
Table 5: Dosing for Perioperative Management
Type of 
Surgery
Recommended FVIII Level
(% of normal or U/dL)
Loading Dose
Subsequent Dose
Major
(see 
Section 8.2.1.1)
Prior to surgery: ≥80%
Postoperative up to 72 hours 
(if not yet discharged): ≥80%
Postoperative Day 4 – Day 7
(if not yet discharged): ≥50% 
(if not yet discharged)
Postoperative Day 8 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels do not fall 
below 30% (left to the 
discretion of the investigator 
depending on the postoperative 
course)
80 U/kg + body weight 
(kg) x 40(1-[Hct%/100]) x 
anti-pFVIII inhibitor titer 
(BU)1, administered 
approximately 1 to 2 hours
prior to the surgery
Titrate subsequent 
doses to maintain 
recommended FVIII 
trough levels and 
individual clinical 
response using 
following formula:
Required dose (U) 
= [body weight (kg) x 
desired FVIII rise 
(U/dL or % of 
normal)]/1.2 (U/kg 
per U/dL)
Minor 
(see 
Section 8.2.1.2)
Prior to surgery: ≥50%
Postoperative up to 72 hours 
(if not yet discharged): ≥50%
Postoperative Day 4 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels do not fall 
below 30% (left to the 
discretion of the investigator 
depending on the postoperative 
course)
50 U/kg + body weight 
(kg) x 40(1-[Hct%/100]) x 
anti-pFVIII inhibitor titer 
(BU)1, administered 
approximately 1 to 2 hours
prior to the surgery
1 Anti-pFVIII inhibitor titer and hematocrit information available from screening lab result will be used.
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
For non-commercial use only

BAX 802
Page 37 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If at any time during the study, a subject does not respond to BAX 802 therapy as 
anticipated either by the operating surgeon or hemophilia physician providing 
postoperative care, blood samples will be drawn for the determination of FVIII activity 
levels. In the event of unexplained, excessive bleeding, the subject will be treated by 
whatever means necessary until adequate hemostasis is achieved. If other rescue 
medications become necessary, the subject will subsequently be withdrawn from this 
BAX 802 surgery study. Adverse events and the details of concomitant medication and
blood product use coincident with the treatment of all unanticipated bleeding will be 
recorded. The use of adjunct antifibrinolytic therapy (such as tranexamic acid) is allowed 
if clinically indicated by the investigator and/or according to the standard of care of the 
subject’s institution.
8.7.3.3.2 Preoperative and Loading Dose
The subject will receive a loading dose calculated according to the formula described 
above in order to maintain a minimum target FVIII level as required by the category and 
type of surgery. The recommended loading dose will be calculated by the investigator. 
The initial loading dose will be administered within 60 to 120 minutes prior to surgery 
(prior to incision/intubation). 
In case of major surgery, FVIII target level is ≥80% for major surgeries/procedures and 
≥50% for minor surgeries/procedures.
It is recommended that the surgery starts after FVIII levels have achieved target 
levels. If FVIII activity post loading dose is close to the target level, a supplement 
dose of BAX 802 should be administered without further delaying the surgery. If 
FVIII activity post loading dose is not close to the target level, a supplement dose of 
BAX 802 should be administered and surgery delayed until FVIII levels have 
achieved target levels or are in close range.
ALL subsequent dosing of BAX 802 should be preceded by measurement of residual 
FVIII levels and dose adjustments must be based on the most recent residual FVIII 
activity levels. 
Note: It is recommended that the plasma levels of FVIII do not exceed 200%.
Note: Dose adjustments should not be based on activated partial thromboplastin 
time (aPTT) values.
For non-commercial use only

BAX 802
Page 38 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3.3.3 Postoperative Dosing
Major Surgery
After the initial loading dose, an optional re-dosing sufficient to raise FVIII levels to the 
appropriate level as defined for the type of surgery may be administered after a blood 
sample for FVIII determination has been drawn and the required FVIII levels by the local 
laboratory have been determined. 
Note:

FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as necessary. 

FVIII activity level should also be determined within 4 to 6 hours following 
major surgery, with dose adjustments as necessary. 

Following this, FVIII activity level should be determined at least every 
12 hours till 48 hours postoperative period (if not discharged yet), with dose 
adjustments as necessary.

Beginning on postoperative Day 3 (through discharge), subjects will have 
FVIII level measurement at least once per day in order to assess the 
adequacy of BAX 802 therapy during the postoperative period. For 
consistency, it is recommended that the daily blood draws are performed at 
the same time of the day, such as morning blood draws.
More frequent monitoring of FVIII activity is advised in subjects who have baseline 
anti-pFVIII inhibitor titers of >5 BU.
ALL subsequent dosing of BAX 802 must be preceded by measurement of residual 
FVIII levels pre-dose and FVIII level measurement 30 ±5 minutes post-dosing. 
It is recommended that the FVIII trough levels are within the range targeted for major 
surgery as per Table 5. Dosing adjustments based on aPTT values are not allowed.
Any modifications of the FVIII maintenance recommendations and the substitution plan 
that are deemed necessary during the postoperative period will be at the discretion of the 
investigator and will be documented on the eCRFs. 
At a minimum, a blood sample for FVIII determination must be drawn prior to any 
supplemental unscheduled FVIII infusion and 30 ±5 minutes post-dosing.
For non-commercial use only

BAX 802
Page 39 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Minor Surgery
After the initial loading dose, an optional re-dosing sufficient to raise FVIII levels to the 
appropriate level as defined for the type of surgery may be administered after a blood 
sample for FVIII determination has been drawn and the required FVIII levels by the local 
laboratory have been determined. 
Note:

FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as necessary. 

FVIII activity level should also be determined within 4 to 6 hours following 
minor surgery, with dose adjustments as necessary on the day of surgery. 

Following this, FVIII activity level should be determined at least every 
12 hours till 48 hours postoperative period (if not discharged yet), with dose 
adjustments as necessary.

In case the subject is hospitalized for more than 24 hours, daily pre- and 
post-infusion FVIII level determinations as described for major surgery have 
to be performed and the dose adjusted according to the residual FVIII levels.
More frequent monitoring of FVIII activity is advised in subjects who have baseline 
anti-pFVIII inhibitor titers of > 5 BU.
ALL subsequent dosing of BAX 802 must be preceded by measurement of residual 
FVIII levels and the dose adjusted as needed. Dosing adjustments based on aPTT 
values are not allowed.
It is recommended that the FVIII trough levels are within the range targeted for minor 
surgery as per Table 5. 
Any modifications of the FVIII maintenance recommendations and the substitution plan 
that are deemed necessary during the postoperative period will be at the discretion of the 
investigator and will be documented on the eCRFs. 
For non-commercial use only

BAX 802
Page 40 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3.3.4 Dosing for Unrelated Bleeding Episodes During the Postoperative Period
Unrelated bleeding episode is defined in Section 11.2.5. 
The BAX 802 dosing regimen for treatment of these bleeding episodes will be based on 
the guidelines in Table 6. These guidelines may be adjusted by the investigator based 
upon his or her clinical judgment.
It is critical that treatment of a bleed is initiated as soon as possible after occurrence 
of the bleeding episode.
Repeat infusions of BAX 802 can be administered to treat these bleeding episodes, as per 
investigator’s discretion.
When bleeding is controlled, additional infusions of BAX 802 to maintain hemostasis are 
permitted, if required. Infusions given to treat and control the unrelated bleeding episode
should be documented in the eCRF.
For a detailed description of bleeding episodes into different sites see Supplement 20.6. 
For non-commercial use only

BAX 802
Page 41 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 6: BAX 802 Treatment Guidelines for Unrelated Bleeding Episodes
Type of Bleeding Episode
Recommended 
FVIII Level (%)
BAX 802 Dose
Minor
Early hemarthrosis, mild muscle bleeding, 
or mild oral bleeding, including, epistaxis
20% to 40%
Required dose (U) = [body 
weight (kg) x desired FVIII rise1
(U/dL or % of normal)]/1.2 (U/kg 
per U/dL)
Titrate subsequent doses to 
maintain recommended FVIII 
trough levels and individual 
clinical response until the 
bleeding resolves.
Moderate
Moderate bleeding into muscles, bleeding 
into the oral cavity, definite hemarthrosis, 
and known trauma
30% to 60%
Major
Significant gastrointestinal bleeding, 
intracranial, intra-abdominal, or 
intrathoracic bleeding, central nervous 
system bleeding, bleeding in the 
retropharyngeal or retroperitoneal spaces or 
iliopsoas sheath, fractures, head trauma
60% to 100%
1 If the most recent residual FVIII activity level is from the measurement performed ≤4 hours of the 
bleeding episode, use this value to calculate desired FVIII rise. If the most recent residual FVIII activity 
level is from the measurement performed > 4 hours of the bleeding episode, the desired FVIII rise should 
be equivalent to the recommended FVIII level for that type of bleeding episode (as described in the 
column to the left).
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics
Commercially available gelatin sponges, topical thrombin, fibrin sealants, absorbable 
collagen preparations or anti-fibrinolytics (eg, tranexamic acid, ɛ-amino caproic acid) 
may be used according to each institution’s standard of care. Details, including the dose, 
of all adjunctive hemostatic medication used will be recorded in the eCRFs designed for 
this study and the reason for use given. 
Thrombosis prophylaxis can be administered at the discretion of the investigator 
according to the standard of care of each institution and recorded into the respective 
eCRF. Thrombosis prophylaxis should preferably consist of mechanical measures such as 
intermittent pneumatic compression (IPC), compression stockings and early mobilization. 
Pharmacologic thrombosis prophylaxis such as low molecular weight heparin (LMWH) 
may be considered for certain surgical interventions such as major orthopedic surgery 
after careful evaluation by the investigator of the potential risks and benefits.
For non-commercial use only

BAX 802
Page 42 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.5 Investigational Product Accountability
The investigator will ensure that the IP(s) is stored as specified in the protocol and that 
the storage area is secured, with access limited to authorized study personnel. The 
investigator will maintain records that the IP(s) was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received and 
disposition. IP(s) must be dispensed only at the study site or other suitable location (eg, 
infusion center; home, as applicable per study design). Records will be maintained that 
includes the subject identification code (SIC), dispensation date, and amount dispensed. 
All remaining partially used and/or unused IP(s) will be returned to the sponsor or 
sponsor’s representative after study completion/termination, or destroyed with the 
permission of the sponsor in accordance with applicable laws and study site procedures.
If IP(s) is to be destroyed, the investigator will provide documentation in accordance with 
sponsor’s specifications.
8.8 Source Data
Per ICH GCP, source data are defined as all information in original records and certified 
copies of original records of clinical findings, observations, or other activities in a clinical 
trial that are necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents (original records or certified copies), which may be in 
paper and/or electronic format. Source data for this study comprise the following: 
hospital records, medical records, clinical and office charts, laboratory notes, memoranda, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical study.
No data will be entered directly onto the case report form (CRF).
For additional information on study documentation and CRFs, see Section 17.2.
For non-commercial use only

BAX 802
Page 43 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subject is ≥ 18 to ≤ 65 years old at the time of screening
2.
Subject has provided signed informed consent
3.
Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤2%) 
CHA with inhibitors to human FVIII, as tested at screening at the central 
laboratory
4.
Subject requires elective surgery or other invasive procedures
5.
Subject is not currently receiving or has received (< 30 days) ITI therapy
6.
Subject has a Karnofsky performance score of ≥60
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable 
disease and CD4+ count ≥200 cells/mm3 at screening
8.
Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain 
reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease
9.
Subject is willing and able to comply with the requirements of the protocol.
9.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
The subject requires emergency surgery
2.
The subject’s weight is < 35 kg or > 120 kg
3.
Clinically symptomatic liver disease (eg, ≥5 X upper limit of normal alanine 
aminotransferase [ALT], as confirmed by central laboratory at screening, clinical 
evidence of portal hypertension, severe hypoalbuminemia or a documented 
prothrombin time/international normalized ratio (PT/INR) > 1.5)
4.
Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as 
confirmed by central laboratory at screening
5.
Anti-porcine inhibitor > 10 BU prior to surgery
6.
Platelet count < 100,000/µL
7.
Subject has another active coagulation disorder other than hemophilia A, as per 
the medical history
For non-commercial use only

BAX 802
Page 44 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.
Planned use of α-interferon with or without ribavarin 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
9.
Known hypersensitivity to rpFVIII, or hamster or murine proteins
10. Subject has been exposed to an IP within 30 days prior to enrollment or is 
scheduled to participate in another clinical study involving an IP or 
investigational device during the course of this study
11. Unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the investigator. 
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw (ie, reduce the degree of participation in the study) 
consent for continued participation and data collection. The reason for withdrawal will be 
recorded on the End of Study CRF. Assessments to be performed at the termination visit 
(including in cases of withdraw or discontinuation) are described in Section 10.7, 
Section 20.3, and Section 20.4.
Discontinuation (ie, complete withdrawal from study participation) may be due to 
dropout (ie, active discontinuation by subject) or loss to follow-up (ie, discontinuation by 
subject without notice or action). Additionally, the investigator and sponsor have the 
discretion to discontinue any subject from the study if, in their judgment, continued 
participation would pose an unacceptable risk for the subject.
Subjects also will be withdrawn from treatment or discontinued from further study 
participation for the following reasons:
AEs/SAEs that in the investigator or sponsor opinion, poses an unacceptable risk 
for continued dosing in the subject
The subject is determined by the sponsor or investigator to be noncompliant with 
administration of IP, despite evidence of retraining of the subject. The subject will 
be discontinued from further participation in the study
Participation in another clinical study involving an IP during the course of the study
The subject experiences a severe anaphylactic reaction
The subject had uncontrolled hemorrhage that was the result of inadequate 
therapeutic response despite proper dosing of rpFVIII, necessitating rescue therapy 
with bypassing agents.
For non-commercial use only

BAX 802
Page 45 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10. STUDY PROCEDURES
10.1 Informed Consent
Any patient who provides informed consent (ie, signs and dates the informed consent 
form and assent form, if applicable) is considered a subject in the study.
10.2 Subject Identification Code
The following series of numbers will comprise the SIC: protocol identifier (241502) to be 
provided by the sponsor, 2-digit number study site number (eg, 02) to be provided by the 
sponsor, and 3-digit subject number (eg, 003) reflecting the order of providing informed 
consent. For example, the third subject who signed an informed consent form at study site 
02 will be identified as Subject 241502-02003. All study documents (eg, CRFs, clinical 
documentation, sample containers, drug accountability logs, etc.) will be identified with 
the SIC. Additionally, a uniquely coded SIC(s) is permitted as long as it does not contain 
a combination of information that allows identification of a subject (eg, collection of a 
subject’s initials and birth date would not be permitted), in compliance with laws 
governing data privacy.
10.3 Screening and Study Visits
The study site is responsible for maintaining a screening log that includes all subjects 
who provided informed consent. The log also will serve to document the reason for 
screening failure.
All screening data will be collected and reported in CRFs, regardless of screening 
outcome. If a subject is re-screened, the End of Study CRF should be completed, and a 
new informed consent form (ICF), new SIC and new CRF are required for that subject. 
Subjects who fail screening due to a single laboratory test result that does not meet 
eligibility criteria may have that laboratory test repeated at the discretion of the 
investigator. This will include a repeat of only the failed assessment; complete re-
screening will not be necessary. In these cases, a new SIC is not required; the subject will 
maintain their original SIC. The repeat of a screening assessment is allowed once. A 
repeat assessment must take place within 42 days of the initial screening for any subject 
requiring repeat of a screening assessment. If this timeframe is exceeded, then all 
screening assessments must be repeated and the subject assigned a new SIC. Exemptions 
are possible for administrative reasons and have to be approved by the sponsor. Subjects 
with an inadequate interval between screening and prior IP drug (other than BAX 802) 
administration or prior participation in a drug or device study (ie, 30 days), may be 
re-screened only once and only when the required interval is reached. 
For non-commercial use only

BAX 802
Page 46 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The screening assessment should be performed within 45 days prior to the planned 
elective surgery.
The overall study design is illustrated in Supplement Figure 1. Details on the procedures 
to be performed at each study visit, including screening, can be found in Supplement 20.3
and Supplement 20.4.
10.4 Study Periods
The study will be divided into 5 periods: 
1.
Screening
2.
Preoperative 
3.
Intraoperative
4.
Postoperative
5.
End of study 
A detailed description of study procedures per study period is provided in 
Supplement 20.1.
10.4.1 Discharge/End of Study Visit
Discharge Visit will be performed when the subject is discharged and the End of Study 
Visit will be performed 42 to 49 days following the completion of the surgical procedure. 
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the 
End of Study visit, the respective visits will be done as a single visit.
10.4.2 Optional Antibody Testing Visit
Whenever feasible, a visit will be performed between 7 to 14 days after the subject is 
discharged. Study procedures will be performed as per Table 9 and blood samples will be 
collected for antibody testings and other tests as per Table 10. This visit is optional.
For non-commercial use only

BAX 802
Page 47 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.5 Medications and Non-Drug Therapies 
The following medications are not permitted:
Medications:

Hemophilia inhibitor bypassing therapy (recombinant factor VIIa [NovoSeven] 
within 3 hours or aPCC [FEIBA)] within 6 hours prior to initial BAX 802
administration) unless used as a rescue medication (Section 10.5) after failure/study 
withdrawal

Hemophilia medication other than BAX 802 at any time during the study. 
A subject who has taken any of these medications will be considered a protocol deviation.
The following medications and non-drug therapies are permitted within 30 days before 
study entry and during the course of the study:
Medications:

The management of a serious thrombo-embolic event may require anticoagulant 
medication and this may need to be administered concurrent with the use of 
BAX 802 to ensure that a re-bleed or continuing severe hemorrhage does not occur 
on withdrawal of BAX 802 (see Section 10.6). In such instances the Sponsor’s 
medical monitor should be consulted.

Any medications deemed necessary by the subject’s physician to treat or prevent 
any medical condition (with the exception of those listed as not permitted)

Any over-the-counter medication used by the subject to treat symptoms or signs of 
any medical condition

Supplemental vitamins, minerals
Non-drug therapies:

Any non-drug therapy (eg, physiotherapy) deemed necessary by the subject’s 
physician to treat or prevent any medical condition
For non-commercial use only

BAX 802
Page 48 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.6 Rescue Medications
Bypassing agents (FEIBA or NovoSeven) can be used as a rescue medication if expected 
plasma FVIII activity levels are not attained or if bleeding is not controlled despite proper 
dosing of BAX 802 during the intra- or postoperative period of the study. At least 2 doses 
of BAX 802 needs to be administered before the subject is considered to be a treatment 
failure and switched to the rescue medication.
10.7 Subject Completion/Discontinuation
A subject is considered to have completed the study when he/she ceases active 
participation in the study because the subject has, or is presumed to have, completed all 
study procedures according with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation CRF, including: completed, screen failure, AE (eg, death), 
discontinuation by subject (eg, lost to follow-up [defined as 3 documented unsuccessful 
attempts to contact the subject], dropout), physician decision (eg, progressive disease, 
non-compliance with IP/protocol violation(s), recovery), study terminated by sponsor, or
other (reason to be specified by the investigator, eg, technical problems). Regardless of 
the reason, all data available for the subject up to the time of completion/discontinuation 
should be recorded on the appropriate CRF.
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit. If the completion/termination visit is done as an additional, 
unscheduled visit, the assessment results shall be recorded with the 
completion/termination visit. If a subject terminates participation in the study and does 
not return for the completion/termination visit, their last recorded assessments shall 
remain recorded with their last visit. The reason for discontinuation will be recorded, and 
the data collected up to the time of discontinuation will be used in the analysis and 
included in the clinical study report. If additional assessments are required, the 
assessments shall be recorded separately. Assessments to be performed at the termination 
visit (including in cases of withdraw or discontinuation) can be found in Supplement 20.3
and Supplement 20.4.
In the event of subject discontinuation due to an AE, clinical and/or laboratory 
investigations that are beyond the scope of the required study observations/assessments 
may be performed as part of the evaluation of the event. These investigations will take 
place under the direction of the investigator in consultation with the sponsor, and the 
details of the outcome may be reported to the appropriate regulatory authorities by the 
sponsor.
For non-commercial use only

BAX 802
Page 49 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.8 Procedures for Monitoring Subject Compliance
Subject compliance with the procedures and treatment(s) outlined above will be 
monitored by direct review of the subject’s source data at the sites and evaluated against 
the protocol requirements. Additionally, electronic edit checks will be performed on all 
protocol-specified procedures and treatment data that are collected to ensure quality and 
accuracy. Deviations from the protocol-specified procedures and treatments will be noted 
in the final study report.
All study procedures are to be performed under the direct supervision of the 
investigator/a licensed healthcare professional at the study site, and thus, no separate 
procedures will be used to monitor subject compliance.
For non-commercial use only

BAX 802
Page 50 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11. ASSESSMENT OF EFFICACY
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score
The primary outcome measure is the GHEA, which is composed of 3 individual 
categorical ratings which will be added together to form a GHEA score according to 
Table 1 (see Section 8.4.1).
11.2 Secondary Efficacy Endpoints
11.2.1 Blood Loss
The observed versus predicted operative blood loss will be described for the period from 
initiation of the intervention to discharge or 14 days after the intervention (whichever is 
first), as applicable.
Prior to the surgery, the surgeon/investigator will predict the estimated volume (in mL) of 
the expected average and maximum blood loss for the planned surgical intervention in a 
hemostatically normal individual of the same sex, age, and stature as the study subject, 
for intraoperative, postoperative, and overall perioperative time periods. Every effort 
should be made to predict the volume as precisely as possible, also taking into account, 
for example, the use of a tourniquet or placement of a postoperative drain and whether or 
not suction is used. The estimate will be for the intraoperative time period from 
completion of the procedure until approximately 24 hours post-surgery and for the overall 
perioperative time period (assessed at discharge or end of study visit).
The intraoperative blood loss will be measured by determining the volume of blood and 
fluid removal through suction into the collection container (waste box and/or cell saver) 
and the estimated blood loss into swabs and towels during the procedure, per the 
anesthesiologist’s record. Postoperatively, blood loss will be determined by the drainage 
volume collected, which will mainly consist of drainage fluid via vacuum or gravity 
drain, as applicable. In cases where no drain is present, blood loss will be determined by 
the surgeon’s clinical judgment, as applicable or entered as “not available”.
11.2.2 Blood Transfusions
The type and volume (in mL) of blood products will be recorded from initiation of the 
intervention to postoperative Day 14 or discharge (whichever is earlier). Furthermore, 
also salvage of blood obtained from autologous transfusion systems, eg, cell savers, will 
be recorded. In addition, the type and volume of fluid replacement and volume expanders 
will be recorded as concomitant medication (eg, volume of salvaged blood, red blood 
cells, platelets and other blood products transfused).
For non-commercial use only

BAX 802
Page 51 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.3 Bleeding Episodes
Any clinically relevant bleeding episodes (as assessed by the investigator), as well as the 
need for any further surgical interventions, will be recorded. Study subjects will be 
closely monitored for the occurrence of bleeding episodes during the entire intra- and 
postoperative period, until the time of discharge or until the subject resumes his previous 
treatment regimen, whichever is later. 
Any subject who is deemed to have excessive, unexplained bleeding will have blood 
drawn for measurement of FVIII levels. Treatment of such events should be performed as 
per standard of care at the institution.
11.2.4 BAX 802 Administration
The daily and total weight-adjusted administration of BAX 802 per subject will be 
recorded.
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated Bleeding Episodes
An unrelated bleeding episode is defined as any bleeding occurring at a different 
anatomical site than the surgery site during the postoperative period. 

If these unrelated bleeding episodes occur during the subject’s stay in hospital, it is 
recommended that subjects are treated with BAX 802. BAX 802 will be dosed as per 
the most recent residual FVIII activity level and clinical judgment using the dosing 
regimen provided in Table 6 [Required dose = body weight (kg) x desired FVIII rise 
(U/dL or % of normal)]/1.2 (U/kg per U/dL)]. All subsequent dosing of BAX 802
should be preceded by measurement of residual FVIII levels and dose adjustments 
must be based on the most recent residual FVIII activity levels.

If these unrelated bleeding episodes occur after the subject has been discharged, 
subjects will be treated with standard of care, as per investigator’s discretion.
If subject is treated with BAX 802 for unrelated bleeding episodes, the subject will rate 
the severity (minor, moderate, or major) of the bleeding episode and will rate the overall 
treatment response at 24 ±2 hours after the initiation of treatment and at the resolution of 
bleed (if not resolved within 24 hours) using a 4-point efficacy rating scale (Table 7). 
Since the efficacy rating is based to a large degree on cessation of pain, the 
investigator/subject shall, in particular in case of injury-related bleeding into 1 or more 
than 1 location, consider the injury-related symptoms when performing the efficacy
rating 24 hours after initiating treatment and at resolution of bleed.
For non-commercial use only

BAX 802
Page 52 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
As per Table 5, multiple infusions of BAX 802 may be administered for the treatment of 
a bleeding episode. The overall response to all infusions combined is the rating that will 
be recorded at resolution of bleed.
Table 7: Efficacy Rating Scale for Treatment of Unrelated Bleeding Episodes
Excellent
Full relief of pain and/or cessation of objective signs of bleeding (eg, swelling, 
tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) 
after a single infusion. No additional infusion is required for the control of bleeding. 
Administration of further infusions to maintain hemostasis would not affect this scoring.
Good
Definite pain relief and/or improvement in signs of bleeding after a single infusion. 
Possibly requires more than 1 infusion for complete resolution.
Fair
Probable and/or slight relief of pain and slight improvement in signs of bleeding after a 
single infusion. Required more than 1 infusion for complete resolution.
None
No improvement or condition worsens.
11.3 Factor VIII Activity
Blood will be obtained for assessment of FVIII activity at screening (tests to be 
performed at the central laboratory). Results from local laboratory will be used to 
make any dosing decisions.
Blood will be obtained for assessment of FVIII activity for patient management purposes 
at the following timepoints (tests to be performed at the local laboratory, with additional 
back-up samples to be tested in 1 batch at the central laboratory):
Within 30 minutes prior to the administration of the initial loading dose 
preoperatively and 30 ±5 minutes post-infusion. If re-dosing with BAX 802 is 
required to obtain the required FVIII levels, an additional blood sample needs to 
be drawn 30 ±5 minutes following the re-dosing with BAX 802.
Postoperatively until day of discharge from the investigative site: daily within 
30 minutes prior to the infusion of BAX 802 and 30 ±5 minutes post-infusion. 
Pre- and post-dosing blood draws for FVIII activity level determination should 
also be performed for each BAX 802 administration.
FVIII activity will also be assessed if the subject has excessive, unexplained 
bleeding at any time intra-or postoperatively, or whenever deemed necessary 
according to the institution’s standard of care.
For non-commercial use only

BAX 802
Page 53 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.3.1 Blood Sampling and Processing for FVIII Analysis
At each blood sampling time point whole blood will be collected in blood sampling tubes 
will be collected in S-Monovette® tubes (Sarstedt, Nümbrecht, Germany) containing 
3.2% trisodium citrate, or equivalent blood drawing equipment (eg, Vacutainer tubes), 
and immediately mixed. The citrated whole blood samples will be capped and transported 
at room temperature (ie, 20 to 25°C) to the local clinical laboratory for centrifugation, 
processing, and storage. Monovettes must be kept in an upright position at all times to 
avoid leakage.
All samples taken through 6 hours post-dosing will be collected from an extremity other 
than that used for the infusion of study product. Thereafter, either extremity may be used 
to obtain samples.
If the subject has a central venous catheter, the central line should be used to administer 
the infusion and a peripheral venipuncture should be used to collect the blood samples. 
In the event that a blood sample must be drawn through the central line used for 
administration of IP, the line must first be flushed with 5 mL normal saline or other 
suitable catheter flush solution that does not contain anticoagulant. At least 5 mL of 
whole blood must be collected and discarded prior to obtaining the sample. 
All citrated plasma samples will be stored and shipped to the central laboratory at 
≤-70°C for testing. 
All back-up samples collected during the perioperative period will be shipped to the 
central laboratory as soon as possible in 1 batch and analyzed, as needed. 
Blood samples will be analyzed for FVIII activity (1-stage clotting assay and the 
chromogenic assay) at the central laboratory. The 1-stage FVIII activity assay will serve 
as the primary assay; the chromogenic assay of FVIII activity will be used to provide
supportive data. Local laboratories are expected to use a 1-stage clotting assay.
For non-commercial use only

BAX 802
Page 54 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY
12.1 Adverse Events
12.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP 
that does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, 
bacteremia, etc.), or outcome of death temporally associated with the use of an IP, 
whether or not considered causally related to the IP.
12.1.1.1 Serious Adverse Event
A serious adverse event (SAE) is defined as an untoward medical occurrence that at any
dose meets 1 or more of the following criteria:
Outcome is fatal/results in death (including fetal death)
Is life-threatening – defined as an event in which the subject was, in the judgment 
of the investigator, at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death had it been more severe.
Requires inpatient hospitalization or results in prolongation of an existing 
hospitalization – inpatient hospitalization refers to any inpatient admission, 
regardless of length of stay.
Results in persistent or significant disability/incapacity (ie, a substantial disruption 
of a person’s ability to conduct normal life functions)
Is a congenital anomaly/birth defect
Is a medically important event – a medical event that may not be immediately
life-threatening or result in death or require hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the definitions above. Examples of such events are:
Intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependence or drug abuse.
Reviewed and confirmed seroconversion for human immunodeficiency virus 
(HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus 
(HCV), hepatitis E virus (HEV), or parvovirus B19 (B19V).
For non-commercial use only

BAX 802
Page 55 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Thromboembolic events (eg, stroke, myocardial infarction, deep vein 
thrombosis, pulmonary embolism).
Planned hospitalization for any study procedures as per the protocol will not be 
considered as an SAE.
12.1.1.2 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.3 Unexpected Adverse Events
An unexpected adverse event is an AE whose nature, severity, specificity, or outcome is 
not consistent with the term, representation, or description used in the Reference Safety 
Information (RSI). “Unexpected” also refers to the AEs that are mentioned in the IB as 
occurring with a class of drugs or as anticipated from the pharmacological properties of 
the product, but are not specifically mentioned as occurring with the particular product 
under investigation. The expectedness of AEs will be determined by the sponsor using 
the Company core Data Sheet for OBIZUR as the RSI. This determination will include 
considerations such as the number of AEs previously observed, but not on the basis of 
what might be anticipated from the pharmacological properties of a product.
12.1.1.4 Preexisting Diseases
Preexisting diseases that are present before entry in to the study are described in the 
medical history, and those that manifest with the same severity, frequency, or duration 
after IP exposure, will not be recorded as AEs. However, when there is an increase in the 
severity, duration, or frequency of a preexisting disease, the event must be described on
the AE CRF.
12.1.2 Assessment of Adverse Events
For the purposes of this study, the following non-serious events experienced after the first 
IP exposure are collected under other study endpoints and thus are not reportable on the 
AE CRF, nor will they be included in the analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they will 
be assessed as part of the efficacy assessments. However, the investigator may decide 
that the event is an AE if the event also would have occurred in a normal patient under 
the same circumstances. If a bleeding episode was caused by an injury, the injury will be 
reported as an AE.  
For non-commercial use only

BAX 802
Page 56 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
All other/Each AE from the first IP exposure until study completion or discontinuation 
date will be described on the AE CRF using the medical diagnosis (preferred), or, if no 
diagnosis could be established at the time of reporting the AE, a symptom or sign, in 
standard medical terminology in order to avoid the use of vague, ambiguous, or 
colloquial expressions (see definition in Section 12.1). Each AE will be evaluated by the 
investigator for:
Seriousness as defined in Section 12.1.1.1
Severity as defined in Section 12.1.2.1
Causal relationship to IP exposure or study procedure as defined in Section 12.1.2.2
For each AE, the outcome (ie, recovering/resolving, recovered/resolved, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, unknown) and if 
applicable action taken (ie, dose increased, dose not changed, dose reduced, drug 
interrupted, drug withdrawn, not applicable, or unknown) will also be recorded on the AE 
CRF. Recovering/resolving AEs will be followed until resolution, medically stabilized, or
30 days after the study completion/termination visit, whichever comes first. If the 
severity rating for an ongoing AE changes before the event resolves, the original AE 
report will be revised (ie, the event will not be reported as separate AE). During the 
course of any AE, the highest severity rating will be reported.
Deviations from the protocol-specified dosage (including overdosing, underdosing, 
abuse, and withdrawal, treatment errors (including incorrect route of administration, use 
of an incorrect product, and deviations from the protocol-defined dosing schedule), 
failures of expected pharmacological actions, and unexpected therapeutic or clinical 
benefits will be followed with regard to occurrence of AEs, lack of efficacy, and/or other 
observations because these events may be reportable to regulatory authorities.
If an investigator becomes aware of an SAE occurring in a subject after study 
completion, the SAE must be reported on the provided SAE Report Form within 24 hours 
after awareness; no additional reporting on CRFs is necessary.
For non-commercial use only

BAX 802
Page 57 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.1.2.1 Severity
The investigator will assess the severity of each AE using his/her clinical expertise and 
judgment based on the most appropriate description below:
Mild
The AE is a transient discomfort and does not interfere in a significant manner 
with the subject’s normal functioning level.
The AE resolves spontaneously or may require minimal therapeutic 
intervention.
Moderate
The AE produces limited impairment of function and may require therapeutic 
intervention.
The AE produces no sequela/sequelae.
Severe
The AE results in a marked impairment of function and may lead to temporary 
inability to resume usual life pattern.
The AE produces sequela/sequelae, which require (prolonged) therapeutic 
intervention.
These severity definitions will also be used to assess the severity of an AE with a 
study-related procedure(s), if necessary.
12.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, eg, 
assessment of temporal relationships, dechallenge/rechallenge information, association 
(or lack of association) with underlying disease, presence (or absence) of a more likely 
cause, and physiological plausibility. For each AE, the investigator will assess the causal 
relationship between the IP and the AE using his/her clinical expertise and judgment 
according to the following most appropriate algorithm for the circumstances of the AE:
Not related (both circumstances must be met)
Is due to underlying or concurrent illness, complications, concurrent 
treatments, or effects of concurrent drugs
Is not associated with the IP (ie, does not follow a reasonable temporal 
relationship to the administration of IP or has a much more likely alternative 
etiology).
For non-commercial use only

BAX 802
Page 58 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Unlikely related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists
Possibly related (both circumstances must be met)
Follows a reasonable temporal relationship to the administration of IP
An alternative etiology is equally or less likely compared to the potential 
relationship to the IP
Probably related (both circumstances must be met)
Follows a strong temporal relationship to the administration of IP, which may 
include but is not limited to the following:
o
Reappearance of a similar reaction upon re-administration (positive 
rechallenge)
o
Positive results in a drug sensitivity test (skin test, etc.)
o
Toxic level of the IP as evidenced by measurement of the IP 
concentrations in the blood or other bodily fluid
Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related, the investigator shall provide the 
alternative etiology. These causality definitions will also be used to assess the 
relationship of an AE with a study-related procedure(s), if necessary.
12.1.2.3 Safety Reporting
Adverse events/SAEs will be assessed at all study visits as outlined in the Schedule of 
Study Procedures and Assessments (see Table 9) and Section 12.1.
Adverse Events/SAEs are to be recorded on the AE page of the eCRF. Each event should 
be recorded separately.
Any SAE, including death due to any cause, which occurs during this study, whether or 
not related to the IP, must be reported immediately (within 24 hours of the study center’s 
first knowledge of the event). All SAEs must be reported via the Electronic Data Capture 
(EDC) system by completing the relevant electronic Case Report Form (eCRF) page(s) in 
English. For instances in which the EDC may become unavailable, SAEs must be 
reported using the back-up paper SAE Report Form to meet the 24 hour timeline 
requirement (contacts and instructions to be provided in separate documentation). 
For non-commercial use only

BAX 802
Page 59 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Once the EDC becomes available, the site must enter all SAE data as reported on the 
back-up paper SAE report form on the applicable eCRF pages.
The initial SAE information reported on the applicable eCRF pages (or back-up SAE 
Report Form, if applicable) must at least include the following:
Protocol Number
Subject identification number and demographics (gender, age at onset of event 
and/or date of birth)
IP exposure
Medical Term for Event (Diagnosis preferably)
Description of the (S)AE, including:
Date of onset
(S)AE treatment (drug, dose, route of administration)
Causal relationship by the Investigator
Measures taken (ie, action taken regarding IP in direct relationship to the AE)
Seriousness criteria (ie, death, life-threatening, or other criterion)
Cause of death
Autopsy findings (if available)
Name, address, fax number, email, and telephone number of the reporting
Investigator (for paper SAE Report Forms)
12.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the 
protocol, in order to protect subjects participating in a clinical trial from immediate harm. 
Urgent safety measures may be taken by the sponsor or clinical investigator, and may 
include any of the following:
Immediate change in study design or study procedures
Temporary or permanent halt of a given clinical trial or trials
Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety
For non-commercial use only

BAX 802
Page 60 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The investigator may take appropriate urgent safety measures in order to protect subjects 
against any immediate hazard to their health or safety. The measures should be taken 
immediately and may be taken without prior authorization from the sponsor. In the 
event(s) of an apparent immediate hazard to the subject, the investigator will notify the 
sponsor immediately by phone and confirm notification to the sponsor in writing as soon 
as possible, but within 1 calendar day after the change is implemented. The sponsor will 
also ensure the responsible ethics committee(s) and relevant competent authority(s) are 
notified of the urgent safety measures in such cases according to local regulations.
12.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to IP are not 
considered AEs (according to the definition of AE, see Section 12.1). However, each 
serious untoward medical occurrence experienced before the first IP exposure (ie, from 
the time of signed informed consent up to but not including the first IP exposure) will be 
described on the AE CRF (and SAE Report Form if eCRF is not available). These events 
will not be considered as SAEs and will not be included in the analysis of SAEs.
For the purposes of this study, each of the following non-serious events experienced after 
the first exposure to IP will not be considered an AE, and thus, not included in the 
analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they 
will be assessed as part of the efficacy assessments. If a bleeding episode was 
caused by an injury, the injury would not be reported as an AE, unless it resulted in 
a medical finding other than a bleeding episode (eg, abrasion of skin). Therefore, 
any hemophilia-related event (eg, hemarthrosis [presenting as swelling, pain, and 
decreased range of motion], bruising, hemorrhages, or pain at bleeding episode site) 
will not be reported as AEs. However, the Investigator may decide that the event is 
an AE if the event also would have occurred in a normal patient under the same 
circumstances.
12.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to 
identity, quality, durability, reliability, safety and performance of the product but did not 
result in an AE. NMCs include but are not limited to the following:
A failure of a product to exhibit its expected pharmacological activity and/or design 
function, eg reconstitution difficulty
Missing components
For non-commercial use only

BAX 802
Page 61 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Damage to the product or unit carton
A mislabeled product (eg, potential counterfeiting/tampering)
A bacteriological, chemical, or physical change or deterioration of the product 
causing it to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the 
sponsor within 1 business day. If requested, defective product(s) will be returned to the 
sponsor for inspection and analysis according to procedures.
12.5 Medical, Medication, and Non-Drug Therapy History
At screening, the subject’s medical history will be described for the following body 
systems including severity (defined in Section 12.1.2.1) or surgery and start and end 
dates, if known: eyes, ears, nose, and throat; respiratory; cardiovascular; gastrointestinal; 
musculoskeletal; neurological; endocrine; hematopoietic/lymphatic; dermatological; and 
genitourinary.
Medical history will include the collection of hemophilia history, bleeding episode 
history, and history of aPCC or rFVIIA usage for 12 months prior to screening. Relevant 
medical and surgical history and all medications taken 3 months prior to screening will 
also be collected.
All medications taken and non-drug therapies received within 3 months before providing 
informed consent until completion/termination will be recorded on the concomitant 
medications and non-drug therapies CRFs.
12.6 Physical Examinations
At screening and subsequent study visits (as described in Table 9), a physical 
examination will be performed on the following body systems: general appearance, head 
and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and 
joints, lymph nodes, skin, and neurological. At screening, if an abnormal condition is 
detected, the condition will be described on the medical history CRF. At study visits, if a 
new abnormal or worsened abnormal pre-existing condition is detected, the condition will 
be described on the AE CRF. If the abnormal value was not deemed an AE because it 
was due to an error, due to a preexisting disease (described in Section 12.1.1.4), not 
clinically significant, a symptom of a new/worsened condition already recorded as an AE, 
or due to another issue that will be specified, the investigator will record the justification 
on the source record.
For non-commercial use only

BAX 802
Page 62 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7 Clinical Laboratory Parameters
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline 
phosphatase, blood urea nitrogen, creatinine, and glucose.
The hematology panel will consist of complete blood count [hemoglobin, hematocrit, 
erythrocytes (ie, red blood cell count), and leukocytes (ie, white blood cell count)] with 
differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet 
counts.
Clinical chemistry and hematology assessments will be performed on EDTA-
anticoagulated serum and whole blood, respectively, at the central laboratory. The 
frequency of blood draws for clinical and hematology assessments is provided in 
Table 10. 
Details of blood sampling volumes are presented in the laboratory manual and master 
ICF.
12.7.1 Hematology, Clinical Chemistry, and Urinalysis
The hematology panel will consist of complete blood count (hemoglobin, hematocrit, 
erythrocytes [ie, red blood cell count], and leukocytes [ie, white blood cell count]) with 
differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet 
counts.
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, 
creatinine, and glucose.
Blood will be obtained for assessment of hematology and clinical chemistry parameters at 
screening/baseline, all study visits (ie, pre- and perioperatively and daily while the patient 
is at the study site), and at study completion/termination. Hematology and clinical 
chemistry assessments will be performed on EDTA-anticoagulated whole blood and 
serum, respectively, at the central or local laboratory.
The urinalysis panel will consist of pH, protein, ketones, glucose, bilirubin, blood, 
urobilinogen, specific gravity by dipstick and microscopy if any findings are abnormal.
Urine will be obtained for assessment of urinalysis parameters at screening and at study 
completion/termination.
For non-commercial use only

BAX 802
Page 63 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7.2 Viral Serology
Viral serology testing will include HIV-1 and HIV-2 antibody, HAV (immunoglobulin M 
[IgM] and total antibodies), hepatitis B surface antigen (HBsAg), hepatitis B surface 
antibody (HBsAb), hepatitis B core antibody (HBcAb), HCV antibody, and parvovirus 
B19 (IgM and immunoglobulin G [IgG] antibodies). The HIV and HCV titer will be 
confirmed by PCR for all subjects reported as HIV and HCV positive. All viral serology 
assessments will be performed at screening. Any positive HBsAg test will be repeated 
using a new blood sample.
12.7.3 Immunogenicity
Immunogenicity assessments will include anti-pFVIII and hFVIII binding and inhibitory 
antibodies and anti-BHK binding antibodies.
Blood samples will be collected for the assay of anti-pFVIII and hFVIII binding and 
inhibitory antibodies and anti-BHK binding antibodies at the times indicated in Table 9
and Table 10.
All FVIII assays related to study subject management decisions by the investigator will 
be performed at the investigator’s local laboratory.
A central reference laboratory will perform assays (anti-pFVIII, anti-hFVIII, and 
anti-BHK) on samples taken at the Screening, Day 14 or discharge (whichever is earlier), 
and End of Study Visits.
Binding antibodies to pFVIII, hFVIII, and BHK, will be measured using ELISA. The 
assessment of inhibitory antibodies to porcine and hFVIII will be determined using a 
Bethesda assay (with the Nijmegen modification if possible). Further details on blood 
collection, tube preparation and shipment will be provided in the Study Manual.
12.7.4 Assessment of Laboratory Values
12.7.4.1 Assessment of Abnormal Laboratory Values
The investigator’s assessment of each laboratory value will be recorded on the CRF. For 
each abnormal laboratory value, the investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the investigator 
will indicate if the value constitutes an new AE (see definition in Section 12.1, and record
the sign, symptom, or medical diagnosis on the AE CRF), is a symptom or related to a
previously recorded AE, is due to a pre-existing disease (described in Section 12.1.1.4), 
or is due to another issue that will be specified. If the abnormal value was not clinically
significant, the investigator will indicate the reason, ie, because it is due to a preexisting 
For non-commercial use only

BAX 802
Page 64 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
disease, due to a lab error, or due to another issue that will be specified. Additional tests 
and other evaluations required to establish the significance or etiology of an abnormal 
value, or to monitor the course of an AE should be obtained when clinically indicated. 
Any abnormal value that persists should be followed at the discretion of the investigator.
12.7.5 Backup Samples and Biobanking
Backup samples taken and stored short-term may be used for re-testing, follow-up of an 
AE(s) or other test results (such as FVIII activity and antibody testing), and/or assay 
development.
After study testing is completed, the remaining samples may be stored in a coded form 
for no more than 2 years after final study report completion and then the samples will 
subsequently be destroyed.
For this study, no samples will be taken or stored long-term in a biobank for future 
analyses.
12.8 Vital Signs
Vital signs will include body temperature (°C or °F), respiratory rate (breaths/min), pulse 
rate (beats/min), and systolic and diastolic blood pressure (mmHg). Height (in or cm) 
measured once at screening, and weight (lb or kg) will also be collected. 
Vital signs will be measured at screening and within 30 minutes before and 
30 ±5 minutes after administration of IP, at each study visit, and at study
completion/termination. Blood pressure will be measured when subjects are in the
supine position.
Vital sign values are to be recorded on the CRF. For each abnormal vital sign value, the 
investigator will determine whether or not to report an AE (see definition in Section 12.1
and record the medical diagnosis (preferably), symptom, or sign on the AE CRF). 
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
investigator.
For non-commercial use only

BAX 802
Page 65 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.9 Karnofsky Performance Test
The Karnofsky Performance Test is a status scale (0 to 100) utilized to measure the level 
of activity and medical care requirements in subjects. It is an investigator based 
assessment of patient status which evaluates the subjects’ ability to carry on normal life 
activities, as well as the symptoms of their disease.20 Subjects will be scored using this 
scale at screening.
12.10 Special Treatment Considerations
Patients will be screened for eligibility in the study as described in the 
inclusion/exclusion criteria (Section 9.1 and Section 9.2), and will be informed of the 
study specific restrictions and requirements of the study. Patients who are not willing to 
comply with the study requirements and restrictions of the study will not be eligible for 
enrollment.
All biological agents carry the risk of systemic allergic/hypersensitivity reactions. 
Clinical manifestations of these reactions may include, but are not limited to:
skin rash
pruritus (itching)
urticaria (hives)
angioedema (for example, swelling of the lips and/or tongue)
anaphylactic reaction.
Proteins may also cause redness, itching, swelling, or pain locally at the infusion site.
Sometimes, these reactions can be life-threatening. Therefore, all patients should be 
closely monitored for signs or symptoms that could result from such reactions, educated 
on the signs or symptoms of these types of reactions, and instructed to contact the study 
site immediately if any of the symptoms are experienced following an injection. If a 
patient experiences an acute allergic/hypersensitivity reaction after an injection of 
investigational product, he or she should be managed appropriately and given instruction 
to receive relevant supportive care. Additionally, for an event judged by the investigator 
to be a potential systemic allergic/hypersensitivity reaction, a blood sample should be 
drawn to test for anti-drug antibodies.
Patients who experience a potentially severe allergic reaction will be discontinued from 
study drug, they will complete a Termination/Study Completion Visit, and will be 
monitored for stabilization, or resolution of the AE. Premedications to prevent allergic 
reactions will not be permitted as severe allergic reactions are an outcome measure for 
this study. 
For non-commercial use only

BAX 802
Page 66 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. STATISTICS
All details regarding the statistical analysis and the preparation of tables, listings, and 
figures will be described in the statistical analysis plan (SAP). 
13.1 Sample Size and Power Calculations
The sample size of at least 10 surgeries in 10 evaluable male subjects (at least 5 major 
surgeries in 5 evaluable subjects), as defined in the protocol, was chosen to provide 
sufficient evidence of safety and effectiveness for this indication and is not based on 
statistical considerations.
Evaluable subjects are defined as subjects who met all study entry criteria and who had 
all the 3 hemostatic efficacy assessments as per Section 8.4.1.
13.2 Analysis Sets
Classification into the analysis sets will be conducted prior to the database lock.
13.2.1 Safety Analysis Set
The safety analysis set (SAS) will be comprised of all subjects who received any amount 
of BAX 802.
13.2.2 Efficacy Datasets
13.2.2.1 Full Analysis Set 
The full analysis set (FAS) will be comprised of all surgeries with at least 1 available 
hemostatic assessment.
13.2.2.2 Per-Protocol Analysis Set
The per-protocol analysis set (PP) will be comprised of all surgeries with evaluable 
ratings for all 3 perioperative hemostatic efficacy assessments, whom subjects met all 
study entry criteria and had no major protocol violations that might impact hemostatic 
efficacy assessments.
13.3 Handling of Missing, Unused, and Spurious Data
All data will be evaluated as observed; no imputation method for missing values will be 
used. A subject who withdraws prior to the last planned observation in a trial period will 
be included in the analyses up to the time of withdrawal.
For non-commercial use only

BAX 802
Page 67 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4 Methods of Analysis
For qualitative parameters, the population size (N for sample size and n for available 
data) and the percentage (of available data) for each class of parameters will be 
presented. Quantitative parameters will be summarized by the population size (N for 
sample size and n for available data), mean, standard deviation, median, minimum, and 
maximum values.
13.4.1 Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy 
assessed intraoperatively and at postoperative Day 1 (ie, the day following the day of 
surgery) by the surgeon and and perioperatively at Day 14 visit or discharge (whichever 
is earlier) by the investigator (hemophilia physician), and will be summarized by the 
GHEA score and rated “excellent”, “good”, “fair” and “none”.
A treatment success will be defined as a rating of excellent and/or good. 
Owing the possibility of multiple surgeries per subject, the statistical entity on which the
primary outcome measure will be reported is the surgery.
Point estimates and corresponding 2-sided exact confidence intervals (CIs) at the 
90% confidence level will be calculated for the rate of hemostatic efficacy assessments 
with excellent/good outcome.
The primary efficacy analysis will be based on the FAS population. As a supportive 
analysis, the same analyses will also be carried out on the PP population.
Any blood loss which is considered as unrelated bleeding (defined as any bleeding 
occurring at a different anatomical site other than the surgery site during the 
postoperative period, see Section 11.2.5) will not be taken into account for while making 
assessment of hemostatic efficacy for the primary efficacy measure.
13.4.2 Secondary Outcome Measures 
13.4.2.1 Secondary Hemostatic Efficacy Analysis
Where possible, secondary outcome measures will be reported at the surgery level rather 
than the subject level. Descriptive statistics will be used to summarize the actual blood 
loss and transfusion requirements, respectively. 
The summary of average daily and total weight-adjusted doses (average through 
postoperative Day 14 or discharge [whichever is earlier]) of BAX 802 per subject as well 
as the occurrence of bleeding episodes will be provided using descriptive statistics. 
For non-commercial use only

BAX 802
Page 68 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For unrelated bleeding episodes in the postoperative period, descriptive statistics will be 
used to summarize the overall hemostatic efficacy rating at 24 ±2 hours after initiation of 
treatment and at resolution of bleed (if not resolved within 24 hours). Separate descriptive 
summaries of average daily and total weight-adjusted doses required to treat unrelated 
bleeding episodes will be provided.
The secondary efficacy analysis will be performed on the FAS only.
13.4.2.2 Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by presenting the number and percentage of subjects 
having any AE, having an AE in each system organ class, and having each individual AE 
as reported by preferred term. In the summaries, AEs will be counted only once per 
patient. If a patient reports the same AE more than once, it will be counted with its worst 
severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the 
number of IP-related AEs will be tabulated and subcategorized for thrombotic events, 
inhibitory and total binding antibodies to rpFVIII and hFVIII, and binding antibodies to 
BHK proteins.
A listing of all AEs will be presented by subject identifier, age, preferred term, and 
reported term of the AE, duration, severity, seriousness, action taken, outcome, causality 
assessment, onset date, stop date, and medication or non-drug therapy to treat the AE. An 
overview table for AEs will be provided, presenting the number of AEs, the number of 
subjects with AEs and the corresponding percent of subjects in total, and by seriousness 
and relationship to study treatment. An additional summary table will present the total 
number of (mild, moderate, severe) AEs by system organ class and preferred term with 
relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. 
Descriptive statistics of changes from baseline (Day 0 - prior to surgery) by study visits 
will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. 
Furthermore, laboratory abnormalities will be analyzed by shift tables where each subject 
will be counted only once with the worst grade in the summary tables. 
For non-commercial use only

BAX 802
Page 69 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
All laboratory data will be listed with abnormal values.
Vital signs assessments as well as the corresponding changes from baseline will be 
summarized descriptively at each scheduled assessment.
The safety analysis will be based on the SAS.
13.5 Planned Interim Analysis of the Study
No interim analyses are planned for this study.
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The investigator/study site will cooperate and provide direct access to study documents 
and data, including source documentation for monitoring by the study monitor, audits by
the sponsor or sponsor’s representatives, review by the EC, and inspections by applicable 
regulatory authorities, as described in the Clinical Study Agreement. If contacted by an 
applicable regulatory authority, the investigator will notify the sponsor of contact, 
cooperate with the authority, provide the sponsor with copies of all documents received 
from the authority, and allow the sponsor to comment on any responses, as described in 
the Clinical Study Agreement.
For non-commercial use only

BAX 802
Page 70 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable regulatory requirements as described in the 
Clinical Study Agreement. The investigator is ultimately responsible for the conduct of 
all aspects of the study at the study site and verifies by signature the integrity of all data 
transmitted to the sponsor. The term “investigator” as used in this protocol as well as in 
other study documents, refers to the investigator or authorized study personnel that the 
investigator has designated to perform certain duties. Sub-investigators or other 
authorized study personnel are eligible to sign for the investigator, except where the 
investigator’s signature is specifically required.
15.1.1 Investigator Report and Final Clinical Study Report
The investigator, or coordinating investigator(s) for multicenter studies, will sign the 
clinical study report. The coordinating investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the investigator and study site personnel understand all 
requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an investigator. Training may be provided at an investigator’s meeting, 
at the study site, and/or by instruction manuals. In addition, the study monitor will be 
available for consultation with the investigator and will serve as the liaison between the 
study site and the sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts 
the study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable regulatory guidelines/requirements. 
The investigator will permit the study monitor to visit the study site at appropriate 
intervals, as described in the Clinical Study Agreement. Monitoring processes specific to 
the study will be described in the clinical monitoring plan.
15.4 Safety Monitoring
The safety of the subjects in this study shall be monitored by an internal safety 
monitoring committee (ISMC).
The ISMC is an independent group consisting of various Baxalta employees who have 
experience and substantial expertise in the review and evaluation of safety data generated 
from study participants within this disease area and in the monitoring of safety of subjects 
For non-commercial use only

BAX 802
Page 71 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
during the study. The ISMC will have a minimum of three members not directly involved 
with the conduct of the study, one of whom will serve as chair and another as secretary 
documenting decisions and ensuring appropriate communication to the study team. 
Membership of the ISMC will be drawn from Drug Safety/Pharmacovigilance, Clinical 
Research, Clinical Development, Data Management, and Biostatistics, who are not 
actively involved in the conduct of this study. The ISMC will review safety data at 
predefined intervals and make recommendations to the study team and the Program 
Innovation Team on study conduct including dose escalation and modifications to study 
plan. Details of the composition and responsibilities of the ISMC are provided in the 
ISMC charter.
The Sponsor plans to perform a safety analysis when data are available for 5 surgeries 
from adult subjects (with at least 2 major surgeries) to assess the suitability of studying 
BAX 802 in the peri-operative management of pediatric male subjects with CHA with 
inhibitors to hFVIII.
15.5 Auditing
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable regulatory guidelines/requirements. 
The investigator will permit auditors to visit the study site, as described in the Clinical 
Study Agreement. Auditing processes specific to the study will be described in the audit
plan.
15.6 Non-Compliance with the Protocol
The investigator may deviate from the protocol only to eliminate an apparent immediate 
hazard to the subject. In the event(s) of an apparent immediate hazard to the subject, the 
investigator will notify the sponsor immediately by phone and confirm notification to the 
sponsor in writing as soon as possible, but within 1 calendar day after the change is 
implemented. The sponsor (Baxalta) will also ensure the responsible ethics committee is 
notified of the urgent measures taken in such cases according to local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the sponsor may terminate the investigator’s participation. The sponsor will 
notify the EC and applicable regulatory authorities of any investigator termination.
15.7 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments. Local 
laboratories are requested to provide their laboratory specifications for each assay used.
For non-commercial use only

BAX 802
Page 72 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16. ETHICS
16.1 Subject Privacy
The investigator will comply with applicable subject privacy regulations/guidance as 
described in the Clinical Study Agreement.
16.2 Ethics Committee and Regulatory Authorities
Before patients participate in this study, the protocol, informed consent form, any
promotional material/advertisements, and any other written information will be reviewed 
and approved/given favorable opinion by the EC and applicable regulatory authorities. 
The IB will be provided for review. The EC’s composition or a statement that the EC’s 
composition meets applicable regulatory criteria will be documented. The study will 
commence only upon the sponsor’s receipt of approval/favorable opinion from the EC 
and, if required, upon the sponsor’s notification of applicable regulatory authority(s) 
approval, as described in the Clinical Study Agreement.
If the protocol or any other information given to the subject is amended, the revised 
documents will be reviewed and approved/given favorable opinion by the EC and 
applicable regulatory authorities, where applicable. The protocol amendment will only be 
implemented upon the sponsor’s receipt of approval and, if required, upon the sponsor’s 
notification of applicable regulatory authority(s) approval.
16.3 Informed Consent
Investigators will choose patients for participation considering the study eligibility
criteria. The investigator will exercise no selectivity so that no bias is introduced from 
this source.
All patients and/or their legally authorized representative must sign an ICF before 
entering into the study according to applicable regulatory requirements and ICH GCP. An 
assent form may be provided and should be signed by patients less than 18 years of age. 
Before use, the ICF will be reviewed by the sponsor and approved by the EC and 
regulatory authority(s), where applicable, (see Section 16.2). The ICF will include a 
comprehensive explanation of the proposed treatment without any exculpatory
statements, in accordance with the elements required by ICH GCP and applicable 
regulatory requirements. Patients or their legally authorized representative(s) will be 
allowed sufficient time to consider participation in the study. By signing the ICF, patients 
or their legally authorized representative(s) agree that they will complete all evaluations 
required by the study, unless they withdraw voluntarily or are terminated from the study 
for any reason.
For non-commercial use only

BAX 802
Page 73 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The sponsor will provide to the investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The ICF will be 
updated, if necessary. This new information and/or revised informed consent form that 
has been approved by the applicable EC and regulatory authorities, where applicable, will 
be provided by the investigator to the subjects who consented to participate in the study
(see Section 16.3).
For non-commercial use only

BAX 802
Page 74 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The investigator will comply with the confidentiality policy as described in the Clinical 
Study Agreement. 
17.2 Study Documentation and Case Report Forms
The investigator will maintain complete and accurate paper format study documentation 
in a separate file. Study documentation may include information defined as “source data” 
(see Section 8.8), records detailing the progress of the study for each subject, signed 
informed consent forms, correspondence with the EC and the study monitor/sponsor, 
screening information, CRFs, SAE reports (SAERs), laboratory reports (if applicable), 
and data clarifications requested by the sponsor.
The investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry 
will be crossed out entirely, remaining legible; and 2) each correction must be dated and 
initialed by the person correcting the entry; the use of correction fluid and erasing are 
prohibited.
The investigator is responsible for the procurement of data and for the quality of data 
recorded on the CRFs. CRFs will be provided in electronic form.
If electronic format CRFs are provided by the sponsor, only authorized study site 
personnel will record or change data on the CRFs. If data is not entered on the CRFs 
during the study visit, the data will be recorded on paper, and this documentation will be 
considered source documentation. Changes to a CRF will require documentation of the 
reason for each change. An identical (electronic/paper) version of the complete set of 
CRFs for each subject will remain in the investigator file at the study site in accordance 
with the data retention policy (see Section 17.3).
The handling of data by the sponsor, including data quality assurance, will comply with 
regulatory guidelines (eg, ICH GCP) and the standard operating procedures of the 
sponsor. Data management and control processes specific to the study will be described 
in the data management plan.
17.3 Document and Data Retention 
The investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention 
policy, as described in the Clinical Study Agreement.
For non-commercial use only

BAX 802
Page 75 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
18. FINANCING AND INSURANCE
The investigator will comply with investigator financing, investigator/sponsor insurance, 
and subject compensation policies, if applicable, as described in the Clinical Study 
Agreement.
19. PUBLICATION POLICY
The investigator will comply with the publication policy as described in the Clinical 
Study Agreement. 
For non-commercial use only

BAX 802
Page 76 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. SUPPLEMENTS
20.1 Procedures per Study Period
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
1. Screening 
Written Informed Consent must be obtained prior to any study-related procedures
Screening activities should be performed within 45 days prior to the planned elective surgery.
The following screening procedures are required:

Eligibility evaluation (review of inclusion/exclusion criteria)

Hemophilia history, bleeding episode history, history of aPCC or rFVIIA usage for a year prior to 
screening

Relevant medical and surgical history and all medications taken 3 months prior to screening

Review of concomitant medications/non-drug therapies

Complete physical examination (see Section 12.6)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body weight 
and height; see Section 12.8)

Karnofsky performance test assessment (see Section 12.9)

Clinical laboratory assessments (see Table 10).
For non-commercial use only

BAX 802
Page 77 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
2. Preoperative Procedures (Day 0)
Subjects will return to the study site prior to their scheduled surgery as instructed by site staff. Subjects will 
undergo the following procedures:
Prior to surgery
The following procedures should be performed before surgery and must be available by at the latest 2 hours 
before the start of surgery:

Accurate prediction of volume of expected blood loss intraoperatively (from completion of the 
procedure until approximately 24 hours post-surgery) and for the overall perioperative time period 
(up to discharge/end of study [EOS])
Loading Dose and Post Dosing Laboratory Assessment
Within 60 to 120 minutes before initiating surgery, the subject will receive a loading dose of BAX 802 to 
raise the plasma level of FVIII to ≥80% for major and to ≥50% for minor surgical, dental and invasive 
procedures.
Subjects will undergo the following procedures:

Prior to BAX 802 loading dose:

Record AEs, concomitant medication and non-drug therapy use

Physical examination, vital signs (pulse, respiratory rate, blood pressure and temperature) and 
weight

Laboratory Assessments including:
o
Hematology (without differential but including platelets)
o
Clinical chemistry  
o
Within 30 minutes before loading dose, blood draw for:

FVIII activity 

BAX 802 loading dose:

Loading dose of BAX 802 to raise the plasma level of FVIII to ≥80% of normal for major and 
to ≥50% for minor surgical, dental and invasive procedures. It will be administered within 60
to 120 minutes prior to surgery (prior to incision/intubation). 

After BAX 802 loading dose:

Laboratory assessment of FVIII activity: 30 ±5 minutes after infusion of the loading dose

Vital signs (pulse, respiratory rate, blood pressure and temperature) will be recorded 30 minutes 
after infusion

Confirmation that FVIII is adequate just prior to intubation/incision. Administration of 
additional dose of BAX 802, if required. If another dose of BAX 802 is necessary, an additional 
post-infusion FVIII activity determination must be performed 30 ±5 minutes following the 
infusion.

All samples taken through 6 hours post-infusion will be collected from an extremity other than 
that used for the infusion of study product. Thereafter, either extremity may be used to obtain 
samples.
The surgery may begin only if FVIII is in target range (Table 5 and Section 8.7.3.3.2).
Throughout: Monitoring of AEs and concomitant medication and non-drug therapy use.
For non-commercial use only

BAX 802
Page 78 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
3. Intraoperative Procedures (Day 0)
During the surgical procedure:

Record AEs and concomitant medication and non-drug therapy use

Record blood product usage, including salvaged blood, packed red blood cells (pRBC), platelets, 
and other blood products. 

Administer additional BAX 802 infusions according to the dosing regimen (Table 5) 

Record intraoperative blood loss and transfusion requirements
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary, the 
subject will subsequently be withdrawn from this BAX 802 surgery study. 
After the surgical procedure:

Record the volume of blood loss during surgery and total blood product usage, including salvaged 
blood, packed red blood cells (pRBCs), platelets, and other blood products

Assess intraoperative hemostatic efficacy (Part A, Table 2) (at the end of surgery) 

Take sample for FVIII activity immediately after surgery completion, with dose adjustments as 
necessary on the day of surgery (see Section 10.5)

Take sample for FVIII activity within preferably 4 to 6 hours following surgery, with dose 
adjustments as necessary on the day of surgery (see Section 10.5)
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary (see 
Section 10.5), the subject will subsequently be withdrawn from this BAX 802 surgery study.
For non-commercial use only

BAX 802
Page 79 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
4. Postoperative Procedures (Days 1 to 13)

For subjects undergoing major surgery: keep pre-infusion FVIII levels at least at 80% of normal for 
the first postoperative 72 hours and at least at 50% during postoperative Day 4 to Day 7. It is 
recommended that the FVIII levels do not fall below 30% from Day 8 until discharge.

For subjects undergoing minor surgery: keep pre-infusion FVIII levels at least at 50% of normal for 
the first postoperative 72 hours. It is recommended that the FVIII levels do not fall below 30% from 
Day 4 until discharge.
From Postoperative Day 1 (ie, the day following the day of the surgical/invasive procedure), 
and daily until discharge the following assessments will be performed:

Record AEs and concomitant medication and non-drug therapy use

Record blood loss on a daily basis and at drain removal, if applicable

Record transfusion requirements

Global Hemostatic Efficacy Assessment (GHEA):
o
Part B (Table 3): assessment of postoperative hemostatic efficacy of BAX 802
performed at Day 1 by the operating surgeon/investigator
o
Part C (Table 4): assessment of perioperative hemostatic efficacy of BAX 802 at Day 14 
or discharge (whichever is earlier) performed by the investigator
If a subject leaves the facility on the day of the surgery/invasive procedure, it is required to 
have a site visit the next day (Day 1) and at Day 14 to perform the assessments of 
postoperative (Part B) and perioperative (Part C) hemostatic efficacy, respectively.

Perform physical examination and vital signs (pulse, respiratory rate, blood pressure and 
temperature) on Days 1, 2, 3, and 7 post surgery (if a subject remains admitted). 

Blood draws for FVIII activity determination and hematology should be performed coincident 
with an early morning dose to the greatest extent possible.

FVIII activity assays at the local and the central laboratories as per Section 8.7.3.3.3. Additional 
BAX 802 doses will be administered as per Table 5. FVIII activity assays pre infusion (within 
30 minutes) and post infusion (30 ±5 minutes) for each IP administration, and at other time 
points as deemed necessary by the surgeon or investigator throughout the study 
o
1-stage clotting and chromogenic for the central laboratory
o
1-stage clotting for local laboratories

Samples for laboratory testing will be taken daily during Day 1 to 7 post-surgery and then 
subsequently once weekly:
o
Hematology
o
Clinical chemistry

If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by 
whatever means necessary until adequate hemostasis is achieved. If rescue medications become 
necessary, the subject will subsequently be withdrawn from this BAX 802 surgery study.
For non-commercial use only

BAX 802
Page 80 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Flow Diagram of Required Procedures for Baxalta Clinical Study 241502
5. Day 14 ±3 days Visit/Discharge Visit/End of Study [EOS] Visit (Day 42 +7 days)
The Day 14 Visit will be performed if subject has not been discharged by then. The Discharge Visit will be 
performed when the subject is discharged, and the EOS Visit will be performed 42 to 49 days following the 
completion of the surgical procedure. In cases where the Discharge Visit would occur within 3 days of 
either the Day 14 or the EOS visit, the respective visits will be done as a single visit.
Procedures to be performed for each subject at Day 14 Visit/Discharge Visit/EOS Visit:

Perform overall perioperative hemostatic efficacy assessment (Part C) on Day 14 or discharge 
(whichever is earlier) by the investigator (hemophilia physician)

Assessment of blood loss

Assessment of transfusion requirements

Review of concomitant medications/non-drug therapies

Complete physical examination 

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body 
weight)

Clinical laboratory assessments (Table 10)

Immunogenicity assays:

Anti-pFVIII and hFVIII binding and inhibitory antibody titers (Note: these will be performed 
only if at least 72 hours must have elapsed since the previous BAX 802 administration)

Anti-BHK binding antibody titers
6. Optional Antibody Testing Visit
Whenever feasible, a visit will be performed between 7 to 14 days after the subject is discharged. Study 
procedures will be performed as per Table 9 and blood samples will be collected for antibody testings and 
other tests as per Table 10. This visit is optional.
Procedures to be performed for each subject at Optional Antibody Testing Visit:

Immunogenicity assays:

Anti-pFVIII and hFVIII binding and inhibitory antibody titers (Note: these will be performed 
only if at least 72 hours must have elapsed since the previous BAX 802 administration)

Anti-BHK binding antibody titers
Unrelated Bleeding Episodes During the Postoperative Period:
An unrelated bleeding episode is defined as any bleeding occurring at a different anatomical site than the 
surgery site during the postoperative period. Refer to Section 11.2.5, Table 9, and Table 10.
For non-commercial use only

BAX 802
Page 81 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.2 Study Flow Chart
Figure 1: Visit Schedule
For non-commercial use only

BAX 802
Page 82 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.3 Schedule of Study Procedures and Assessments
Table 9: Schedule of Study Procedures and Assessments
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures; 
until subject is 
discharged
Day 14 ±3 or 
Discharge 
(whichever is 
earlier) 
proceduresa
Optional 
Antibody 
Testing 
Visitb
End of Study 
Visitc/ 
Discharge 
proceduresa
Procedure/Assessment
Up to 45 
days 
prior to 
Day 0
Day 0
~1 to 2 hours 
prior to 
surgery
Day 0
During 
surgery
Day 1 to Day 13
Day 14 ±3
Discharge day
Between 7 to 
14 days after 
the Discharge 
day
Day 42 +7
Discharge day
Eligibility criteria, including 
medical historyd
X
Medications and non-drug 
therapies
X
X
X
X
X
X
X
Physical examination
X
X
Xe (as required)
X
X
X
Adverse events
X
X
X
X
X
X
Laboratory assessmentsf
X
X
X
X
X
X
X
Vital signsg
X
Xh
Xh
Xe,h
X
X
X
Karnofsky Performance Test
X
Approved FVIII maintenance 
plan
X
IP treatment
X (loading 
dose; Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
Hemostatic Efficacy 
Assessments
A at the end of 
surgery as per 
Table 2
B at 24 hours 
(Day 1) as per 
Table 3i
C at Day 14 or 
discharge 
(whichever is 
earlier), as per 
Table 4i
Transfusion requirements
X
X
X
X
For non-commercial use only

BAX 802
Page 83 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 9: Schedule of Study Procedures and Assessments
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures; 
until subject is 
discharged
Day 14 ±3 or 
Discharge 
(whichever is 
earlier) 
proceduresa
Optional 
Antibody 
Testing 
Visitb
End of Study 
Visitc/ 
Discharge 
proceduresa
Procedure/Assessment
Up to 45 
days 
prior to 
Day 0
Day 0
~1 to 2 hours 
prior to 
surgery
Day 0
During 
surgery
Day 1 to Day 13
Day 14 ±3
Discharge day
Between 7 to 
14 days after 
the Discharge 
day
Day 42 +7
Discharge day
Procedures for Unrelated Bleeding Episodes During the Postoperative Period (see Section 11.2.5)
Medications and non-drug 
therapies
X
Laboratory assessments
Refer to Table 10
IP treatment
Refer to Table 6
Vital signsg
Xh
Hemostatic Efficacy 
Assessments
At 24 ±2 hours after the initiation of treatment and at the resolution of bleed (if not resolved within 24 hours) 
using a 4-point efficacy rating scale (Table 7)
Transfusion requirements
X
a
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the End of Study Visit, the respective visits will be done as a 
single visit.
b
This visit is optional.
c
This visit also applies to subjects who withdraw or discontinue prematurely.
d
Occurs prior to any study-specific procedures.
e
Perform physical examination and vital signs (pulse, respiratory rate, blood pressure and temperature) on Days 1, 2, 3, and 7 post surgery (if a subject 
remains admitted).
f
For laboratory assessments, see Table 10.
g
Vital signs will include body temperature, pulse rate, blood pressure, respiratory rate, and weight. Blood pressure will be measured when subjects are 
in the supine position. Height, measured once at Screening, will also be collected.
h
Within 30 minutes pre, 30 ±5 minutes post-dose.
i
If the subject is discharged from surgical facility on the day of the procedure, he should attend the site on Day 1 to perform the postoperative 
hemostatic efficacy assessment (Day 1 assessment) and the overall peri-operative assessment. In this case, physical examination, vital signs, laboratory 
assessments, adverse events, and concomitant medications must also be assessed.
For non-commercial use only

BAX 802
Page 84 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.4 Clinical Laboratory Assessments
Table 10: Clinical Laboratory Assessments
Preoperative 
Period
Postoperative Period
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
daily 
procedures; till 
subject is 
discharged
Day 14 ±3 or 
Discharge 
(whichever is 
earlier) 
proceduresa
Optional 
Antibody 
Testing Visitb
End of 
Study Visitc/ 
Discharge 
proceduresa
Assessment
Sample
Up to 
45 days 
prior to 
Day 0
Day 0
~1 to 2 hours 
Prior to 
Surgery
Day 0
During surgery
Day 1 to 
Day 13
Day 14 ±3
Discharge 
day
Between 7 to 
14 days after 
the Discharge 
day
Day 42 +7
Discharge 
day
FVIII activity (clotting 
and chromogenic assay 
at central lab; clotting 
assay at local lab)
Citrated 
plasma
C
L and C within 
30 minutes 
before loading 
dose, then 
30 ±5 minutes 
after loading 
dosed
Optional sampling, 
as deemed 
necessary: L and C
Also, if subject has 
excessive or 
unexplained 
bleeding
L and Ce
L and C
L and C
PT and aPTT
Citrated 
plasma
C and L
Chemistryf
Serum
C
L and C
(L)
L
Daily Days 1 
to 7
C (L)
C (L)
C (L)
Hematology
Whole 
blood
Cg
Lh
(L)
L
Daily Days 1 
to 7
C (L)
C (L)
C (L)
Urinalysis
Urine
C
C
C
C
Viral serologyi
Serumj
C
For non-commercial use only

BAX 802
Page 85 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 10: Clinical Laboratory Assessments
Preoperative 
Period
Postoperative Period
Period
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
daily 
procedures; till 
subject is 
discharged
Day 14 ±3 or 
Discharge 
(whichever is 
earlier) 
proceduresa
Optional 
Antibody 
Testing Visitb
End of 
Study Visitc/ 
Discharge 
proceduresa
Assessment
Sample
Up to 
45 days 
prior to 
Day 0
Day 0
~1 to 2 hours 
Prior to 
Surgery
Day 0
During surgery
Day 1 to 
Day 13
Day 14 ±3
Discharge 
day
Between 7 to 
14 days after 
the Discharge 
day
Day 42 +7
Discharge 
day
Anti-pFVIII and hFVIII 
binding and inhibitory 
antibody titers
Citrated 
plasma
Cg
Ck
C
Ck
Anti-BHK binding 
Antibody titers
Citrated 
plasma
C
C
C
C
Laboratory Assessments for Unrelated Bleeding Episodes During the Postoperative Period (see Section 11.2.5)
FVIII activity (clotting 
and chromogenic assay 
at central lab; clotting 
assay at local lab)
Citrated 
plasma
Refer to Section 11.2.5
Optional sampling, as deemed necessary: L and C
Key: C = central laboratory; L = local laboratory; (L) = local testing optional, to aid in clinical management of patients.
a
In cases where the Discharge Visit would occur within 3 days of either the Day 14 or the End of Study visit, the respective visits will be done as 
a single visit.
b
This visit is optional.
c
This visit also applies to subjects who withdraw or discontinue prematurely.
d
It is recommended that the surgery starts after FVIII levels have achieved target levels. If FVIII activity post loading dose is close to the target level, a 
supplement dose of BAX 802 should be administered without further delaying the surgery. If FVIII activity post loading dose is not close to the target 
level, a supplement dose of BAX 802 should be administered and surgery delayed until FVIII levels have achieved target levels or are in close range.
e
FVIII activity should be monitored postoperatively as per instructions in Section 8.7.3.3.3.
Continued on Next Page
For non-commercial use only

BAX 802
Page 86 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
f
Sodium, potassium, chloride, bicarbonate, protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and 
glucose.
g
Hematology and antibody testing should be performed during the screening at least 2 weeks before the planned surgery day as hematocrit and anti-
pFVIII inhibitor titer values are required for loading dose calculation.
h
Hematology, without differential but including platelets.
i
HIV-1 and HIV-2 antibody, HAV (IgM and total antibodies), HBsAg, HBsAb, HBcAb, HCV Ab, and parvovirus B19 (IgM and IgG antibodies). 
CD4 for HIV positive patients and HCV-RNA or HIV-RNA for confirmatory testing of HIV or HCV positive results, respectively.
j
Citrated plasma for HCV-RNA or HIV-RNA confirmatory testing.
k
To be performed only if at least 72 hours must have elapsed since the previous BAX 802 administration.
For non-commercial use only

BAX 802
Page 87 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.5 Global Efficacy Assessments Scores
Table 11: Combinations of Individual Efficacy Assessments
(A, B, C) and GHEA Score
Individual 
Assessment Scores
(A,B,C)
GHEA
3 3 3
Excellent
3 3 2
Excellent
3 2 2
Excellent
3 3 1
Good
3 2 1
Good
3 1 1
Good
2 2 2
Good
2 2 1
Good
2 1 1
Fair
1 1 1
Fair
3 3 0
None
3 2 0
None
3 1 0
None
3 0 0
None
2 2 0
None
2 1 0
None
2 0 0
None
1 1 0
None
1 0 0
None
0 0 0
None
For non-commercial use only

BAX 802
Page 88 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.6 Definitions
20.6.1 Joint Bleeds
Features of an acute joint bleed include some or all of the following: ‘aura’, pain, 
swelling, warmth of the skin over the joint, decreased range of motion and difficulty in 
using the limb compared with baseline or loss of function. 
The earliest clinical signs of a joint bleed are increased warmth over the area and 
discomfort with movement, particularly at the ends of range.
Later symptoms and signs include pain at rest, swelling, tenderness, and extreme loss of 
motion.
In patients with advanced arthropathy it may be difficult to distinguish pain-related 
arthritis from that associated with an acute bleed. Rapid resolution of pain following 
infusion of factor concentrates (typical of an acute hemarthrosis) or improvement of pain 
associated with activity soon after a period of rest (typical of chronic arthritis) can help 
distinguish between the two.
20.6.2 Muscle Bleeds
Muscle bleeds can occur in any muscle of the body, usually from a direct blow or a 
sudden stretch. A muscle bleed is defined as an episode of bleeding into a muscle, 
determined clinically and/or by imaging studies, generally associated with pain and/or 
swelling and functional impairment over baseline.
For further definitions of CNS, GI and abdominal hemorrhages see the Guidelines for the 
management of hemophilia from the world federation of hemophilia.5,21
For non-commercial use only

BAX 802
Page 89 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES
1. Coppola A, Di Capua M, Di Minno MND et al. Treatment of hemophilia: A review 
of current advances and ongoing issues. J.Blood Med. 2010;1:183-195.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262316/pdf/jbm-1-183.pdf
2. Janbain M, Leissinger CA, Kruse-Jarres R. Acquired hemophilia A: emerging 
treatment options. J.Blood Med. 2015;6:143-150.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431493/pdf/jbm-6-143.pdf
3. Mansouritorghabeh H. Clinical and laboratory approaches to hemophilia A. 
Iran.J.Med.Sci. 2015;40:194-205.
Link to Publisher´s Site: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430880/pdf/ijms-40-194.pdf
4. Berntorp E, Shapiro A, Astermark J et al. Inhibitor treatment in haemophilias A and 
B: summary statement for the 2006 international consensus conference. 
Haemophilia. 2006;12 Suppl 6:1-7.
5. World Federation of Hemophilia Treatment Guidelines Working Group. Guidelines 
for the management of hemophilia 2nd Edition.  76. 2005.  World Federation of 
Hemophilia (WFH). 
Link to Publisher´s Site: http://www1.wfh.org/publication/files/pdf-1472.pdf
For non-commercial use only

BAX 802
Page 90 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. Santagostino E, Escobar M, Ozelo M et al. Recombinant activated factor VII in the 
treatment of bleeds and for the prevention of surgery-related bleeding in congenital 
haemophilia with inhibitors. Blood Rev. 2015;29 Suppl 1:S9-S18.
7. Valentino LA, Cooper DL, Goldstein B. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX. Haemophilia. 2011;17:11-579.
8. Kempton CL, White GC, II. How we treat a hemophilia A patient with a factor VIII 
inhibitor. Blood. 2009;113:11-17.
9. Kasper CK. Effect of prothrombin complex concentrates on factor VIII inhibitor 
levels. Blood. 1979;54:1358-1368.
10. Young G, Sørensen B, Dargaud Y et al. Thrombin generation and whole blood 
viscoelastic assays in the management of hemophilia: current state-of-art and future 
perspectives. Blood. 2013;121:1944-1950.
11. Kempton CL, Abshire TC, Deveras RA et al. Pharmacokinetics and safety of OBI-
1, a recombinant B domain-deleted porcine factor VIII, in subjects with 
haemophilia A. Haemophilia. 2012;18:798-804.
12. Mahlangu J, Andreeva T, Macfarlane D et al. A phase II open-label study 
evaluating the hemostatic activity, pharmacokinetics and safety of recombinant 
porcine factor VIII (OBI-1) in hemophlia A patients with inhibitors directed against 
human FVIII [abstract]. Haemophilia. 2008;14 Suppl 2:15-16.
For non-commercial use only

BAX 802
Page 91 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. Kruse-Jarres R, St Louis J, Greist A et al. Efficacy and safety of OBI-1, an 
antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with 
acquired haemophilia A. Haemophilia. 2015;21:162-170.
14. Baxter Healthcare Corporation. Obizur core data sheet.  7-22-2015. 
15. Brettler DB, Forsberg AD, Levine PH et al. The use of porcine factor VIII 
concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor 
VIII. A multicenter US experience. Arch.Intern.Med. 1989;149:1381-1385.
16. Hay CRM, Lozier JN, Lee CA et al. Safety profile of porcine factor VIII and its use 
as hospital and home-therapy for patients with haemophilia-A and inhibitors: the 
results of an international survey. Thromb.Haemost. 1996;75:25-29.
17. Baxter Healthcare Corporation. Package Insert: OBIZUR [antihemophilic factor 
(recombinant), porcine sequence] lyophilized powder for solution for intravenous 
injection. 10. 2014. OBIZUR. 
18. Lee CA. The evidence behind inhibitor treatment with porcine factor VIII. 
Pathophysiol.Haemost.Thromb. 2002;32 Suppl 1:5-8.
19. Kasper, C. Diagnosis and Management of Inhibitors to Factors VIII and IX - An 
Introductory Discussion for Physicians. Treatment of Hemophilia (34), 22. 2004.  
World Federation of Hemophilia (WFH). 
Link to Publisher´s Site: http://www1.wfh.org/publications/files/pdf-1178.pdf
For non-commercial use only

BAX 802
Page 92 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents 
in cancer. In: MacLeod CM, ed. Evaluation of Chemotherapeutic Agents. New 
York: Columbia University Press; 1949:191-205.
21. Blanchette VS, Key NS, Ljung LR et al. Definitions in hemophilia: Communication 
from the SSC of the ISTH. J.Thromb.Haemost. 2014;12:1935-1939.
For non-commercial use only

BAX 802
Page 93 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
22. SUMMARY OF CHANGES 
Protocol 241502: Amendment 1, 2016 FEB 03
Replaces: Original: 2015 SEP 30
1.
Throughout the document
Description of Change: Minor grammatical and/or administrative changes have 
been made. 
Purpose for Change: To improve the readability and/or clarity of the protocol. 
2.
Synopsis, Secondary Objectives, Secondary Outcome Measure, and Planned 
Statistical Analysis; Section 7.3, Secondary Objectives; Section 8.4.2.1, Efficacy; 
Section 11.2.5, Hemostatic Efficacy Rating for Treatment of Unrelated Bleeding 
Episodes; Section 13.4.1, Primary Outcome Measure; Section 13.4.2.1, Secondary 
Hemostatic Efficacy Analysis; Table 8, Flow Diagram of Required Procedures for 
Baxalta Clinical Study 241502
Description of Change: Change from “intercurrent, unrelated bleeding episodes” to 
“unrelated bleeding episodes.
Purpose for Change: Editorial.
3.
Synopsis, Primary Outcome Measure, Secondary Outcome Measures, and Planned 
Statistical Analysis; Section 8.4.1, Primary Outcome Measure; Table 4, 
Postoperative Efficacy Assessment Scale (Day 14); Section 8.4.2.1, Efficacy; 
Section 11.2.2, Blood Transfusions; Section 12.7.3, Immunogenicity; Table 8, Flow 
Diagram of Required Procedures for Baxalta Clinical Study 241502; Table 9, 
Schedule of Study Procedures and Assessments
Description of Change: Amended “Day 14” to “Day 14 or discharge (whichever is 
earlier)”. In addition, “postoperative” was amended to read “overall perioperative”. 
Table 4 was amended in line with the changes detailed.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
4.
Synopsis, Secondary Objectives; Section 7.3, Secondary Objectives; 
Section 8.4.2.1, Efficacy
Description of Change: Clarity added regarding the “overall perioperative” time 
point. Changed as follows: “Intra- and postoperative and overall perioperative
blood loss compared to the estimated volume of expected average blood loss and 
expected maximum blood loss in a comparable healthy individual as predicted 
preoperatively by the investigator/surgeon…”
For non-commercial use only

BAX 802
Page 94 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
5.
Synopsis, Secondary Outcome Measures; Section 8.4.2.1, Efficacy
Description of Change: “Intra- and postoperative blood loss” changed to “Blood 
loss…”
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
6.
Synopsis, Active Product; Section 8.7.3.3.3, Postoperative Dosing; Section 11.3, 
Factor VIII Activity
Description of Change: Change from “intravenous bolus” to “intravenous infusion”
and from “re-bolus” to “re-dosing”.
Purpose for Change: Changed as given as intravenous infusion and not bolus.
7.
Synopsis, Subject Selection
Description of Change: “10 evaluable adult male subjects (≥ 18 to ≤ 65 years old) 
with CHA with inhibitors to FVIII undergoing surgical and other invasive 
procedures for efficacy and safety evaluation” deleted.
Purpose for Change: Editorial.
8.
Synopsis, Inclusion Criteria; Section 9.1, Inclusion Criteria
Description of Change: Change in inclusion criterion 5 to “Subject is not currently 
receiving or has recently received (< 30 days) ITI therapy”.
Purpose for Change: To clarify the washout period for ITI therapy.
9.
Synopsis, Exclusion Criteria; Section 9.2, Exclusion Criteria
Description of Change: Change in exclusion criterion 7 to “Subject has another 
active coagulation disorder, other than hemophilia A, as per the medical history”.
Change in exclusion criterion 10 to remove “OR subject has been exposed to 
rpFVIII (OBIZUR) before”.
Purpose for Change: To clarify that another active coagulation disorder can be 
documented as per the medical history and to remove exclusion regarding 
OBIZUR.
10.
Synopsis, Study Design and Sample Size Calculation; Section 6.3, Population To 
Be Studied; Section 8.1, Brief Summary; Section 8.2, Overall Study Design; 
Section 13.1, Sample Size and Power Calculation
For non-commercial use only

BAX 802
Page 95 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Description of Change: Clarity added regarding the sample size of 10 being based 
on at least 10 surgeries in 10 evaluable male subjects and at least 5 surgeries in 
5 evaluable subjects.
Purpose for Change: To ensure sufficient evidence is gathered regarding safety and 
effectiveness for BAX 802 in this indication.
11.
Synopsis, Planned Statistical Analysis; Section 13.2.2.1, Full Analysis Set; 
Section 13.2.2.2, Per-Protocol Analysis Set
Description of Change: Definitions of FAS and PP analysis set amended. Second 
paragraph deleted.
Purpose for Change: To clarify analysis set definitions.
12.
Synopsis, Planned Statistical Analysis; Section 13.4.1, Primary Outcome Measure; 
Section 13.4.2.1, Secondary Hemostatic Efficacy Analysis
Description of Change: The primary outcome measure was clarified in line with 
changes to Section 8.4.1, clarity added regarding unrelated bleeding, and details 
added regarding the primary outcome measure in the case of multiple surgeries and 
reporting of secondary outcome measures at the surgery rather than subject level.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
13.
Section 5, List of Abbreviations
Description of Change: Added new abbreviations (aPTT, AST, RSI). Added 
“Continued” at the top of each page of the List of Abbreviations per Baxalta style 
guide.
Purpose for Change: Administrative.
14.
Section 5, List of Abbreviations; Section 6.6, Compliance Statement
Description of Change: Definition of ICH amended to “International Council for 
Harmonisation”.
Purpose for Change: Administrative.
15.
Section 6.4.2, Findings from Clinical Studies
Description of Change: Text updated with the following “As of 2015 December 31, 
there have been 4 post-marketing spontaneous serious adverse event reports. The 
reports were considered possibly associated and consistent with the known safety 
profile of OBIZUR®”.
Purpose for Change: To align with current information.
For non-commercial use only

BAX 802
Page 96 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16.
Section 6.6, Compliance Statement; Section 10.1, Informed Consent; Section 10.2, 
Subject Identification Code; Section 10.3, Screening and Study Visits; 
Section 12.1.1.3, Unexpected Adverse Events; Section 12.1.2.3, Safety Reporting; 
Section 12.2, Urgent Safety Measures; Section 12.5, Medical, Medication, and 
Non-Drug Therapy History; Section 12.7.5, Backup Samples and Biobanking; 
Section 13.2, Analysis Sets; Section 15.5, Auditing; Section 16.2, Ethics 
Committee and Regulatory Authorities; Section 16.3, Informed Consent; 
Section 17.2, Study Documentation and Case Report Forms; Table 9, Schedule of 
Study Procedures and Assessments
Description of Change: Minor changes have been made to align the protocol with 
standard text presented in the current Baxalta protocol template.
Purpose for Change: Administrative.
17.
Section 8.2, Overall Study Design
Description of Change: Deletion of the text as follows: “Subjects may undergo 
more than 1 surgery or 2 parallel surgeries, such as bilateral knee replacement, 
however, in these cases prior approval by the sponsor is required” and text added to 
describe the process to be followed for subjects undergoing multiple surgeries 
(other than parallel surgeries).
Purpose for Change: To remove requirement for sponsor approval and to provide 
clarity regarding visits for subjects undergoing multiple surgeries.
18.
Section 8.2.2, Dose Selection Rationale
Description of Change: Deletion of the following text: “This regimen for loading 
dose of BAX 802 proposed for Study BAX 802 Surgery takes into account the titer 
of anti-pFVIII inhibitors”.
Purpose for Change: Editorial.
19.
Section 8.4.1, Primary Outcome Measure
Description of Change: Addition of the following text: “The assessment of primary 
outcome measure (GHEA score) should only account for the blood loss related to 
the surgery and exclude any blood loss which is considered as unrelated bleeding 
(defined as any bleeding occurring at a different anatomical site than the surgery 
site during the postoperative period, see Section 11.2.5)”.
Purpose for Change: Revised to make distinction between blood loss due to surgery 
and unrelated blood loss.
For non-commercial use only

BAX 802
Page 97 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.
Section 8.7.3.1, FVIII Maintenance Plan
Description of Change: Addition of the following text: “It is recommended that the 
turnaround time for FVIII activity results from the local laboratories are ≤2 hours 
so that dosing decisions could be made and subjects are dosed adequately”.
Purpose for Change: Revised as good turnaround time will ensure that subjects are 
dosed as needed, and also allows better monitoring.
21.
Section 8.7.3.3.1, General; Table 5, Dosing for Perioperative Management
Description of Change: Deletion of the following text: “The dose and frequency of 
BAX 802 administered will be individualized based on the subject’s PK parameters 
for major surgeries and the most recent IR value for minor surgeries and the 
required FVIII target levels”. In addition, the units in the “Required dose” 
calculation were amended from “IU” to “U”, while clarity was added to Table 5 
regarding subjects not yet being discharged and a 1- to 2-hour window for 
administration of the loading dose prior to surgery was added.
Purpose for Change: Pharmacokinetic parameters are not being measured in this 
study.
22.
Section 8.7.3.3.2, Preoperative and Loading Dose
Description of Change: Clarity added regarding a 1 to 2 hour window for 
administration of the loading dose prior to surgery. In case of surgery, FVIII target 
levels amended to ≥80% for major surgeries/procedures and ≥50% for minor 
surgeries/procedures. In addition, recommendations were added/clarified.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
23.
Section 8.7.3.3.3, Postoperative Dosing
Description of Change: Section replaced with new text.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
24.
Section 8.7.3.3.4, Dosing for Unrelated Bleeding Episodes During the 
Postoperative Period
Description of Change: Text amended as follows: “Infusions given to maintain 
hemostatis treat and control the unrelated bleeding episode should be documented 
in the eCRF”.
Purpose for Change: Editorial.
For non-commercial use only

BAX 802
Page 98 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
25.
Table 6, BAX 802 Treatment Guidelines for Unrelated Bleeding Episodes
Description of Change: Units amended from “IU” to “U”, “Loading Dose” and 
“Subsequent Dose” columns replaced with 1 “BAX 802 Dose” column, footnotes 
updated, other minor edits.
Purpose for Change: Administrative.
26.
Section 8.8, Source Data
Description of Change: Statement added regarding data not being entered directly 
onto the CRF.
Purpose for Change: Administrative.
27.
Section 10.4.2, Unscheduled Visits for Unrelated Bleeding Episodes
Description of Change: Section 10.4.2 replaced with new section on “Optional 
Antibody Testing Visit”. Details of the optional antibody testing visit also added to 
Table 8.
Purpose for Change: Unscheduled visits no longer applies, while a visit for testing 
of antibody titers has been added. The antibody testing visit is optional so that there 
will be no additional burden on subjects; it will be done when feasible.
28.
Section 11.2.5, Hemostatic Efficacy Rating for Treatment of Inter-current, 
Unrelated Bleeding Episodes; Table 8, Flow Diagram of Required Procedures for 
Baxalta Clinical Study 241502
Description of Change: Clarity added regarding the treatment of unrelated bleeding 
episodes occurring during the subject’s stay in hospital.
Purpose for Change: To provide clearer information.
29.
Table 7, Efficacy Rating Scale for Treatment of Bleeding Episodes
Description of Change: Clarified that table refers to “unrelated” bleeding episodes.
Purpose for Change: Administrative.
30.
Section 11.3, Factor VIII Activity; Table 8, Flow Diagram of Required Procedures 
for Baxalta Clinical Study 241502; Table 10, Clinical Laboratory Assessments
Description of Change: Timing of collection of preoperative blood samples for 
assessment of FVIII activity amended from 60 to 30 minutes prior to the 
administration of the initial loading dose, and timing for collection of postoperative 
blood samples for assessment of FVIII activity amended from 15 to 30 ±5 minutes 
post-infusion.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
For non-commercial use only

BAX 802
Page 99 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
31.
Section 11.3.1, Blood Sampling and Processing for FVIII Analysis; Table 8, Flow 
Diagram of Required Procedures for Baxalta Clinical Study 241502; Table 10, 
Clinical Laboratory Assessments
Description of Change: Clarified that local laboratories will only use a 1-stage 
clotting assay for determination of FVIII activity.
Purpose for Change: Administrative.
32.
Section 12.7, Clinical Laboratory Parameters; Section 12.7.1, Hematology, Clinical 
Chemistry, and Urinalysis; Table 10, Clinical Laboratory Assessments
Description of Change: Aspartate aminotransferase added to clinical chemistry 
panel, and “bilirubin” amended to “total bilirubin”.
Purpose for Change: AST was inadvertently omitted from the original protocol and 
clarification was added regarding total bilirubin to avoid confusion with direct or 
indirect bilirubin.
33.
Section 12.7.2, Viral Serology
Description of Change: HAV antibody replaced with HAV IgM and total antibodies 
and HBsAb and HBcAb added. In addition, clarity added that HIV titer was also to
be confirmed by PCR for all subjects reported as HIV positive and that any positive 
HBsAg test was to be repeated using a new blood sample.
Purpose for Change: To clarify the specific serology testing to be performed.
34.
Section 12.7.3, Immunogenicity
Description of Change: Reference to BAX 802 inhibitor assay, local laboratories, 
and reference for details of laboratory pre-qualification removed.
Purpose for Change: Editorial.
35.
Section 12.7.5, Backup Samples and Biobanking
Description of Change: Examples of “other test results” added; FVIII activity and 
antibody testing.
Purpose for Change: Editorial.
36.
Section 12.8, Vital Signs; Table 8, Flow Diagram of Required Procedures for 
Baxalta Clinical Study 241502; Table 9, Schedule of Study Procedures and 
Assessments
Description of Change: Timing of measurement of vital signs amended from 15 to 
30 ±5 minutes after administration of IP.
Purpose for Change: To ensure that the safety data is captured at the appropriate 
time.
For non-commercial use only

BAX 802
Page 100 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
37.
Section 13, Statistics
Description of Change: Text deleted as follows: “Data handling will be the 
responsibility of the contract research organization (CRO). The data will be 
inspected for inconsistencies by performing validation checks.
All details regarding the statistical analysis and the preparation of tables, listings, 
and figures will be described in the statistical analysis plan (SAP) prepared by the 
CRO and approved by the sponsor before database lock”.
Purpose for Change: Not standard Baxalta template text.
38.
Section 13.1, Sample Size and Power Calculations
Description of Change: Text added as follows: “Evaluable subjects are defined as 
subjects who met all study entry criteria and who had all the 3 hemostatic efficacy 
assessments as per Section 8.4.1”.
Purpose for Change: Administrative.
39.
Section 13.5, Planned Interim Analysis of the Study
Description of Change: Section amended to reflect that no interim analyses are 
planned for this study.
Purpose for Change: Administrative.
40.
Section 15.4, Safety Monitoring; Section 16.4, Data Monitoring Committee
Description of Change: Updated to include details of ISMC, new section added,
and details from Section 16.4 integrated with new section to align with current 
Baxalta protocol template; Section 16.4 deleted.
Purpose for Change: Administrative.
41.
Table 8, Flow Diagram of Required Procedures for Baxalta Clinical Study 241502; 
Table 10, Clinical Laboratory Assessments
Description of Change: Timing of sample collection for FVIII activity on Day 0 
updated. In addition, under “Procedures to be performed for each subject at Day 14 
Visit/Discharge Visit/EOS Visit”, text has been changed as follows: “Perform 
Postoperative Hemostatic Efficacy Assessment overall perioperative efficacy 
assessment (Part C) on Day 14 or discharge (whichever is earlier) by the 
investigator (hemophilia physician).” Timing for administration of the loading dose 
prior to surgery amended to a 1 to 2 hour window.
Purpose for Change: To ensure that the efficacy data is captured at the appropriate 
time.
For non-commercial use only

BAX 802
Page 101 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
42.
Section 20.2, Study Flow Chart
Description of Change: Figure 1 (Visit Schedule) replaced with new figure.
Purpose for Change: For consistency with changes to earlier protocol sections.
43.
Table 9, Schedule of Study Procedures and Assessments
Description of Change: Additional information added, including procedures for 
unrelated bleeding episodes during the postoperative period, and optional antibody 
testing visit added.
Purpose for Change: To add clarity and include relevant information regarding 
assessments needed for unrelated bleeding.
44.
Table 10, Clinical Laboratory Assessments
Description of Change: aPTT added to assessments, footnotes updated, additional 
information added regarding laboratory assessments for unrelated bleeding 
episodes during the postoperative period, back-up samples for central laboratory 
testing of FVIII activity removed, and optional antibody testing visit added.
Purpose for Change: To ensure that the clinical laboratory assessments are captured 
at the appropriate time.
45.
Table 11, Schedule of Study Procedures and Assessments for Unrelated Bleeding 
Episodes
Description of Change: Table deleted.
Purpose for Change: Deleted as now addressed in Tables 9 and 10.
For non-commercial use only

BAX 802
Page 102 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety 
of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in the Treatment 
of Subjects with Congenital Hemophilia A with Factor VIII Inhibitors Undergoing 
Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 1: 2016 FEB 03
Replaces: ORIGINAL: 2015 SEP 30
OTHER ID(s)
NCT Number: to be determined
EudraCT Number: to be determined
IND NUMBER: to be determined
By signing below, the investigator acknowledges that he/she has read and understands 
this protocol, and will comply with the requirements for obtaining informed consent from 
all study subjects prior to initiating any protocol-specific procedures, obtaining written 
initial and ongoing EC(s) protocol review and approval, understands and abides by the 
requirements for maintenance of source documentation, and provides assurance that this 
study will be conducted according to all requirements as defined in this protocol, clinical 
study agreement, ICH GCP guidelines, and all applicable regulatory requirements.
Signature of Principal Investigator
Date
Print Name of Principal Investigator
For non-commercial use only

BAX 802
Page 103 of 103
Clinical Study Protocol Identifier: 241502
2016 FEB 03
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety 
of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in the Treatment 
of Subjects with Congenital Hemophilia A with Factor VIII Inhibitors Undergoing 
Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 1: 2016 FEB 03
Replaces: ORIGINAL: 2015 SEP 30
OTHER ID(s)
NCT Number: to be determined
EudraCT Number: to be determined
IND NUMBER: to be determined
By signing below, the investigator acknowledges that he/she has read and understands 
this protocol, and provides assurance that this study will be conducted according to all 
requirements as defined in this protocol, clinical study agreement, ICH GCP guidelines, 
and all applicable regulatory requirements.
Signature of Coordinating Investigator
Date
Print Name and Title of Coordinating Investigator
Signature of Sponsor Representative
Date
, MD
, Clinical Development
For non-commercial use only

BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
CLINICAL STUDY PROTOCOL
PRODUCT: BAX 802
STUDY TITLE:
A Phase 3, Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of 
B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects with 
Congenital Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or Other 
Invasive Procedures
STUDY SHORT TITLE: BAX 802 in Congenital Hemophilia A with Inhibitors
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 4: 2017 JUN 28
Replaces:
AMENDMENT 1: 2016 FEB 03
ALL VERSIONS: 
Amendment 4: 2017 JUN 28
Amendment 3 (Russia): 2017 FEB 07
Amendment 2 (Italy): 2016 AUG 22
Amendment 1: 2016 FEB 03
Original: 2015 SEP 30
OTHER ID(s)
NCT Number:
NCT02895945
EudraCT Number:
2015-005521-39
IND NUMBER: 
BB-IND 014798
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362, 
UNITED STATES
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna, 
AUSTRIA
For non-commercial use only

BAX 802
Page 2 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
, Clinical Programs and Therapeutic Area Head
Baxalta Innovations GmbH
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with 
the study (e.g., Investigator(s), sponsor’s medical expert and study monitor, sponsor’s 
representative(s), laboratories, steering committees, and oversight committees (including 
ethics committees [ECs], as applicable) will be maintained by the sponsor and provided 
to the Investigator.
For non-commercial use only

BAX 802
Page 3 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. SERIOUS ADVERSE EVENT REPORTING
The Investigator will comply with applicable laws/requirements for reporting serious 
adverse events (SAEs) to the ECs.
ALL SAEs, INCLUDING SUSPECTED UNEXPECTED SERIOUS ADVERSE 
REACTIONS (SUSARs), ARE TO BE REPORTED ON THE ADVERSE 
EVENT CASE REPORT FORM (CRF) WITHIN 24 HOURS AFTER 
BECOMING AWARE OF THE EVENT. IF THE CRF IS NOT AVAILABLE,
THEN THE SAE MUST BE REPORTED ON THE SERIOUS ADVERSE 
EVENT REPORT (SAER) FORM AND TRANSMITTED TO THE SPONSOR
TO MEET THE 24-HOUR TIMELINE REQIREMENT.
Drug Safety contact information: see SAER form
Refer to SAE Protocol Sections and the study team roster for further 
information.
For definitions and information on the assessment of these events, refer to the following:
AEs, Section 12.1
SAE, Section 12.1.1.1
SUSARs, Section 12.1.1.2
Assessment of AEs, Section 12.1.2
For non-commercial use only

BAX 802
Page 4 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
3. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of Investigational Product (IP)
BAX 802
Name(s) of Active Ingredient(s)
Recombinant Porcine Factor VIII (rpFVIII)
CLINICAL CONDITION(S)/INDICATION(S)
Congenital hemophilia A (CHA) patients with inhibitors to Factor VIII (FVIII) undergoing surgical and 
other invasive procedures
PROTOCOL ID
241502
PROTOCOL TITLE
A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine 
Factor VIII (BAX 802) in Subjects with Congenital 
Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or 
Other Invasive Procedures
Short Title
BAX 802 in CHA with Inhibitors 
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2016, FEB
Primary Completion
2019, MAR
Study Completion
2019 MAR
Duration
Approximately 21 months
STUDY OBJECTIVES AND PURPOSE
Study Purpose
To evaluate the efficacy and safety of BAX 802 in males with CHA with inhibitors who are undergoing 
major or minor elective surgical, dental, or other invasive procedures.
Primary Objective
To evaluate the perioperative hemostatic efficacy of BAX 802 in male subjects with CHA with inhibitors 
to human factor VIII (hFVIII) undergoing major or minor elective surgical, dental, or other invasive 
procedures as determined by the Global Hemostatic Efficacy Assessment (GHEA) score.
Secondary Objectives
1. To determine the safety of BAX 802 used in the perioperative setting by assessing:

The development of and change in titer of anti-porcine FVIII (pFVIII) and anti-hFVIII antibodies 
(binding and neutralizing), and development of binding antibodies to baby hamster kidney (BHK) 
proteins

The occurrence of thrombo-embolic events and/or allergic reactions to BAX 802

The occurrence of adverse events (AEs) related to BAX 802
For non-commercial use only

BAX 802
Page 5 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

The occurrence of clinically significant changes in vital signs and routine laboratory parameters 
related to BAX 802
2. To determine the intraoperative, postoperative, and overall perioperative blood loss, compared to the 
estimated volume of expected average and maximum blood loss in a comparable healthy individual 
as predicted preoperatively by the Investigator/surgeon
3. To determine the proportion of major surgeries with good or excellent hemostatic score
4. To determine the daily and total weight-adjusted administration of BAX 802 per subject
Exploratory objectives 
 
 
 
 
STUDY DESIGN
Study Type/ Classification/ 
Discipline
Efficacy and Safety
Control Type
No control arm
Study Indication Type
Treatment
Intervention model
Single-group
Blinding/Masking
Open-label
Study Design
This study is a Phase 3, prospective, single-arm, open-label, uncontrolled, 
multicenter study to evaluate the efficacy and safety of BAX 802 in at 
least 12 procedures in 12 evaluable male subjects with CHA with 
inhibitors to hFVIII who are undergoing major or minor elective surgical, 
dental or other invasive procedures. The study will be conducted globally 
and will be divided into 5 periods: Screening, Preoperative, Intraoperative, 
Postoperative, and End of study.
Subject Selection
At least 5 of the procedures must be major surgeries in 5 evaluable 
subjects, of which no more than 20% can be dental or other non-operative 
invasive procedures. Elective surgical procedures will prospectively be 
defined as major or minor by the Investigator/surgeon, based on the 
protocol guidance and definitions and in consideration of each subject’s 
characteristics. Emergency surgeries are not in the scope of this study. 
For non-commercial use only

BAX 802
Page 6 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Subjects may undergo more than 1 surgery or 2 parallel surgeries, such as 
bilateral knee replacement, however in these cases prior approval by the 
sponsor is required. In order to evaluate the activity of the product with 
respect to high-titer or high-responding inhibitors, at least 3 adult subjects 
with screening anti-hFVIII inhibitory antibody titers of ≥5 Bethesda units 
(BU) will be enrolled in the study.
Planned Duration of 
Subject Participation
The duration of subject participation depends on the nature of the invasive 
procedure: it will run from the signing of the informed consent until 
completion of the End of Study Visit (at least 5 weeks post-last dose).
Primary Outcome Measure 
The primary outcome measure is the proportion of all surgical, dental, or other invasive procedures with a 
“good” or “excellent” response as measured by GHEA score, which is composed of 3 individual ratings:

GHEA1: Assessment of intraoperative (Day 0) hemostatic efficacy of BAX 802 performed by the 
operating surgeon at the end of surgery.

GHEA2: Assessment of postoperative hemostatic efficacy of BAX 802 at postoperative Day 1 
(approximately 24 hours [±6 hours] post-surgery performed by the operating surgeon. If a patient is 
discharged < 24 hours following surgery, then the GHEA2 hemostatic efficacy assessment may 
require a return visit the following day.

GHEA3: Assessment of overall perioperative hemostatic efficacy of BAX 802 at discharge or within 
24 to 72 hours after the last perioperative treatment dose of BAX 802 if hospitalization is prolonged 
for reasons other than perioperative procedures (whichever is earlier), performed by the Investigator, 
and where possible, also by the operating surgeon. Assessment by both is strongly recommended. In 
cases where there are differing assessments, the Investigator’s assessment will be used. 
The scores of each of the 3 individual ratings described above (GHEA1, GHEA2, and GHEA3), will be 
added together to form a GHEA score. Hemostatic efficacy success is defined as an “excellent” or “good 
“outcome for ≥ 70% of hemostatic efficacy assessments.
Secondary Outcome Measures 
Efficacy 
1. Intra- and post-operative blood loss compared to the estimated volume of expected average blood 
loss and expected maximum blood loss in a comparable healthy individual with similar demographic 
characteristics as predicted preoperatively by the Investigator/surgeon at the following time points:

Intraoperative, from start until the end of surgery

Postoperative Day 1, from end of surgery to approximately 24 hours ±6 hours after surgery

Overall perioperative at discharge or 24 to 72 hours after the last perioperative treatment dose of 
BAX 802 (whichever is earlier)
2. Proportion of major surgeries with good or excellent hemostatic outcome together with its 2-sided 
95% confidence interval
3. Daily and total weight-adjusted administration of BAX 802 per subject
4. Amount of blood, red blood cells, platelets, and other blood products transfused
For non-commercial use only

BAX 802
Page 7 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Safety
1. Development of, and changes to, the titer of inhibitory and binding antibodies immunoglobulin G 
(IgG) and immunoglobulin M (IgM) to pFVIII
2. Development of, and changes to, the titer of inhibitory and binding antibodies (IgG and IgM) to 
hFVIII
3. Development of binding antibodies to BHK proteins
4. Occurrence of thrombo-embolic events
5. Incidence of severe allergic reactions (e.g., anaphylaxis)
6. Incidence of other IP-related AEs
7. Incidence of clinically significant changes in vital signs and routine laboratory parameters 
(hematology, clinical chemistry)
Exploratory Outcomes Measures
 
 
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Active Product
Dosage form: Injectable reconstituted solution of BAX 802, rpFVIII from 
which the B domain has been deleted.
Dosage frequency: Loading dose, followed by subsequent individualized 
dosing.
Mode of Administration: Intravenous bolus infusion (to the cubital vein is 
the recommended anatomical site of administration).
SUBJECT SELECTION
Targeted Accrual
Enroll approximately 12 evaluable subjects (2 of which will be adolescents 
≥ 12 to < 18 years old) for approximately 12 procedures.
Number of 
Groups/Arms/Cohorts
Single-arm
For non-commercial use only

BAX 802
Page 8 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Inclusion Criteria
1. Subject requires a major or minor elective surgical, dental or other invasive procedure
2. Subject is male and ≥ 12 to ≤ 75 years old at the time of screening
3. Subject has provided signed informed consent (and assent for adolescent subjects, as applicable) in 
accordance with local regulatory requirements
4. Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤ 2%) CHA with inhibitors 
to human FVIII (hFVIII), of ≥ 0.6 BU, as tested at screening at the central laboratory
5. Subject is not currently receiving or has recently received (< 30 days) immune tolerance induction 
(ITI) therapy
6. Subject has a Karnofsky performance score of ≥ 60 at screening
7. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and 
CD4+ count ≥ 200 cells/mm3 at screening
8. Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; 
or HCV+ with chronic stable hepatitis disease. (If positive, the antibody titer will be confirmed by 
PCR.)
9. Subject is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
1. The subject 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 FVIII (pFVIII) > 10 BU prior to surgery
5. Platelet count < 100,000/µL at screening
6. Subject has another active coagulation disorder, other than hemophilia A, as per the medical history
7. Planned use of α-interferon with or without ribavarin 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 rpFVIII, or hamster or murine proteins
9. Subject has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, 
fibrinolysis or disseminated intravascular coagulation (DIC).
10. Subject has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in 
another clinical study involving an IP or investigational device during the course of this study
11. Subject is unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the Investigator
For non-commercial use only

BAX 802
Page 9 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
STATISTICAL ANALYSIS
Sample Size Calculation
The sample size of approximately 12 surgeries/procedures in 12 evaluable male subjects (at least 5 major 
surgeries/procedures in 5 evaluable subjects), as defined in the protocol, was chosen to provide sufficient 
evidence of safety and effectiveness for this indication and is not based on statistical considerations. 
Evaluable subjects are defined as subjects who met all study entry criteria and who had at least 
1 hemostatic efficacy assessment.
Planned Statistical Analysis
Analysis Sets
The safety analysis set (SAS) will be comprised of all subjects who received any amount of BAX 802. The 
full analysis set (FAS) will be comprised of all surgeries with at least 1 available hemostatic assessment. 
The per-protocol analysis set (PPAS) will be comprised of all surgeries with evaluable ratings for all 
3 perioperative hemostatic efficacy assessments, whose subjects met all study entry criteria and had no 
major protocol violations that might impact hemostatic efficacy assessments.
Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy assessed 
intraoperatively and postoperatively by the surgeon at postoperative Day 1 (postoperative period, i.e., from 
end of surgery to 24 ±6 hours post-surgery) and perioperatively at 24 to 72 hours after the last perioperative 
treatment dose of BAX 802 is administered or discharge (whichever is earlier) by the surgeon and by the 
Investigator, and will be the sum of intraoperative, postoperative, and perioperative GHEA scores rated 
“excellent”, “good”, “fair” or “none”.
If discharge is delayed for a reason other than surgery related bleeding (e.g., pneumonia), an assessment at 
24 to 78 hours after last perioperative treatment dose of BAX 802 will ensure that the overall perioperative 
assessment is completed close to the last administered study drug dose. Wherever possible (except for 
intraoperative assessment), bleeding should be assessed by both operating surgeon and Investigator. To 
achieve the hemostatic efficacy success criteria, the study needs to achieve a ≥70% rate of hemostatic 
efficacy assessments with an “excellent” or “good” outcome in at least 12 procedures.
Due to the possibility of a subject undergoing multiple surgeries, the statistical analysis of the primary 
outcome measure will be reported on the by-surgery level (i.e., not by the number of subjects). In cases 
where two or more surgical procedures are performed in the same intraoperative settings (under the same 
anesthesia, e.g., bilateral knee replacement) the surgery will be counted as one surgery. Blood loss 
assessment from those surgeries will be assessed as one. In the event that the subject is planning to have 
additional surgery in the future, the subject will need to complete the study and be re-screened again (if 
> 3 months from the screening) to ensure that they continue to meet the eligibility criteria.
Point estimates and corresponding 2-sided exact Clopper-Pearson confidence intervals (CIs) at the 95% 
confidence level will be calculated for the rate of hemostatic efficacy assessments with excellent/good 
outcome for descriptive purposes.
For non-commercial use only

BAX 802
Page 10 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The proportion of all surgeries and of all major surgeries with hemostatic success will be reported along 
with exact 95% CIs. A treatment success will be defined as a rating of excellent or good.
The primary efficacy analysis will be based on the FAS population. As a supportive analysis, the same 
calculations will also be carried out on the PPAS population.
A sensitivity analysis based on the first surgery will be performed if more than 20% of subjects have 
multiple surgeries.
Any blood loss which is considered as unrelated bleeding (defined as any bleeding occurring at a different 
anatomical site other than the surgery site during the postoperative period) will not be taken into account 
for while making assessment of hemostatic efficacy for the primary efficacy measure.
Secondary Outcome Measures
Secondary hemostatic efficacy analysis:
Secondary outcome measures will be reported at the surgery level rather than the subject level. Descriptive 
statistics will be used to summarize the actual blood loss and transfusion requirements. The proportion of 
major surgeries with good or excellent hemostatic score together with its 2-sided 95% CI will be reported
for descriptive purposes. 
The summary of average daily and total weight-adjusted doses (average through postoperative 24 to 
72 hours after last perioperative treatment dose of BAX 802 or discharge [whichever is earlier]) of 
BAX 802 per subject as well as the occurrence of bleeding episodes will be provided using descriptive 
statistics. 
For unrelated bleeding episodes in the postoperative period, descriptive statistics will be used to summarize 
the overall hemostatic efficacy rating at 24 ±2 hours after initiation of treatment and at resolution of bleed
(if not resolved within 24 hours). The secondary efficacy analysis will be performed on the FAS only. 
Separate descriptive summaries of average daily and total weight-adjusted doses required to treat unrelated 
bleeding episodes and will be provided.
Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will 
be summarized by presenting the number and proportion of subjects having any AE, having an AE in each 
system organ class, and having each individual AE as reported by preferred term. In the summaries, AEs 
will be counted only once per patient. If a patient reports the same AE more than once, it will be counted 
with its worst severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be tabulated. In addition, the 
number of subjects who experienced AEs related to IP and the number of IP related AEs will be tabulated 
and subcategorized for thrombo-embolic events, inhibitory and total binding antibodies (IgG and IgM) to 
rpFVIII and hFVIII, and binding antibodies to BHK proteins.
For non-commercial use only

BAX 802
Page 11 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
An overview table for AEs will be provided, presenting the number of AEs, the number of subjects with 
AEs and the corresponding percent of subjects in total, and by seriousness and relationship to study 
treatment. An additional summary table will present the total number of (mild, moderate, severe) AEs by 
system organ class and preferred term with relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. Descriptive 
statistics of changes from baseline (prior to BAX 802 loading dose before the surgery) by study visits will 
also be presented.
A frequency table of results of categorical laboratory parameters will be produced. Furthermore, laboratory 
abnormalities will be analyzed by shift tables where each subject will be counted only once with the worst 
grade in the summary tables.
Vital signs assessments as well as the corresponding changes from baseline will be summarized 
descriptively at each scheduled or unscheduled assessment.
For non-commercial use only

BAX 802
Page 12 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
4. TABLE OF CONTENTS
1. STUDY PERSONNEL.................................................................................................. 2
1.1 Authorized Representative (Signatory) / Responsible Party .............................. 2
1.2 Study Organization................................................................................................. 2
2. SERIOUS ADVERSE EVENT REPORTING........................................................... 3
3. SYNOPSIS..................................................................................................................... 4
4. TABLE OF CONTENTS ........................................................................................... 12
5. LIST OF ABBREVIATIONS .................................................................................... 17
6. BACKGROUND INFORMATION .......................................................................... 19
6.1 Description of Investigational Product ............................................................... 19
6.2 Clinical Condition/Indication .............................................................................. 19
6.3 Population to be Studied ...................................................................................... 21
6.4 Findings from Nonclinical and Clinical Studies................................................. 21
6.4.1 Finding from Nonclinical Studies................................................................. 21
6.4.2 Findings from Clinical Studies ..................................................................... 22
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 25
6.6 Compliance Statement.......................................................................................... 26
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 27
7.1 Study Purpose ....................................................................................................... 27
7.2 Primary Objective................................................................................................. 27
7.3 Secondary Objectives ........................................................................................... 27
7.4 Exploratory Objectives......................................................................................... 28
8. STUDY DESIGN......................................................................................................... 29
8.1 Brief Summary...................................................................................................... 29
8.2 Overall Study Design............................................................................................ 29
8.2.1 Types of Interventions................................................................................... 29
8.2.1.1 Major Surgeries ...................................................................................... 30
8.2.1.2 Minor Surgeries ...................................................................................... 30
8.2.2 Dose Selection Rationale ............................................................................... 31
8.3 Duration of Study Period(s) and Subject Participation .................................... 33
8.4 Outcome Measures ............................................................................................... 33
8.4.1 Primary Outcome Measure........................................................................... 33
For non-commercial use only

BAX 802
Page 13 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2 Secondary Outcome Measures ..................................................................... 36
8.4.2.1 Efficacy .................................................................................................... 36
8.4.2.2 Safety........................................................................................................ 37
8.4.3 Exploratory Outcome Measures................................................................... 37
8.5 Randomization and Blinding............................................................................... 37
8.6 Study Stopping Rules............................................................................................ 38
8.7 Investigational Product(s) .................................................................................... 38
8.7.1 Packaging, Labeling, and Storage................................................................ 38
8.7.2 Reconstitution and Administration.............................................................. 39
8.7.3 Description of Treatment.............................................................................. 40
8.7.3.1 FVIII Maintenance Plan ........................................................................ 40
8.7.3.2 Perioperative Dosing .............................................................................. 40
8.7.3.3 Dosing Schedule and Requirements...................................................... 40
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics .................................... 45
8.7.5 Investigational Product Accountability ....................................................... 46
8.8 Source Data ........................................................................................................... 46
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 47
9.1 Inclusion Criteria.................................................................................................. 47
9.2 Exclusion Criteria................................................................................................. 47
9.3 Withdrawal and Discontinuation ........................................................................ 48
10. STUDY PROCEDURES .......................................................................................... 49
10.1 Informed Consent ............................................................................................... 49
10.2 Subject Identification Code................................................................................ 49
10.3 Screening and Study Visits................................................................................. 49
10.4 Study Periods....................................................................................................... 50
10.4.1 Discharge/End of Study Visit...................................................................... 50
10.4.2 Antibody Testing Visit................................................................................. 50
10.4.3 Unscheduled Visit ........................................................................................ 50
10.5 Medications and Non-Drug Therapies.............................................................. 51
10.6 Rescue Medications............................................................................................. 52
10.7 Subject Completion/Discontinuation ................................................................ 52
10.8 Procedures for Monitoring Subject Compliance ............................................. 53
11. ASSESSMENT OF EFFICACY.............................................................................. 54
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score 54
11.2 Secondary Efficacy Endpoints........................................................................... 54
11.2.1 Blood Loss..................................................................................................... 54
11.2.2 Blood Transfusions ...................................................................................... 55
11.2.3 Bleeding Episodes ........................................................................................ 55
11.2.4 BAX 802 Administration............................................................................. 56
For non-commercial use only

BAX 802
Page 14 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical Site 
Bleeding Episodes.......................................................................................... 56
11.3 Factor VIII Activity............................................................................................ 57
11.3.1 Blood Sampling and Processing for FVIII Analysis................................. 58
12. ASSESSMENT OF SAFETY................................................................................... 59
12.1 Adverse Events.................................................................................................... 59
12.1.1 Definitions..................................................................................................... 59
12.1.1.1 Serious Adverse Event.......................................................................... 59
12.1.1.2 Suspected Unexpected Serious Adverse Reaction ............................. 60
12.1.1.3 Non-Serious Adverse Event ................................................................. 61
12.1.1.4 Unexpected Adverse Events................................................................. 61
12.1.1.5 Preexisting Diseases.............................................................................. 61
12.1.2 Assessment of Adverse Events.................................................................... 61
12.1.2.1 Severity .................................................................................................. 63
12.1.2.2 Causality................................................................................................ 63
12.1.2.3 Safety Reporting ................................................................................... 64
12.2 Urgent Safety Measures ..................................................................................... 65
12.3 Untoward Medical Occurrences........................................................................ 66
12.4 Non-Medical Complaints ................................................................................... 66
12.5 Medical, Medication, and Non-Drug Therapy History................................... 67
12.6 Physical Examinations........................................................................................ 67
12.7 Clinical Laboratory Parameters........................................................................ 68
12.7.1 Hematology, Clinical Chemistry, and Urinalysis...................................... 68
12.7.2 Viral Serology............................................................................................... 69
12.7.3 Immunogenicity ........................................................................................... 69
12.7.4 Assessment of Laboratory Values .............................................................. 70
12.7.4.1 Assessment of Abnormal Laboratory Values..................................... 70
12.7.5 Backup Samples and Biobanking............................................................... 70
12.8 Vital Signs............................................................................................................ 70
12.9 Karnofsky Performance Test............................................................................. 71
12.10 Special Treatment Considerations .................................................................. 71
13. STATISTICS............................................................................................................. 73
13.1 Sample Size and Power Calculations ................................................................ 73
13.2 Analysis Sets ........................................................................................................ 73
13.2.1 Safety Analysis Set....................................................................................... 73
13.2.2 Efficacy Datasets.......................................................................................... 73
13.2.2.1 Full Analysis Set.................................................................................... 73
13.2.2.2 Per-Protocol Analysis Set..................................................................... 73
13.3 Handling of Missing, Unused, and Spurious Data........................................... 73
13.4 Methods of Analysis............................................................................................ 74
13.4.1 Primary Outcome Measure......................................................................... 74
13.4.2 Secondary Outcome Measures ................................................................... 75
For non-commercial use only

BAX 802
Page 15 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.2.1 Secondary Hemostatic Efficacy Analysis............................................ 75
13.4.2.2 Safety Analysis ...................................................................................... 76
13.4.1 Exploratory Outcome Measures................................................................. 77
13.5 Planned Interim Analysis of the Study ............................................................. 77
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 77
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 78
15.1 Investigator’s Responsibility.............................................................................. 78
15.1.1 Investigator Report and Final Clinical Study Report.............................. 78
15.2 Training ............................................................................................................... 78
15.3 Monitoring........................................................................................................... 78
15.4 Safety Monitoring ............................................................................................... 78
15.5 Auditing ............................................................................................................... 79
15.6 Non-Compliance with the Protocol ................................................................... 79
15.7 Laboratory and Reader Standardization ......................................................... 79
16. ETHICS ..................................................................................................................... 80
16.1 Subject Privacy ................................................................................................... 80
16.2 Ethics Committee and Regulatory Authorities................................................ 80
16.3 Informed Consent ............................................................................................... 80
17. DATA HANDLING AND RECORD KEEPING................................................... 82
17.1 Confidentiality Policy ......................................................................................... 82
17.2 Study Documentation and Case Report Forms ............................................... 82
17.3 Document and Data Retention........................................................................... 82
18. FINANCING AND INSURANCE........................................................................... 83
19. PUBLICATION POLICY........................................................................................ 83
20. SUPPLEMENTS....................................................................................................... 84
20.1 Procedures per Study Period............................................................................. 84
20.2 Study Flow Chart................................................................................................ 89
20.3 Schedule of Study Procedures and Assessments.............................................. 90
20.4 Clinical Laboratory Assessments ...................................................................... 93
20.5 Global Efficacy Assessments Scores.................................................................. 96
20.6 Definitions............................................................................................................ 97
20.6.1 Joint Bleeds................................................................................................... 97
20.6.2 Muscle Bleeds............................................................................................... 97
For non-commercial use only

BAX 802
Page 16 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES.......................................................................................................... 98
22. SUMMARY OF CHANGES.................................................................................. 101
INVESTIGATOR ACKNOWLEDGEMENT............................................................ 123
Tables
Table 1: Global Hemostatic Efficacy Assessment (GHEA)............................................. 34
Table 2: Intraoperative Efficacy Assessment Scale (GHEA1)......................................... 35
Table 3: Postoperative Efficacy Assessment Scale (GHEA2) (Postoperative Day 1)...... 35
Table 4: Overall Perioperative Efficacy Assessment Scale (GHEA3) (at Discharge or 
Within 24 to 72 hours after the last perioperative treatment dose of BAX 802 
[whichever is earlier])............................................................................................... 36
Table 5: Dosing for Perioperative Management............................................................... 41
Table 6: BAX 802 Treatment Guidelines for Unrelated/Surgical Site Bleeding Episodes
................................................................................................................................... 44
Table 7: Efficacy Rating Scale for Treatment of Unrelated/Surgical Site Bleeding 
Episodes .................................................................................................................... 57
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502 .............. 84
Table 9: Schedule of Study Procedures and Assessments................................................ 90
Table 10: Clinical Laboratory Assessments ..................................................................... 93
Table 11: Combinations of Individual Efficacy Assessments (GHEA1, GHEA2, and 
GHEA3) and GHEA Score ....................................................................................... 96
Figures
Figure 1: Postoperative FVIII Monitoring........................................................................ 43
Figure 2: Visit Schedule.................................................................................................... 89
For non-commercial use only

BAX 802
Page 17 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
5. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
AHA
acquired hemophilia A
AICC
anti-inhibitor coagulant complex 
ALT
alanine aminotransferase
aPCC
activated prothrombin complex concentrate 
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
B19V
parvovirus B19
BHK
baby hamster kidney 
BU
Bethesda units
CI
confidence interval
CHA
Congenital Hemophilia A
CRF
case report form
CTA
Clinical Trial Agreement
DIC
disseminated intravascular coagulation
DSMB
data safety monitoring board
EBL
estimated blood loss
EC
Ethics Committee
ELISA
enzyme-linked immunosorbent assay
EU
European Union
FAS
full analysis set 
FDA
(United States) Food and Drug Administration
FVIII
Factor VIII
GCP
Good Clinical Practice
GHEA
Global Hemostatic Efficacy Assessment 
HAV
hepatitis A virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCT
hematocrit
HCV
hepatitis C virus
HEV
hepatitis E virus
hFVIII
human factor VIII 
HIV
human immunodeficiency virus
For non-commercial use only

BAX 802
Page 18 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Abbreviation
Definition
ICF
informed consent form 
ICH
International Council for Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use
IgG
immunoglobulin G
IgM
immunoglobulin M
IP
investigational product
IPC
intermittent pneumatic compression 
IRB
Institutional Review Board
ITI
immune tolerance induction
ITT
intent-to-treat 
LMWH
low molecular weight heparin 
MedDRA
Medical Dictionary for Regulatory Activities 
NMC
Non-medical complaint
OR
operating room
PCR
polymerase chain reaction 
pFVIII
porcine factor VIII 
PK
pharmacokinetics
PPAS
per protocol (analysis set)
PT/INR
prothrombin time/international normalized ratio 
PV
plasma volume
rhFVIII
recombinant human factor VIII 
rpFVIII
recombinant porcine factor VIII 
RSI
Reference Safety Information
SAE
serious adverse event
SAER
serious adverse event report
SAP
statistical analysis plan 
SAS
safety analysis set 
SIC
subject identification code
SOC
standard of care
SUSAR
Suspected Unexpected Serious Adverse Reaction
TGA
thrombin generation assays 
U
unit(s)
ULN
upper limit of normal
US
United States
US CFR
US Code of Federal Regulations 
VIIa
activated factor VII 
WFH
World Federation of Hemophilia
For non-commercial use only

BAX 802
Page 19 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
The investigational product (IP), BAX 802, is a recombinant form of porcine factor VIII 
(rpFVIII) from which the B domain has been deleted. Deletion of the B domain does not 
affect the safety or efficacy of this recombinant form of human factor VIII (rhFVIII) in 
the treatment of hemophilia A. BAX 802 (rpFVIII) is being developed for the 
perioperative management of hemostasis in subjects with congenital hemophilia A 
(CHA) with inhibitors to human factor VIII (hFVIII) undergoing surgical or other 
invasive procedures. This rpFVIII was approved by the United States Food and Drug 
Administration (FDA) in 2014 for the treatment of bleeding episodes in adults with 
acquired hemophilia A (AHA; non hemophilia subjects developing spontaneous 
autoantibody inhibitors to hFVIII) under the trade name OBIZUR®.
6.2 Clinical Condition/Indication
Congenital hemophilia A is a congenital bleeding disorder caused by a deficiency or 
complete absence of coagulation factor VIII (FVIII) 1 and is referred to as CHA in order 
to differentiate it from AHA, which is a rare autoimmune disease with different bleeding 
patterns caused by immunoglobulin G antibodies that bind to specific domains on the 
FVIII molecule, in a person with a negative personal or family history of a 
coagulopathy.2
Overall, CHA accounts for about 80% of hemophiliacs. It affects all ethnic populations 
and its prevalence varies among different countries, but is estimated at a rate of 3 to 
20 cases per 100,000 population. The World Federation of Hemophilia (WFH) has 
estimated the total number of hemophilia cases at about 500,000 worldwide, of which 
one-third are diagnosed. The tendency to bleed in these subjects correlates with the 
plasma level of FVIII. This lifelong disorder has 3 clinical phenotypes (severe, moderate, 
and mild) that correlate with FVIII levels in plasma (< 1%, 1 to 5%, and 5 to 40%, 
respectively).3
Subjects with hemophilia A typically develop recurrent bleeding episodes. The most 
effective approach for treatment of acute bleeding episodes in subjects with hemophilia A 
is hFVIII replacement therapy.4,5 However, a major complication in the treatment of 
subjects with hemophilia A is the development of neutralizing antibodies (inhibitors) to 
hFVIII, which impair the efficacy of replacement therapy with hFVIII concentrates. 
Inhibitor development occurs more frequently among patients with severe or moderately 
severe hemophilia, and approximately 30% of patients with severe CHA develop 
inhibitors. In CHA patients with high-responding inhibitors, standard replacement 
For non-commercial use only

BAX 802
Page 20 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
therapy with FVIII concentrates is usually ineffective, resulting in poor control of 
hemorrhagic episodes. This, in turn, increases the risk of morbidity, mortality, orthopedic 
complications and disability, as well as reduced quality of life, compared with patients 
without inhibitors.6 Patients with CHA with inhibitors are also at risk of perioperative 
bleeding complications, since replacement of the missing coagulation factor is 
ineffective, presenting a therapeutic challenge in elective or emergency surgery.7
Currently Available Treatments and Unmet Medical Need
In CHA patients with transient, low-responding, and/or low-titers (< 5 Bethesda units 
[BU]/mL) inhibitors, increased doses of FVIII may be sufficient to overcome the 
inhibitor and provide hemostasis. In CHA patients with high-responding inhibitors 
(> 5 BU/mL), standard replacement therapy with FVIII concentrates is usually 
ineffective, resulting in poor control of hemorrhagic episodes. 
Alternative therapies are required for subjects with inhibitors who no longer respond to 
hFVIII replacement therapy. Recombinant activated factor VII (rFVIIa, NovoSeven®) 
and FEIBA (FVIII inhibitor bypassing activity; anti-inhibitor coagulant complex [AICC]) 
bypass the normal coagulation cascade and hence the FVIII inhibitors, and are therefore 
referred to as bypassing agents. Although these agents are able to manage bleeding in the 
presence of inhibitors, they do not attempt to restore the normal pathways of hemostasis, 
but instead boost thrombin generation despite a lack of platelet-surface FVIIIa–FIXa 
(‘tenase’) activity.6 The measurement of levels of factor VIIa in the subject’s plasma 
cannot be used as a clinically relevant surrogate marker and does not correlate with 
clinical outcome. Without an adequate biomarker, the dosage and treatment schedule 
cannot be clearly defined.8 In addition, the response to rFVIIa treatment may be 
inconsistent both from subject to subject and between different bleeds in the same 
subject. Because FEIBA is a human plasma fraction containing several coagulation 
factors, it has the potential to transmit human pathogens and may also cause 
thromboembolic events. Since the plasma fraction also contains hFVIII, it has been 
associated with a rise in hFVIII antibodies in approximately 20% of subjects.9
Moreover, as with rFVIIa, there is no validated biomarker that correlates with the clinical 
outcome with FEIBA treatment, although both thrombin generation assays (TGA) and 
whole blood viscoelastic assays have been evaluated for this purpose with some 
success.10
For non-commercial use only

BAX 802
Page 21 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The ultimate goal of treatment for these patients is eradication of the inhibitor through 
immune tolerance induction (ITI), which involves frequent and long-term administration 
of factor concentrates in an attempt to build tolerance in the immune system to FVIII or 
factor IX, and thus restore responsiveness to factor replacement therapy. However, 
ITI fails in approximately 30% of inhibitor patients with CHA.6
There is therefore a clinical need for an effective hemostatic agent for use in subjects with 
CHA who have inhibitors to hFVIII, and which allows monitoring of hemostatic efficacy 
based upon measurement of plasma FVIII activity levels, thus facilitating early 
determination of clinical benefit and the patient’s clinical status.
6.3 Population to be Studied
The study population will comprise of at least 12 procedures in 12 evaluable male 
subjects with CHA with inhibitors to hFVIII undergoing major or minor elective surgical, 
dental, or other invasive procedures (of which no more than 20% can be dental or other 
non-operative invasive procedures). Of 12 evaluable subjects, at least 2 will be 
adolescents (≥ 12 to < 18 years old), and in total there will be at least 5 major surgeries in 
5 evaluable subjects. Subjects will be considered to be eligible provided that they satisfy 
all of the inclusion criteria listed in Section 9.1 and none of the exclusion criteria listed in 
Section 9.2. In order to evaluate the activity of the product with respect to high-titer or 
high-responding inhibitors to hFVIII, at least 3 adult subjects with screening anti-hFVIII 
inhibitor titers of ≥ 5 BU will be enrolled in the study.
6.4 Findings from Nonclinical and Clinical Studies
6.4.1 Finding from Nonclinical Studies
Nonclinical studies were performed with rpFVIII to demonstrate hemostatic activity in 
2 animal models of hemophilia A (mice and dogs), local and systemic tolerance in a 
range of doses in single or repeat dose toxicology studies in monkeys, pharmacokinetics 
(PK) in dogs and monkeys, and immunogenicity in mice and monkeys.
Compatibility with the usual injection materials (needles, plastic syringes, and butterfly 
infusion needles with tubing) has been demonstrated. Studies in monkeys demonstrated 
the tolerability of repeated single daily injections of rpFVIII at doses up to 1000 U/kg, 
with injections at each dose level given once daily for 7 days. In 2 animal models of 
hemophilia A (mice and dogs), the hemostatic activity of rpFVIII was studied in 
comparison with Hyate:C. The rpFVIII was found to be efficacious in a dose-related 
fashion in controlling the bleeding associated with a standardized hemorrhagic insult. No 
animal studied was observed to have had an acute reaction to the injection of rpFVIII.
For non-commercial use only

BAX 802
Page 22 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.4.2 Findings from Clinical Studies
The safety and efficacy of rpFVIII was explored in 4 clinical trials prior to marketing 
approval:

OBI-1-101 (N=9): a Phase 1, multicenter, randomized, double-blinded, double-
dummy, parallel-group, comparison of the safety, tolerance, and PK study of 
rpFVIII versus Hyate:C was conducted.11

OBI-1-201 (N=9): a Phase 2, prospective, open-label, non-comparative study was 
conducted to assess the hemostatic activity of rpFVIII. Eligible subjects had a 
clinical diagnosis of hemophilia A with inhibitors to hFVIII, an anti-pFVIII
inhibitor antibody titer < 20 BU at screening, and an uncomplicated joint or soft 
tissue bleed, or other non-life threatening and non-limb threatening bleeding 
episode.12

OBI-1-301 (N=29): a multicenter, open-label, single-cohort, prospective, Phase 2/3
study of rpFVIII in subjects with acquired hemophilia to determine the hemostatic 
efficacy and safety of rpFVIII in the control of serious bleeding episodes.13

OBI-1-302 (terminated at N=1): a prospective, non-randomized, open-label study 
designed to assess treatment of serious bleeding episodes with rpFVIII in subjects 
with CHA who had developed anti-hFVIII inhibitors; this study was terminated by 
the sponsor after 1 subject was treated for administrative reasons, not due to safety 
or lack of efficacy concerns.
In all clinical studies, rpFVIII was generally well tolerated. There were no drug-related 
AEs reported in subjects who received rpFVIII in the Phase 1 study. One subject in the 
Phase 2 study (OBI-1-201) experienced pruritus (that resolved with diphenhydramine) 
that was possibly related to study drug. This AE occurred during the first bleeding 
episode, but the subject did not have a reaction during a second rpFVIII treated bleeding 
episode. In the Phase 1 and Phase 2 studies, no AEs led to treatment interruption, 
discontinuation from the study, or death. Vital signs, laboratory values, medical history 
and physical examination findings were within normal parameters for both studies and 
raised no safety concerns. 
In the Phase 2 study (OBI-1-201), the intent-to-treat (ITT) population consisted of 9 male 
subjects with CHA and with an inhibitor antibody to hFVIII. Six of the subjects (67%) 
were black and 3 subjects (33%) were Caucasian. The mean age of the subject population 
was 23.7 years (range: 14 to 34). The primary efficacy objective of the study was 
to evaluate the hemostatic efficacy of rpFVIII in the treatment of non-life/non-limb 
threatening bleeds in subjects with CHA and inhibitors.
For non-commercial use only

BAX 802
Page 23 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
A total of 25 bleeds in 9 subjects were treated with rpFVIII and all bleeds were 
successfully controlled with 8 or less injections of rpFVIII. The median number of 
rpFVIII injections administered per bleeding episode was 1.0 (range: 1 to 8) and the 
median time from bleeding onset to treatment was 5.67 hours (range: 1.5 to 20.0). Across 
all bleeding episodes the median total dose of rpFVIII per bleeding episode was 
224.1 U/kg (range: 50.0 to 1066.4). The median initial Treatment Dose (including the 
loading dose if applicable), was 159 U/kg (range: 50 to 576) and resulted in a median 
increase of FVIII plasma level of 16 % with the 1-stage clotting assay (range: 0.5% to 
427%) and a median increase of 17% with the chromogenic assay (range: 0% to 248%). 
Twenty of the 25 (80%) bleeds were controlled within 6 hours having been administered 
1 Treatment Dose of rpFVIII. For those 20 bleeds controlled with 1 Treatment Dose 
(including the loading dose if applicable), the median dose was 200.8 U/kg. The rpFVIII 
was well tolerated and of the reported AEs (n=61) only 18 AEs were considered 
treatment emergent. Two subjects reported an AE that was possibly related to study drug. 
One AE of itching/pruritus during the first bleeding episode but without reaction during a 
second rpFVIII treated bleeding episode. The second AE was a report of increased ALT 
and aspartate aminotransferase (AST), possibly associated with a confirmed hepatitis C 
infection, while it was uncertain whether the corresponding blood sample was taken 
before or after rpFVIII administration. Three subjects suffered treatment emergent SAEs 
but none were considered related to study drug. No reported AE led to treatment 
interruption, discontinuation from the study or death. Eight out of 9 (8/9, 89%) subjects 
developed anti-pFVIII antibodies following exposure to rpFVIII. In subjects who
received repeated rpFVIII treatment, higher anti-pFVIII titers did not affect efficacy or 
safety and no increase in AEs or bleeding episodes were reported in the subjects with the 
highest titers. Regardless of the observed anti-pFVIII titers at pre-treatment or the 
obtained FVIII recovery values after treatment initiation, all bleeding episodes were 
successfully controlled. Analyses of baby hamster kidney (BHK; host cell line) antibody 
levels indicated that no subjects produced detectable levels of antibodies against BHK.
In the prospective, open-label trial (OBI-1-301), the efficacy of rpFVIII for the treatment
of serious bleeding episodes in subjects with AHA was investigated. The trial was 
conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects diagnosed with 
AHA, having auto-immune inhibitory antibodies to hFVIII, and experiencing serious 
bleeding episodes that required hospitalization. Subjects with a prior history of bleeding 
disorders other than AHA, anti-pFVIII antibody titer > 20 BU, or in whom the bleeding 
episode was judged likely to resolve on its own, were excluded. One subject was 
considered evaluable at study entry; however, it was later determined that this subject did 
not have AHA, leaving 28 subjects evaluable for efficacy. Of the 28 subjects evaluable 
for efficacy, all subjects had a positive response to treatment for the initial bleeding 
For non-commercial use only

BAX 802
Page 24 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
episodes at 24 hours after dosing. A positive response was observed in 95% (19/20) of 
subjects evaluated at 8 hours and 100% (18/18) at 16 hours. In addition to response to 
treatment, the overall treatment success was determined by the Investigator based on 
his/her ability to discontinue or reduce the dose and/or dosing frequency of rpFVIII. A 
total of 24/28 subjects (86%) had successful treatment of the initial bleeding episode. Of 
those subjects treated with rpFVIII as first-line therapy, defined as no immediate previous 
use of anti-hemorrhagic agents prior to the first rpFVIII treatment, 16/17 subjects (94%) 
had eventual treatment success reported. Eleven subjects were reported to have received 
anti-hemorrhagics (eg, rFVIIa, activated prothrombin-complex concentrate, and 
tranexamic acid) prior to first treatment with rpFVIII. Of these 11 subjects, 8 had 
eventual successful treatment (73%). No related serious adverse reactions occurred. Non-
serious AEs related to treatment were noted and assessed by the Investigator in 6/29 
subjects (20.7%). One subject had mild tachycardia, hypotension and constipation. One 
subject had 2 instances of mild peripherally inserted central catheter (PICC) line 
occlusion. One subject had a mild hypofibrogenemia and 1 subject had moderate mental 
status changes. All of these adverse effects completely resolved. Two subjects developed 
anti- pFVIII inhibitors after infusion of study drug (range 8 to 51 BU) and were 
discontinued from treatment; however both subjects had a positive response to treatment 
at the 24-hour primary endpoint assessment. An investigation was conducted by the 
sponsor and, in summary, the 2 incidences of anti-pFVIII inhibitors were considered 
related to rpFVIII treatment, while the other non-serious treatment-related adverse events 
were considered as unlikely to be related to rpFVIII. Anti-pFVIII inhibitors were detected 
prior to infusion in 10/29 patients (range 0.8 to 29 BU). All of these subjects had a 
positive response at 24 hours post-rpFVIII first infusion. No anti-BHK antibodies were 
observed in any of the 29 treated subjects.
At the time of OBIZUR® marketing approval, the clinical trial data indicated that rpFVIII 
was well tolerated and had demonstrated effectiveness in the control of bleeding in study 
subjects. Cumulatively (patient exposure from 01 Oct 2014 through 31 Oct 2016), 
approximately 16,424,000 units (U) of OBIZUR® were sold worldwide. Median (range) 
treatment dose per bleeding episode was 94,500 (35,256 to 182,700), and the estimated 
number of patient-years worldwide to OBIZUR® was approximately 347.6 (179.8 to 
931.6). As of 11 Nov 2016, there have been 20 post-marketing serious case reports with 
36 AEs. No adverse reactions other than those observed in clinical trials have been 
observed in the post marketing setting. The reports were consistent with the known safety 
profile of OBIZUR®.i
                                                
i Obizur Periodic Safety Update Report/Periodic Benefit-Risk Evaluation Report (PSUR/PBRER), 
reporting interval 12 MAY 2016 to 11 NOV 2016.
For non-commercial use only

BAX 802
Page 25 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Porcine FVIII (Hyate:C), derived from porcine plasma, had been used successfully 
starting in the 1980s to achieve hemostasis in the presence of anti-hFVIII inhibitors, as 
the antibodies generally have low immunological cross-reactivity with pFVIII.14
However, the number of hemophilia A subjects who were appropriate candidates to 
receive Hyate:C was limited by the degree to which their anti-hFVIII antibodies 
cross-reacted with pFVIII and the presence of any anti-pFVIII inhibitors. While a median 
inhibitor cross-reactivity observed to porcine VIIIC was only 15%, an absent, 
intermediate, or brisk specific anti-porcine anamnestic response was observed in 29%, 
40%, and 31% of patients, respectively.15 The commercial production of Hyate:C was 
discontinued in 2005 due to problems with sourcing suitable porcine plasma, but not due 
to any safety or efficacy concerns. 
BAX 802 is a B-domain deleted rpFVIII glycoprotein which is being developed for the 
perioperative management of hemostasis in subjects with CHA with FVIII inhibitors 
undergoing surgical or other invasive procedures. B-domain deleted rpFVIII glycoprotein 
has been extensively studied. BAX 802 (as marketed OBIZUR®) is not currently 
indicated for the treatment of CHA.16
OBIZUR® was approved based on the safety and efficacy data from 28 subjects with 
AHA treated with B-domain deleted rpFVIII glycoprotein in the Phase 2/3 open-label 
clinical study OBI-1-301. The safety, hemostatic activity, and PK profile of B-domain 
deleted rpFVIII glycoprotein was also supported by results of an open-label Phase 2 study 
in patients with CHA with inhibitors (Clinical Study Report OBI-1-201), and a 
randomized Phase 1 study comparing B-domain deleted rpFVIII glycoprotein with a 
plasma-derived pFVIII (CSR OBI-1-101). 
The data supported the use of B-domain deleted rpFVIII glycoprotein to treat serious 
bleeding episodes in AHA patients (Section 6.4.2). It was demonstrated that B-domain 
deleted rpFVIII glycoprotein provides benefit to AHA patients who are unresponsive to 
alternative agents with an improved dosing algorithm. It was possible to monitor 
hemostatic efficacy based upon measurement of plasma FVIII activity levels, thus 
facilitating early determination of clinical benefit and the patient’s clinical status. An 
additional benefit to the patient was that it was possible to adjust the dose based on the 
FVIII levels rather than follow fixed dosing, ensuring that adequate doses were
administered to achieve hemostasis.
For non-commercial use only

BAX 802
Page 26 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The most frequently reported adverse reaction in patients with AHA was the development 
of inhibitors to pFVIII.16
Overall, efficacy and safety clinical data for OBIZUR supported a favorable benefit/risk 
determination for the proposed indication of treatment of bleeding episodes in adults with 
AHA.
These data support the investigation of efficacy and safety of BAX 802 in subjects with 
CHA with inhibitors undergoing surgical or other invasive procedures. 
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council 
for Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), 
Title 21 of the United States (US) Code of Federal Regulations (US CFR), the European 
Union (EU) Directives 2001/20/EC and 2005/28/EC, and applicable national and local 
regulatory requirements.
For non-commercial use only

BAX 802
Page 27 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to evaluate the efficacy and safety of BAX 802 in males with 
CHA with inhibitors who are undergoing major or minor elective surgical, dental, or 
other invasive procedures. 
7.2 Primary Objective
The primary objective of the study is to evaluate the perioperative hemostatic efficacy of 
BAX 802 in male subjects with CHA with inhibitors to hFVIII undergoing major or 
minor elective surgical, dental, or other invasive procedures as determined by the Global 
Hemostatic Efficacy Assessment (GHEA) score.
7.3 Secondary Objectives
The secondary objectives of the study are:
1.
To determine the safety of BAX 802 used in the perioperative setting by assessing:

The development of and change in titer of anti-pFVIII and anti-hFVIII 
antibodies (binding and neutralizing), and development of binding antibodies to 
BHK proteins

The occurrence of thrombo-embolic events and/or allergic reactions to 
BAX 802

The occurrence of AEs related to BAX 802

The occurrence of clinically significant changes in vital signs and routine 
laboratory parameters related to BAX 802
2.
To determine the intraoperative, postoperative, and overall perioperative blood loss, 
compared to the estimated volume of expected average and maximum blood loss in 
a comparable healthy individual as predicted preoperatively by the 
Investigator/surgeon
3.
To determine the proportion of major surgeries with good or excellent hemostatic 
score
4.
To determine the daily and total weight-adjusted administration of BAX 802 per 
subject
For non-commercial use only

BAX 802
Page 28 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7.4 Exploratory Objectives
The exploratory objectives of the study are:
 
 
 
 
 
 
For non-commercial use only

BAX 802
Page 29 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8. STUDY DESIGN
8.1 Brief Summary
This study is a Phase 3, prospective, single-arm, open-label, uncontrolled, multicenter 
study to evaluate the efficacy and safety of BAX 802 in at least 12 procedures in 
12 evaluable male subjects ≥12 to ≤75 years old with CHA with inhibitors to hFVIII 
who are undergoing major and minor surgical, dental or other invasive procedures. At 
least 5 of the procedures must be major surgeries in 5 evaluable subjects, of which no 
more than 20% can be dental or other non-operative invasive procedures (see 
Section 8.2.1), and at least 3 adult subjects with screening anti-hFVIII titers of ≥5 BU for 
inhibitors to human FVIII will be enrolled in the study. At least 2 adolescents (≥12 to 
< 18 years old) will be enrolled in the study.
8.2 Overall Study Design
The dose and frequency of BAX 802 during the preoperative, intraoperative, and 
postoperative periods should follow a proposed substitution plan provided by the 
Investigator to the medical monitor prior to surgery and adjusted based on regular FVIII 
activity measurements (see Section 8.7.3.1). The regimen will depend on the type of 
surgery performed and the intensity of the hemostatic challenge.
Elective surgical procedures will prospectively be defined as major or minor by the 
Investigator/surgeon and agreed with the medical director/designee, based on the protocol 
guidance and definitions and in consideration of each subject’s characteristics. 
Emergency surgeries are not in the scope of this study. Subjects may undergo more 
than 1 surgery or 2 parallel surgeries, such as bilateral knee replacement. For subjects 
undergoing multiple surgeries (other than parallel surgeries), the End of Study visit
should be completed for the first surgery and then subject needs to be re-screened
(Section 10.3) for the next surgery.
The study will be divided into 5 periods: Screening, Preoperative, Intraoperative, 
Postoperative, and End of study (Table 8). The study will be conducted at multiple sites 
in North America, Europe, and South Africa.
The overall study design is illustrated in Figure 2. 
8.2.1 Types of Interventions
Elective surgeries and other invasive procedures will prospectively be defined by the 
Investigator/surgeon as major or minor based on the definitions and examples provided in 
Section 8.2.1.1 and Section 8.2.1.2, respectively, taking into consideration each 
individual patient’s characteristics and agreement with the sponsor.
For non-commercial use only

BAX 802
Page 30 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.2.1.1 Major Surgeries
Major surgeries include surgeries that require moderate or deep sedation, general 
anesthesia, or major conduction blockade for patient comfort. This generally refers to 
major orthopedic (e.g., joint replacement), major abdominal, intracranial, cardiovascular, 
spinal and any other surgery which has a significant risk of large volume blood loss 
(> 500 mL) or blood loss into a confined anatomical space. Extraction of at least 3 teeth 
or extraction of the third molar are generally considered as major. Examples include:

bone fixation for fracture

hip and knee replacement (arthroplasty)

arthrodesis (joint fusion)

open synovectomy

osteotomy

liver biopsy

pseudotumor removal

hardware removal (plates and intramedullary nails)
Major surgeries/interventions are expected to require clinical surveillance or hospital 
treatment > 3 days after the surgery/intervention. 
8.2.1.2 Minor Surgeries
Minor surgeries include surgeries that can be safely and comfortably performed on a 
patient who has received local or topical anesthesia, without more than minimal 
preoperative medication or minimal preoperative medication or minimal intraoperative 
sedation. The estimated total blood loss should be < 500 mL and the likelihood of 
complications requiring hospitalization or prolonged hospitalization should be remote. It 
refers to interventions such as removal of skin lesions, arthroscopy, minor dental 
procedures or dental extractions. Examples include:

removal of skin lesions

minor dental procedures or dental extractions (except extraction of 3 or more teeth 
or third molar extraction)

placement and/or removal of central venous catheters

synoviorthesis and arthrocentesis
For non-commercial use only

BAX 802
Page 31 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

arthroscopy

nerve release

removal of osteophytes and small cysts 
Minor surgeries/interventions are expected to require clinical surveillance or hospital 
treatment ≤3 days after the surgery/intervention
8.2.2 Dose Selection Rationale
Background
This is a Phase 3, multicenter, single-arm, open-label study of the efficacy and safety of 
B-domain deleted rpFVIII (BAX 802) in the perioperative management of hemostasis in 
subjects with CHA who have inhibitors and are undergoing surgical or other invasive 
procedures. The rpFVIII temporarily replaces the inhibited FVIII that is needed for 
effective hemostasis in CHA patients who have developed inhibitors to hFVIII. The 
principle of using pFVIII is based on its low cross-reactivity with anti-hFVIII antibodies 
due to sequence variations between human and pFVIII in the A2 and C2 domains, the 
main targets of FVIII inhibitors. The rpFVIII concentrate is predicted to have an 
advantage over human-derived FVIII in CHA patients who have inhibitors since previous 
studies demonstrated that the antibodies have a median of only 15% cross-reactivity with 
plasma-derived pFVIII.17
Regulatory approval for rpFVIII for the treatment of bleeding episodes in adults with 
AHA was received for OBIZUR®; per the product label, the initial dose of OBIZUR® is 
200 U/kg, with subsequent dosing dependent on the location and severity of bleeding 
episode, target FVIII levels, and the patient’s clinical condition.16
Influence of Anti-pFVIII Inhibitor Titer on the Loading Dose
Anti-pFVIII inhibitors are neutralizing antibodies against pFVIII that neutralize the 
pFVIII, and thereby reduce its hemostasis effect. Anti-pFVIII inhibitors can be quantified 
in plasma by the Bethesda assay, which measures the ability of the patient’s plasma to 
neutralize exogenous pFVIII when incubated together.
The amount of BAX 802 required to neutralize the anti-pFVIII activity is factored in. 
A BU is defined as the amount of anti-pFVIII inhibitor in a plasma sample which will 
neutralize 50% of 1 unit of BAX 802 in normal plasma after 2 hour incubation at 37°C. 
For non-commercial use only

BAX 802
Page 32 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Only the inhibitor that is distributed in the plasma volume (PV) is initially available to 
neutralize the infused FVIII; PV is calculated using the following formula:
PV = Blood Volume × (1 – [hematocrit{HCT}%/100])
Normal blood volume is approximately 80 mL/kg for adults.
Therefore, PV = 80 × (1 – [HCT%/100]).
One BU of anti-pFVIII inhibitor will neutralize 50% of 1 unit of BAX 802; therefore, it is 
assumed that 0.5 U FVIII will be required for each 1 BU of inhibitor. The amount of 
BAX 802 required to neutralize the anti-pFVIII activity can be estimated using the 
following:
Body weight × 80(1 - [HCT%/100]) × 0.5 × anti-pFVIII inhibitor titer (BU) = 
body weight × 40(1-[HCT%/100]) × anti-pFVIII inhibitor titer (BU).
Proposed Dosing Regimen of BAX 802 in Study BAX 802 Surgery
The dosing scheme to be used in Study BAX 802 Surgery is presented in Section 8.7.3.3.
The loading dose of BAX 802 for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
[80 × body weight (kg)] + [body weight (kg) × 40(1-[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU)]
For example, for a 70 kg subject undergoing major surgery and having HCT 45% and 
anti-pFVIII inhibitor titer 3 BU, the loading dose of BAX 802 will is calculated as 
follows: 
[80 (70)] + [70 × 40(1-[45/100]) × 3] = 10,220 U
This dosing scheme should reasonably predict the loading dose before surgery that will 
provide sufficient FVIII levels needed for effective hemostasis.
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved (Table 5).
This dosing algorithm is essentially equivalent to that proposed by Kasper (2004) when 
using FVIII in the treatment of patients with low titer inhibitors.18
For non-commercial use only

BAX 802
Page 33 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study will be approximately 21 months from study initiation 
(i.e., first subject enrolled) to study completion (i.e., last subject, last visit). The 
recruitment period is expected to be approximately 18 months.  
The duration of subject participation depends on the nature of the invasive procedure: it 
will run from the signing of the informed consent until completion of the End of Study 
Visit at least 5 weeks post-surgery (end of surgery = Day 0), unless prematurely 
discontinued. Study completion is defined by the End of Study Visit after discharge.
8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is the proportion of all surgical, dental, or other invasive 
procedures with a “good” or “excellent” response as measured by GHEA score (Table 1), 
which is composed of 3 individual ratings:

GHEA1: Assessment of intraoperative (Day 0) hemostatic efficacy of BAX 802
performed by the operating surgeon (see Table 2) at the end of surgery

GHEA2: Assessment of postoperative hemostatic efficacy of BAX 802 at 
postoperative Day 1 (approximately 24 hours [± 6 hours] post-surgery) performed 
by the operating surgeon. If a patient is discharged < 24 hours following surgery, 
then the GHEA2 hemostatic efficacy assessment may require a return visit the 
following day (see Table 3)

GHEA3: Assessment of overall perioperative hemostatic efficacy of BAX 802 at
discharge or within 24 to 72 hours after the last perioperative treatment dose of 
BAX 802 (whichever is earlier), performed by the Investigator, and where possible, 
also by the operating surgeon. Assessment by both is strongly recommended. In 
cases where there are differing assessments, the Investigator’s assessment will be 
used (see Table 4)
Prior to the surgery, the surgeon/Investigator will predict the estimated volume (in mL) of 
the expected blood loss for the planned surgical intervention in a hemostatically normal 
individual of the same sex, age, and stature as the study subject, for intraoperative, 
postoperative, and overall perioperative time periods. Every effort should be made to 
predict the volume as precisely as possible, also taking into account, for example, the use 
of a tourniquet or placement of a postoperative drain and whether or not suction is used.
For non-commercial use only

BAX 802
Page 34 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The estimate will be for the intraoperative time period and from completion of the 
procedure until approximately 24 hours post-surgery and for the overall perioperative 
period (see Section 11.2.1).
The scores of each of the 3 individual ratings (GHEA1, GHEA2, and GHEA3) described 
above, will be added together to form a GHEA score according to Table 1. For a GHEA 
score of 7 to be rated “excellent” no individual assessment score should be less than 2 
(i.e., one individual assessment score must be 3 and the other two individual assessment 
scores must be 2). The only other option to achieve a GHEA score of 7 is for two
individual assessment scores of 3 and one individual assessment score of 1. Although this 
GHEA score will not qualify for a rating of “excellent,” the GHEA score will satisfy the 
definition of “good,” (with no individual assessment score less than 1). All possible 
combinations of the individual assessment scores and their related ratings are provided in 
Supplement Section 20.5. 
For surgeries with up to 2 missing hemostatic assessments that did not necessitate rescue 
therapies, the rating of “fair” will be imputed for these missing data. These surgeries will 
be included in the full analysis set (FAS). The assessment of primary outcome measure 
(GHEA score) should only account for the blood loss related to the surgery and exclude 
any blood loss which is considered as unrelated bleeding (defined as any bleeding 
occurring at a different anatomical site than the surgery site during the postoperative 
period, see Section 11.2.5).
Table 1: Global Hemostatic Efficacy Assessment (GHEA)
Assessment
GHEA Score
Excellent
7a to 9
(with no category scored < 2)
Good
5 to 7a
(with no category scored < 1)
Fair
3 to 4
(with no category scored < 1)
None
0 to 2 (or at least one category scored 0)
a For a GHEA score of 7 to be rated “excellent” (with no individual assessment scores less than 2), at least 
1 individual assessment score must be 3 and the other 2 individual assessment scores must be at least 2; 
otherwise a score of 7 is rated “good”.
For non-commercial use only

BAX 802
Page 35 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 2: Intraoperative Efficacy Assessment Scale (GHEA1)
At the end of surgery, the operating surgeon will assess the intraoperative hemostatic 
efficacy
Rating
Criteria
Score
Excellent
Intraoperative blood loss was less than or equal to that expected for the type of 
procedure performed in a non-hemophilic population (≤100%)
3
Good
Intraoperative blood loss was up to 50% more than expected for the type of 
procedure performed in a non-hemophilic population (101 to 150%)
2
Fair
Intraoperative blood loss was more than 50% of that expected for the type of 
procedure performed in a non-hemophilic population (> 150%)
1
None
Uncontrolled hemorrhage that was the result of inadequate therapeutic response 
despite proper dosing, necessitating rescue therapy or other FVIII products
0
Table 3: Postoperative Efficacy Assessment Scale (GHEA2) (Postoperative Day 1)
On postoperative Day 1 (24 ± 6 hours post-surgery), the operating surgeon will assess the 
postoperative hemostatic efficacy
Rating
Criteria
Score
Excellent
Postoperative blood loss was less than or equal to (≤100%) that expected for 
the type of procedure performed in a non-hemophilic population
3
Good
Postoperative blood loss was up to 50% more (101% to 150%) than expected 
for the type of procedure performed in a non-hemophilic population 
2
Fair
Postoperative blood loss was more than 50% (> 150%) of that expected for the 
type of procedure performed in a non-hemophilic population 
1
None
Significant postoperative bleeding that was the result of inadequate therapeutic 
response despite proper dosing, necessitating rescue therapy or other FVIII 
products
0
For non-commercial use only

BAX 802
Page 36 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 4: Overall Perioperative Efficacy Assessment Scale (GHEA3) (at Discharge or 
Within 24 to 72 hours after the last perioperative treatment dose of BAX 802 
[whichever is earlier])
At discharge or within 24 to 72 hours after the last perioperative treatment dose of BAX 802 
(whichever is earlier), the postoperative efficacy assessment will be performed by the 
Investigator, and where possible, also by the operating surgeon
Rating
Criteria
Score
Excellent
Overall perioperative blood loss was less than or equal to (≤100%) that 
expected for the type of procedure performed in a non-hemophilic population,
Required blood components for transfusions were less than or similar to that 
expected in non-hemophilic population
3
Good
Overall perioperative blood loss was up to 50% more (101% to 150%) than 
expected for the type of procedure performed in a non-hemophilic population
Required blood components for transfusions were less than or similar to that 
expected in non-hemophilic population
2
Fair
Overall perioperative blood loss was more than 50% of that expected for the 
type of procedure performed in a non-hemophilic population (> 150%)
Required blood components transfusions were greater than that expected in 
non-hemophilic population
1
None
Significant overall perioperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy or 
other FVIII products
Required blood components for transfusions were substantially greater than 
that expected in non-hemophilic population
0
Hemostatic efficacy success is defined as “excellent” or “good “outcome for ≥ 70% of 
hemostatic efficacy assessments.
8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy
1.
Intra- and post-operative blood loss compared to the estimated volume of expected 
average blood loss and expected maximum blood loss in a comparable healthy 
individual with similar demographic characteristics as predicted preoperatively by 
the Investigator/surgeon at the following time points:

Intraoperative, from start until the end of surgery

Postoperative Day 1, from end of surgery to approximately 24 hours 
(± 6 hours) after surgery

Overall perioperative at discharge or 24 to 72 hours after the last perioperative 
treatment dose of BAX 802 (whichever is earlier)
For non-commercial use only

BAX 802
Page 37 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2.
Proportion of major surgeries with good or excellent hemostatic score
3.
Daily and total weight-adjusted administration of BAX 802 per subject
4.
Amount of blood, red blood cells, platelets, and other blood products transfused
8.4.2.2 Safety
1.
Development of, and changes to, the titer of inhibitory and binding antibodies (IgG 
and IgM) to pFVIII
2.
Development of, and changes to, the titer of inhibitory and binding antibodies (IgG 
and IgM) to hFVIII
3.
Development of binding antibodies to BHK proteins
4.
Occurrence of thrombo-embolic events
5.
Incidence of severe allergic reactions (e.g., anaphylaxis)
6.
Incidence of other IP-related AEs
7.
Incidence of clinically significant changes in vital signs and routine laboratory 
parameters (hematology, clinical chemistry)
8.4.3 Exploratory Outcome Measures
 
 
 
 
 
8.5 Randomization and Blinding
This is a non-randomized, open-label, active treatment clinical study.
For non-commercial use only

BAX 802
Page 38 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.6 Study Stopping Rules
The study will be halted (enrollment stopped), pending further review by the external 
data safety monitoring board (DSMB) and sponsor, if 1 or more of the following criteria 
are met:
1.
Two or more subjects develop a severe anaphylactic reaction or any other serious 
adverse event (SAE) related to BAX 802 that would not be expected 
2.
The occurrence of Suspected Unexpected Serious Adverse Reaction (SUSAR)
3.
Other AEs that are deemed to pose unacceptable risks to subjects.
The study may be terminated, if 1 or more of the following criteria are met:
1.
The sponsor decides to terminate the study based upon DSMB recommendation or 
its own assessment of safety
2.
The sponsor decides to terminate the study at any time for administrative reasons.
8.7 Investigational Product(s)
The IP, BAX 802, is a recombinant purified form of rpFVIII from which the B domain 
has been deleted and replaced with a 24 amino acid linker. Recombinant pFVIII 
(BAX802) is expressed as a glycoprotein by a genetically engineered BHK cell line. 
The molecular weight of rpFVIII is approximately 175 kDa (based on its 1448 amino 
acid sequence) and has 86% pair-wise sequence homology with hFVIII. 
BAX 802 will be supplied as white lyophilized powder in 3 mL glass vials containing 
nominally 500 units per vial for reconstitution with 1.0 mL sterile water for injection. 
8.7.1 Packaging, Labeling, and Storage
BAX 802 will be supplied in a lyophilized form. For specific instructions for 
reconstitution, please refer to the Pharmacy Manual. A sufficient quantity of BAX 802
will be supplied to each study site, as well as an acknowledgement of receipt form.
The core label texts for all packaging units will be translated or adjusted, to be in 
compliance with applicable regulatory requirements, national laws in force and in 
accordance with the local languages. Minimally each vial will bear a label with the 
following information:

Sponsor name

Study number
For non-commercial use only

BAX 802
Page 39 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

Pharmaceutical dosage form

Route of administration

Name of IP and actual quantity of dose units

Batch number

Space on which to record the subject number

The statement ‘For clinical trial use only’ or ‘Caution: new drug limited by Federal 
Law to investigational use’ or ‘To be used only by a qualified Investigator’, as 
appropriate

Name, address and telephone number of the Sponsor, Contract Research 
Organization or Investigator, if appropriate

Storage conditions

Expiry or manufacturing date, as appropriate
The Investigator or designee will only dispense BAX 802 to subjects included in this 
study.
BAX 802 should be kept refrigerated at 2°C to 8°C (36°F to 46°F). The following 
precautions should be taken:

Do not freeze

Do not use if frozen, even if it has been thawed

Do not use beyond the expiration date printed on the carton or vial

Do not use after > 3 hours of reconstitution.
8.7.2 Reconstitution and Administration
The reconstitution procedures for BAX 802 are detailed in the Pharmacy Manual. 
Reconstituted BAX 802 should be kept and administered at room temperature and must 
be administered within 3 hours of reconstitution.
BAX 802 will be administered as an intravenous bolus infusion to the cubital vein per the 
dosing schema for major and minor surgeries (Table 5).
For non-commercial use only

BAX 802
Page 40 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3 Description of Treatment
8.7.3.1 FVIII Maintenance Plan
Based on the category (minor or major) and type of surgery and prior to intervention, the 
Investigator should outline the expected FVIII maintenance plan with target peak and 
trough levels covering the surgical, dental or invasive procedure until expected wound 
healing. The FVIII maintenance plan should be communicated to the medical 
director/designee to ensure that the recommendations regarding FVIII target levels as 
provided in the protocol are followed (see Table 5). Each FVIII maintenance plan for 
major surgeries requires prior approval of the medical director. The FVIII levels 
measured intra/postoperatively will be compared with the FVIII maintenance plan. Slight 
deviations from the predefined plan are allowed based on Investigators clinical judgment 
and/or available laboratory FVIII data.
It is recommended that the turnaround time for FVIII activity results from the local 
laboratories are ≤2 hours so that dosing decisions could be made and subjects are dosed 
adequately.
8.7.3.2 Perioperative Dosing
Adjustments to the dose and frequency of BAX 802 dosing during the intra- and 
postoperative period should follow the maintenance plan provided by the Investigator
prior to surgery. Adjustments must be based on regular FVIII activity measurements 
determined at pre- and post-dosing of BAX 802 and will depend on the type of the 
surgery performed and the intensity of the hemostatic challenge.
8.7.3.3 Dosing Schedule and Requirements
8.7.3.3.1 General
As described in Section 8.2.2, the loading dose will be calculated according to the 
following formula:
Loading dose of BAX 802 (administered approximately 1 to 2 hours prior to the 
surgery):

Major Surgery:
[80 × body weight (kg)] + [body weight (kg) × 40(1-[HCT%/100]) x anti-pFVIII 
inhibitor titer (BU)]

Minor Surgery:
[50 × body weight (kg)] + body weight (kg) × 40(1-[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU)]
For non-commercial use only

BAX 802
Page 41 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For example, for a 70 kg subject undergoing major surgery and having HCT 45% and 
anti-pFVIII inhibitor titer 3 BU, the loading dose of BAX 802 will be calculated as 
follows: 
80 (70) + 70 × 40(1-[45/100]) × 3 = 10,220 U
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels, and will require empirically based adjustments until 
hemostasis is achieved based on the following calculation below (Table 5):

Required (subsequent) dose (U) = [body weight (kg) × desired FVIII rise 
(U/dL or % of normal)]/1.2 (U/kg per U/dL).
Table 5: Dosing for Perioperative Management
Type of 
Surgery
Recommended FVIII Level
(% of normal or U/dL)
loading dose
Subsequent Dose
Major
(see 
Section 8.2.1.1)
Prior to surgery: ≥80%
Postoperative up to 72 hours 
(if not yet discharged): ≥80%
Postoperative Day 4 – Day 7
(if not yet discharged): ≥50% 
(if not yet discharged)
Postoperative Day 8 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels do not fall 
below 30% (left to the 
discretion of the Investigator
depending on the postoperative 
course)
[80 × body weight (kg)] + 
[body weight (kg) ×
40(1-[HCT%/100]) × anti-
pFVIII inhibitor titer (BU)a], 
administered approximately 1 
to 2 hours prior to the surgery
Titrate subsequent 
doses to maintain 
recommended FVIII 
trough levels and 
individual clinical 
response using 
following formula:
Required dose (U) 
= [body weight (kg) 
× desired FVIII rise 
(U/dL or % of 
normal)]/1.2 (U/kg 
per U/dL)
Minor 
(see 
Section 8.2.1.2)
Prior to surgery: ≥50%
Postoperative up to 72 hours 
(if not yet discharged): ≥50%
Postoperative Day 4 to 
discharge (if not yet 
discharged): it is recommended 
that the FVIII levels do not fall 
below 30% (left to the 
discretion of the Investigator
depending on the postoperative 
course)
[50 × body weight (kg)] + 
[body weight (kg) × 40(1-
[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU)a], 
administered approximately 1 
to 2 hours prior to the surgery
a Anti-pFVIII inhibitor titer and hematocrit information available from screening laboratory result will be 
used.
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
For non-commercial use only

BAX 802
Page 42 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If at any time during the study, a subject does not respond to BAX 802 therapy as 
anticipated either by the operating surgeon or hemophilia physician providing 
postoperative care, blood samples will be drawn for the determination of FVIII activity 
levels. In the event of unexplained, excessive bleeding, the subject will be treated by 
whatever means necessary until adequate hemostasis is achieved. If other rescue 
medications become necessary, the subject will subsequently be withdrawn from this 
BAX 802 surgery study and considered a treatment failure and assigned a GHEA score 
of 0 for remaining assessments (if any). Adverse events and the details of concomitant 
medication and blood product use coincident with the treatment of all unanticipated 
bleeding will be recorded. The use of adjunct antifibrinolytic therapy (such as tranexamic 
acid) is allowed if clinically indicated by the Investigator and/or according to the standard 
of care (SOC) of the subject’s institution.
8.7.3.3.2 Preoperative and loading dose
The subject will receive a loading dose calculated according to the formula described in 
Section 8.7.3.3.1 in order to maintain a minimum target FVIII level as required by the 
category and type of surgery. The recommended loading dose will be calculated by the 
Investigator.
The initial loading dose will be administered within 60 to 120 minutes prior to surgery 
(prior to incision/intubation).
The recommended FVIII target level is ≥80% for major surgeries/procedures and ≥50% 
for minor surgeries/procedures.
It is recommended that the surgery starts after FVIII levels have achieved target 
levels. However, if FVIII activity post loading dose is close to the target level, a 
supplemental dose of BAX 802 should be administered without further delaying the 
surgery, based on Investigator’s judgement. Close to the target for major and minor 
surgeries will be defined as levels of ≥ 70% for major and ≥ 40% for minor surgeries, 
respectively. This is 10% from the target, which is considered a normal assay variation.
If FVIII activity post loading dose is not close to the target level, a supplement dose of 
BAX 802 should be administered and surgery delayed until FVIII levels have achieved 
target levels or are in close range.
Subjects will receive subsequent doses of BAX 802 in order to achieve the FVIII target 
levels (see Table 5). All subsequent dosing of BAX 802 should be preceded by 
measurement of residual FVIII levels and dose adjustments must be based on the most 
recent residual FVIII activity levels. 
For non-commercial use only

BAX 802
Page 43 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Note: It is recommended that the plasma levels of FVIII do not exceed 200%.
Note: Dose adjustments should not be based on activated partial thromboplastin time
(aPTT) values.
8.7.3.3.3 Postoperative Dosing
All surgeries/procedures are to have FVIII levels monitored per the diagram in Figure 1:
Figure 1: Postoperative FVIII Monitoring
More frequent monitoring of FVIII activity is advised in subjects who have baseline anti-pFVIII inhibitor 
titers of ≥ 0.6 BU.
All subsequent dosing of BAX 802 must be preceded by measurement of residual FVIII levels pre-dose 
and FVIII level measurement 30 ±5 minutes post-dosing.
After the initial loading dose, optional re-dosings sufficient to raise FVIII levels to the 
appropriate level as defined for the type of surgery may be administered after a blood 
sample for FVIII determination has been drawn and the required FVIII levels by the local 
laboratory have been determined. 
FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as 
necessary.
FVIII activity level should also be determined within 4 to 6 hours 
following major or minor surgery, with dose adjustments as 
necessary.
FVIII activity level should be determined at least every 12 hours 
until 48 hours postoperative period (if not discharged yet), with 
dose adjustments as necessary.
Major Surgeries: Beginning on 
postoperative Day 3 (through 
discharge), subjects will have FVIII 
level measurement at least once per 
day in order to assess the adequacy 
of BAX 802 therapy during the 
postoperative period. For 
consistency, it is recommended that 
the daily blood draws are performed 
at the same time of the day, such as 
morning blood draws.
Minor Surgeries: In case the subject 
is hospitalized for more than 24 
hours, daily pre- and post-infusion 
FVIII level determinations as 
described for major surgery have to 
be performed and the dose adjusted 
according to the residual FVIII levels.
For non-commercial use only

BAX 802
Page 44 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
It is recommended that the FVIII trough levels are within the range targeted for major 
surgery during the treatment period as per Table 5. Dosing adjustments based on aPTT 
values are not allowed.
Any modifications of the FVIII maintenance plan that are deemed necessary during the 
postoperative period will be at the discretion of the Investigator and will be documented 
on the CRFs. 
At a minimum, a blood sample for FVIII determination must be drawn prior to any 
supplemental unscheduled FVIII infusion and 30 ±5 minutes post-dosing.
8.7.3.3.4 Dosing for Unrelated/Surgical Site Bleeding Episodes during the 
Postoperative Period
Unrelated bleeding episodes and surgical site bleeding episodes are defined in 
Section 11.2.3. 
The BAX 802 dosing regimen for treatment of these bleeding episodes will be based on 
the guidelines in Table 6. These guidelines may be adjusted by the Investigator based 
upon his or her clinical judgment.
Table 6: BAX 802 Treatment Guidelines for Unrelated/Surgical Site Bleeding 
Episodes
Type of Bleeding Episode
Recommended 
FVIII Level (%) BAX 802 Dose
Minor
Early hemarthrosis, mild muscle bleeding, or mild 
oral bleeding, including, epistaxis
20% to 40%
Required dose (U) = [body 
weight (kg) × desired FVIII 
risea (U/dL or % of normal)]/
1.2 (U/kg per U/dL)
Titrate subsequent doses to 
maintain recommended FVIII 
trough levels and individual 
clinical response until the 
bleeding resolves.
Moderate
Moderate bleeding into muscles, bleeding into the 
oral cavity, definite hemarthrosis, and known 
trauma
30% to 60%
Major
Significant gastrointestinal bleeding, intracranial, 
intra-abdominal, or intrathoracic bleeding, central 
nervous system bleeding, bleeding in the 
retropharyngeal or retroperitoneal spaces or 
iliopsoas sheath, fractures, head trauma
60% to 100%
a If the most recent residual FVIII activity level is from the measurement performed ≤4 hours of the 
bleeding episode, use this value to calculate desired FVIII rise. If the most recent residual FVIII activity 
level is from the measurement performed > 4 hours of the bleeding episode, the desired FVIII rise 
should be equivalent to the recommended FVIII level for that type of bleeding episode (as described in 
the column to the left).
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
For non-commercial use only

BAX 802
Page 45 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
It is critical that treatment of a bleed is initiated as soon as possible after occurrence 
of the bleeding episode.
Repeat infusions of BAX 802 can be administered to treat these bleeding episodes, as per 
Investigator’s discretion.
When bleeding is controlled, additional infusions of BAX 802 to maintain hemostasis are 
permitted, if required. Infusions given to treat and control the unrelated bleeding episode 
should be documented in the CRF.
If a subject is discharged or cannot be continued on IP at the study site, (e.g., because the 
clinic is closed on weekends), study participation should end at the time of hospital 
discharge and follow-up treatment, if any, should proceed with SOC products as per 
Investigator’s discretion.
Note: IP (BAX 802) will not be dispensed to the subjects for in-home use.
For a detailed description of bleeding episodes into different sites see Supplement 20.6.
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics
Commercially available gelatin sponges, topical thrombin, fibrin sealants, absorbable 
collagen preparations or anti-fibrinolytics (e.g., tranexamic acid, ɛ-amino caproic acid) 
may be used according to each institution’s SOC. Details, including the dose, of all 
adjunctive hemostatic medication used will be recorded in the CRFs designed for this 
study and the reason for use given. 
Thrombosis prophylaxis can be administered at the discretion of the Investigator
according to the SOC of each institution and recorded into the respective CRF. 
Thrombosis prophylaxis should preferably consist of mechanical measures such as 
intermittent pneumatic compression (IPC), compression stockings and early mobilization. 
Pharmacologic thrombosis prophylaxis such as low molecular weight heparin (LMWH) 
may be considered for certain surgical interventions such as major orthopedic surgery 
after careful evaluation by the Investigator of the potential risks and benefits.
For non-commercial use only

BAX 802
Page 46 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.5 Investigational Product Accountability
The Investigator will ensure that the IP(s) is stored as specified in the protocol and that 
the storage area is secured, with access limited to authorized study personnel. The 
Investigator will maintain records that the IP(s) was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received and 
disposition. The IP(s) must be dispensed only at the study site or other suitable location 
(e.g., infusion center, as applicable per study design). Records will be maintained that 
includes the subject identification code (SIC), dispensation date, and amount dispensed. 
All remaining partially used and/or unused IP(s) will be returned to the sponsor or 
sponsor’s representative after study completion/termination, or destroyed with the 
permission of the sponsor in accordance with applicable laws and study site procedures.
If IP(s) is to be destroyed, the Investigator will provide documentation in accordance with 
sponsor’s specifications.
8.8 Source Data
Per ICH GCP, source data are defined as all information in original records and certified 
copies of original records of clinical findings, observations, or other activities in a clinical 
trial that are necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents (original records or certified copies), which may be in 
paper and/or electronic format. Source data for this study comprise the following: 
hospital records, medical records, clinical and office charts, laboratory notes, memoranda, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical study.
No data will be entered directly onto the case report form (CRF).
For additional information on study documentation and CRFs, see Section 17.2.
For non-commercial use only

BAX 802
Page 47 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subject requires a major or minor elective surgical, dental or other invasive 
procedure
2.
Subject is male and ≥ 12 to ≤ 75 years old at the time of screening
3.
Subject has provided signed informed consent (and assent for adolescent subjects, 
as applicable) in accordance with local regulatory requirements
4.
Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤2%) 
CHA with inhibitors to hFVIII of ≥ 0.6 BU, as tested at screening at the central 
laboratory
5.
Subject is not currently receiving or has recently received (< 30 days) ITI therapy
6.
Subject has a Karnofsky performance score of ≥60 at screening
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable 
disease and CD4+ count ≥200 cells/mm3 at screening
8.
Subject is hepatitis C virus negative (HCV-) by antibody or polymerase chain 
reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease. (If positive, 
the antibody titer will be confirmed by PCR.)
9.
Subject is willing and able to comply with the requirements of the protocol.
9.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
The subject 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-pFVIII inhibitor > 10 BU prior to surgery
5.
Platelet count < 100,000/µL at screening
6.
Subject has another active coagulation disorder, other than hemophilia A, as per the 
medical history
For non-commercial use only

BAX 802
Page 48 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7.
Planned use of α-interferon with or without ribavarin 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 rpFVIII, or hamster or murine proteins
9.
Subject has an ongoing or recent (within 3 months of screening) thrombo-embolic 
disease, fibrinolysis or disseminated intravascular coagulation (DIC)
10. Subject has been exposed to an IP within 30 days prior to enrollment or is 
scheduled to participate in another clinical study involving an IP or investigational 
device during the course of this study
11. Subject is unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the Investigator. 
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw (i.e., reduce the degree of participation in the 
study) consent for continued participation and data collection. The reason for withdrawal 
will be recorded on the End of Study CRF. Assessments to be performed at the
termination visit (including in cases of withdraw or discontinuation) are described in 
Section 10.7, Section 20.3, and Section 20.4.
Discontinuation (ie, complete withdrawal from study participation) may be due to 
dropout (i.e., active discontinuation by subject) or loss to follow-up (i.e., discontinuation 
by subject without notice or action). Additionally, the Investigator and sponsor have the 
discretion to discontinue any subject from the study if, in their judgment, continued 
participation would pose an unacceptable risk for the subject.
Subjects also will be withdrawn from treatment or discontinued from further study 
participation for the following reasons:

AEs/SAEs that in the Investigator’s or sponsor’s opinion, poses an unacceptable 
risk for continued dosing in the subject

Participation in another clinical study involving an IP during the course of the study

The subject experiences a severe anaphylactic reaction

The subject had uncontrolled hemorrhage that was the result of inadequate 
therapeutic response despite proper dosing of BAX 802, necessitating rescue 
therapy with bypassing agents.
For non-commercial use only

BAX 802
Page 49 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10. STUDY PROCEDURES
10.1 Informed Consent
Any patient who provides informed consent or assent, as applicable (i.e., signs and dates 
the informed consent form (ICF) and assent form, if applicable) is considered a subject in 
the study.
10.2 Subject Identification Code
The following series of numbers will comprise the SIC: protocol identifier (241502) to be 
provided by the sponsor, 3-digit number study site number (e.g., 002) to be provided by 
the sponsor, and 3-digit subject number (e.g., 003) reflecting the order of providing
informed consent. For example, the third subject who signed an ICF at study site 002 will 
be identified as Subject 241502-002003. All study documents (e.g., CRFs, clinical 
documentation, sample containers, drug accountability logs, etc.) will be identified with 
the SIC. Additionally, a uniquely coded SIC(s) is permitted as long as it does not contain 
a combination of information that allows identification of a subject (e.g., collection of a 
subject’s initials and birth date would not be permitted), in compliance with laws 
governing data privacy.
10.3 Screening and Study Visits
The study site is responsible for maintaining a screening log that includes all subjects 
who provided informed consent. The log also will serve to document the reason for 
screening failure.
All screening data will be collected and reported in CRFs, regardless of screening 
outcome. If a subject is re-screened, the End of Study CRF should be completed, and a 
new ICF, new SIC and new CRF are required for that subject. 
Subjects who fail screening due to a single laboratory test result that does not meet 
eligibility criteria may have that laboratory test repeated at the discretion of the 
Investigator. This will include a repeat of only the failed assessment; complete re-
screening will not be necessary. In these cases, a new SIC is not required; the subject will 
maintain their original SIC. The repeat of a screening assessment is allowed once. A 
repeat assessment must take place within 42 days of the initial screening for any subject 
requiring repeat of a screening assessment. If this timeframe is exceeded, then all 
screening assessments must be repeated and the subject assigned a new SIC. Exemptions 
are possible for administrative reasons and have to be approved by the sponsor. Subjects 
with an inadequate interval between screening and prior IP drug (other than BAX 802) 
administration or prior participation in a drug or device study (i.e., 30 days), may be 
re-screened only once and only when the required interval is reached. 
For non-commercial use only

BAX 802
Page 50 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The screening assessment should be performed within 45 days prior to the planned 
elective surgery.
The overall study design is illustrated in Supplement Figure 2. Details on the procedures 
to be performed at each study visit, including screening, can be found in Supplement 20.3
and Supplement 20.4.
10.4 Study Periods
The study will be divided into 5 periods: 
1.
Screening
2.
Preoperative 
3.
Intraoperative
4.
Postoperative
5.
End of study 
A detailed description of study procedures per study period is provided in 
Supplement 20.1.
10.4.1 Discharge/End of Study Visit
Discharge Visit will be performed when the subject is discharged. The End of Study Visit 
will be performed 42 ± 7 days following the completion of the surgical procedure. In 
cases where the Discharge Visit would occur within 3 days of the End of Study Visit, the 
respective visits can be done as a single visit. Sites must make every effort to complete 
3 independent GHEA assessments (GHEA1, GHEA2, GHEA3) for both minor and major 
procedures, preferably allowing for as much time as possible to pass between assessments 
within the windows specified in this protocol.
10.4.2 Antibody Testing Visit
A visit will be performed between 7 to 14 days after last perioperative dose of BAX 802. 
Study procedures will be performed as per Table 9 and blood samples will be collected 
for antibody testing and other tests as per Table 10.
10.4.3 Unscheduled Visit
An unscheduled visit could be performed for events such as antibody testing or 
management of bleeding episodes.
For non-commercial use only

BAX 802
Page 51 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.5 Medications and Non-Drug Therapies 
The following medications are not permitted before discharge (unless used as rescue 
medications or used to treat unrelated/surgical site bleeding episodes as specified below):
Medications:

Hemophilia inhibitor bypassing therapy (recombinant factor VIIa [NovoSeven] 
within 3 hours or activated prothrombin complex concentrate [aPCC; FEIBA]) 
within 12 hours prior to initial BAX 802 administration) unless used as a rescue 
medication (Section 10.5) after failure/study withdrawal or used to treat 
unrelated/surgical site bleeding episodes (Section 11.2.3).

Hemophilia medication other than BAX 802 at any time during the study. 
A subject who has taken any of these medications will be considered a protocol deviation.
The following medications and non-drug therapies are permitted within 30 days before 
study entry and during the course of the study:
Medications:

The management of a serious thrombo-embolic event may require anticoagulant 
medication and this may need to be administered concurrent with the use of 
BAX 802 to ensure that a re-bleed or continuing severe hemorrhage does not occur 
on withdrawal of BAX 802 (see Section 10.6). In such instances the Sponsor’s 
medical monitor should be consulted.

Any medications deemed necessary by the subject’s physician to treat or prevent 
any medical condition (with the exception of those listed as not permitted)

Any over-the-counter medication used by the subject to treat symptoms or signs of 
any medical condition

Supplemental vitamins and minerals
Non-drug therapies:

Any non-drug therapy (e.g., physiotherapy) deemed necessary by the subject’s 
physician to treat or prevent any medical condition
For non-commercial use only

BAX 802
Page 52 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.6 Rescue Medications
Bypassing agents (FEIBA or NovoSeven) can be used as a rescue medication if expected 
plasma FVIII activity levels are not attained or if bleeding is not controlled despite proper 
dosing of BAX 802 during the intra- or postoperative period of the study. 
Note: At least 2 doses of BAX 802 need to be administered before the subject is 
considered to be a treatment failure and switched to the rescue medication.
10.7 Subject Completion/Discontinuation
A subject is considered to have completed the study when he ceases active participation 
in the study because the subject has, or is presumed to have, completed all study
procedures according with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation CRF, including: completed, screen failure, AE (e.g., death), 
discontinuation by subject (e.g., lost to follow-up [defined as 3 documented unsuccessful 
attempts to contact the subject], and dropout), physician decision (e.g., progressive 
disease, non-compliance with IP/protocol violation(s), recovery), study terminated by 
sponsor, or other (reason to be specified by the Investigator, e.g., technical problems). 
Regardless of the reason, all data available for the subject up to the time of 
completion/discontinuation should be recorded on the appropriate CRF.
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit. If the completion/termination visit is done as an additional, 
unscheduled visit, the assessment results shall be recorded with the 
completion/termination visit. If a subject terminates participation in the study and does 
not return for the completion/termination visit, their last recorded assessments shall 
remain recorded with their last visit. The reason for discontinuation will be recorded, and 
the data collected up to the time of discontinuation will be used in the analysis and 
included in the clinical study report. If additional assessments are required, the 
assessments shall be recorded separately. Assessments to be performed at the termination 
visit (including in cases of withdraw or discontinuation) can be found in Supplement 20.3
and Supplement 20.4.
In the event of subject discontinuation due to an AE, clinical and/or laboratory 
investigations that are beyond the scope of the required study observations/assessments 
may be performed as part of the evaluation of the event. These investigations will take 
place under the direction of the Investigator in consultation with the sponsor, and the 
details of the outcome may be reported to the appropriate regulatory authorities by the 
sponsor.
For non-commercial use only

BAX 802
Page 53 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.8 Procedures for Monitoring Subject Compliance
Subject compliance with the procedures and treatment(s) outlined above will be 
monitored by direct review of the subject’s source data at the sites and evaluated against 
the protocol requirements. Additionally, electronic edit checks will be performed on all 
protocol-specified procedures and treatment data that are collected to ensure quality and 
accuracy. Deviations from the protocol-specified procedures and treatments will be noted 
in the final study report.
All study procedures are to be performed under the direct supervision of the 
Investigator/a licensed healthcare professional at the study site, and thus, no separate 
procedures will be used to monitor subject compliance.
For non-commercial use only

BAX 802
Page 54 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11. ASSESSMENT OF EFFICACY
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score
The primary outcome measure is the proportion of all surgical or other invasive 
procedures with a “good” or “excellent” response measured by GHEA. The GHEA score
is composed of 3 individual categorical ratings (GHEA1, GHEA2, GHEA3) which will 
be added together to form the total GHEA score according to Table 1 (see Section 8.4.1).
11.2 Secondary Efficacy Endpoints
11.2.1 Blood Loss
The observed versus predicted (recorded prior to surgery) operative blood loss will be 
described for the period from initiation of the intervention to discharge or 24 to 72 hours
after the last perioperative treatment dose of BAX 802 (whichever is first), as applicable.
Prior to the surgery, the surgeon/Investigator will predict the estimated volume (in mL) of 
the expected average and maximum blood loss for the planned surgical intervention in a 
hemostatically normal individual of the same sex, age, and stature as the study subject, 
for intraoperative, postoperative, and overall perioperative time periods. Every effort 
should be made to predict the volume as precisely as possible, also taking into account, 
for example, the use of a tourniquet or placement of a postoperative drain and whether or 
not suction is used. The estimate will be for the intraoperative time period and from 
completion of the procedure until approximately 24 hours post-surgery and for the overall 
perioperative time period (assessed at discharge or 24 to 72 hours after the last 
perioperative treatment dose of BAX 802). The expected normal/average, and maximal 
blood loss and transfusion requirement estimate will be timestamped into the source 
documentation and/or blood loss form prior to the surgery, and then transferred into the 
CRF. No changes will be allowed to these estimates after the surgery.
The intraoperative blood loss will be measured by determining the volume of blood and 
fluid removal through suction into the collection container (waste box and/or cell saver) 
and the estimated blood loss into swabs and towels during the procedure, per the 
anesthesiologist’s record. 
Postoperatively, blood loss will be determined by the drainage volume collected, which 
will mainly consist of drainage fluid via vacuum or gravity drain, as applicable. In cases 
where no drain is present, blood loss will be determined by the surgeon’s clinical 
judgment, as applicable or entered as “not available”.
For non-commercial use only

BAX 802
Page 55 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.2 Blood Transfusions
The type and volume (in mL) of blood products will be recorded from initiation of the 
intervention to discharge or 24 to 72 hours after last perioperative treatment dose of 
BAX 802 (whichever is earlier). Furthermore, also salvage of blood obtained from 
autologous transfusion systems, (e.g., cell savers) will be recorded. In addition, the type 
and volume of fluid replacement and volume expanders will be recorded as concomitant 
medication (e.g., volume of salvaged blood, red blood cells, platelets and other blood 
products transfused).
11.2.3 Bleeding Episodes
 
 
 
, until the time of discharge or until the subject resumes his previous 
treatment regimen, whichever is later. 
Any subject who is deemed to have excessive, unexplained bleeding will have blood 
drawn for measurement of FVIII levels.
Bleeding episodes will be classified as follows:

Unrelated bleeding episodes: an unrelated bleeding episode is defined as any 
bleeding occurring at a different anatomical site than the surgery site during the 
postoperative period. 

Surgical site bleeding episodes: Surgical site bleeding episodes are any bleeding at 
the surgical/procedure site which occurs after discharge (related to the perioperative 
procedure) or 72 hours after the last perioperative treatment dose of BAX 802 (if 
hospitalization is prolonged for reasons other than perioperative procedures), 
whichever is earlier.
These bleeding episodes will be treated as follows:

If these unrelated bleeding episodes or surgical site bleeding episodes occur during 
the subject’s stay in hospital, it is recommended that subjects are treated with 
BAX 802. BAX 802 will be dosed as per the most recent residual FVIII activity 
level and clinical judgment using the dosing regimen provided in Table 6
[Required dose = body weight (kg) × desired FVIII rise (U/dL or % of normal)]/
1.2 (U/kg per U/dL)]. All subsequent dosing of BAX 802 should be preceded by 
measurement of residual FVIII levels and dose adjustments must be based on the 
most recent residual FVIII activity levels.
For non-commercial use only

BAX 802
Page 56 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

If these unrelated bleeding episodes or surgical site bleeding episodes occur after 
the subject has been discharged, subjects may be treated with BAX 802 or SOC, as 
per Investigator's discretion. Note: IP (BAX 802) will not be dispensed to the 
subjects for in-home use.
An unscheduled visit could be performed for the management of bleeding episodes.
11.2.4 BAX 802 Administration
The daily and total weight-adjusted administration of BAX 802 per subject will be 
recorded.
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical Site
Bleeding Episodes
An unrelated bleeding episode is defined as any bleeding occurring at a different 
anatomical site than the surgery site during the postoperative period. Surgical site 
bleeding episodes are any bleeding at the surgical/procedure site which occurs after 
discharge (related to the perioperative procedure) or 72 hours after the last perioperative 
treatment dose of BAX 802 (if hospitalization is prolonged for reasons other than 
perioperative procedures), whichever is earlier. These bleeding episodes will be treated as 
per Section 11.2.3.
If subject is treated with BAX 802 for unrelated bleeding episodes or surgical site 
bleeding episodes, the subject will rate the severity (minor, moderate, or major) of the 
bleeding episode and will rate the overall treatment response at 24 ±2 hours after the 
initiation of treatment and at the resolution of bleed (if not resolved within 24 hours) 
using a 4-point efficacy rating scale (Table 7). Since the efficacy rating is based to a large 
degree on cessation of pain, the Investigator/subject shall, particularly in the event of 
injury-related bleeding into ≥1 location, consider the injury-related symptoms when 
performing the efficacy rating 24 hours after initiating treatment and at resolution of 
bleed. Data should be collected as an unscheduled visit.
As per Table 5, multiple infusions of BAX 802 may be administered for the treatment of 
a bleeding episode. The overall response to all infusions combined is the rating that will 
be recorded at resolution of bleed.
For non-commercial use only

BAX 802
Page 57 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 7: Efficacy Rating Scale for Treatment of Unrelated/Surgical Site Bleeding 
Episodes
Excellent
Full relief of pain and/or cessation of objective signs of bleeding (e.g., swelling, 
tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) 
after a single infusion. No additional infusion is required for the control of bleeding. 
Administration of further infusions to maintain hemostasis would not affect this scoring.
Good
Definite pain relief and/or improvement in signs of bleeding after a single infusion. 
Possibly requires more than 1 infusion for complete resolution.
Fair
Probable and/or slight relief of pain and slight improvement in signs of bleeding after a 
single infusion. Required more than 1 infusion for complete resolution.
None
No improvement or condition worsens.
As per Table 5, multiple infusions of BAX 802 may be administered for the treatment of 
a bleeding episode. The overall response to all infusions combined is the rating that will 
be recorded at resolution of bleed.
11.3 Factor VIII Activity
Blood will be obtained for assessment of FVIII activity at screening (tests to be 
performed at the central laboratory). Results from local laboratory will be used to 
make any dosing decisions.
Blood will be obtained for assessment of FVIII activity for patient management purposes 
at the following time points (tests to be performed at the local laboratory, with 
additional back-up samples to be tested in 1 batch at the central laboratory):

Within 30 minutes prior to the administration of the initial loading dose 
preoperatively and 30 ±5 minutes post-infusion. If re-dosing with BAX 802 is 
required to obtain the required FVIII levels, an additional blood sample needs to 
be drawn 30 ±5 minutes following the re-dosing with BAX 802.

Postoperatively until day of discharge from the investigative site: daily within 
30 minutes prior to the infusion of BAX 802 and 30 ±5 minutes post-infusion. 
Pre- and post-dosing blood draws for FVIII activity level determination should 
also be performed for each BAX 802 administration.

FVIII activity will also be assessed if the subject has excessive, unexplained 
bleeding at any time intra-or postoperatively, or whenever deemed necessary 
according to the institution’s SOC.
For non-commercial use only

BAX 802
Page 58 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.3.1 Blood Sampling and Processing for FVIII Analysis
At each blood sampling time point whole blood will be collected in blood sampling tubes 
will be collected in S-Monovette® tubes (Sarstedt, Nümbrecht, Germany) containing 
3.2% trisodium citrate, or equivalent blood drawing equipment (e.g., Vacutainer tubes), 
and immediately mixed. The citrated whole blood samples will be capped and transported 
at room temperature (i.e., 20 to 25°C) to the local clinical laboratory for centrifugation, 
processing, and storage. Monovettes must be kept in an upright position at all times to 
avoid leakage.
All samples taken through 6 hours post-dosing will be collected from an extremity other 
than that used for the infusion of study product. Thereafter, either extremity may be used 
to obtain samples.
If the subject has a central venous catheter, the central line should be used to administer 
the infusion and a peripheral venipuncture should be used to collect the blood samples. 
In the event that a blood sample must be drawn through the central line used for 
administration of IP, the line must first be flushed with 5 mL normal saline or other 
suitable catheter flush solution that does not contain anticoagulant. At least 5 mL of 
whole blood must be collected and discarded prior to obtaining the sample. 
All citrated plasma samples will be stored and shipped to the central laboratory at 
≤-70°C for testing. 
All back-up samples collected during the perioperative period will be shipped to the 
central laboratory as soon as possible in 1 batch and analyzed, as needed. 
Blood samples will be analyzed for FVIII activity (1-stage clotting assay and the 
chromogenic assay) at the central laboratory. The 1-stage FVIII activity assay will serve 
as the primary assay; the chromogenic assay of FVIII activity will be used to provide
supportive data. Local laboratories are expected to use a 1-stage clotting assay.
For non-commercial use only

BAX 802
Page 59 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY
12.1 Adverse Events
12.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP 
that does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom (e.g., rash, pain, discomfort, fever, dizziness, etc.), disease (e.g., peritonitis, 
bacteremia, etc.), or outcome of death temporally associated with the use of an IP, 
whether or not considered causally related to the IP.
12.1.1.1 Serious Adverse Event
An SAE is defined as an untoward medical occurrence that at any dose meets 1 or more 
of the following criteria:

Outcome is fatal/results in death (including fetal death)

Is life-threatening – defined as an event in which the subject was, in the judgment 
of the Investigator, at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death had it been more severe.

Requires inpatient hospitalization or results in prolongation of an existing 
hospitalization – inpatient hospitalization refers to any inpatient admission, 
regardless of length of stay.

Results in persistent or significant disability/incapacity (i.e., a substantial disruption 
of a person’s ability to conduct normal life functions)

Is a congenital anomaly/birth defect

Is a medically important event – a medical event that may not be immediately
life-threatening or result in death or require hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the definitions above. Examples of such events are:

Intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependence or drug abuse.

Reviewed and confirmed seroconversion for HIV, hepatitis A virus (HAV), 
hepatitis B virus (HBV), HCV, hepatitis E virus (HEV), or parvovirus B19 
(B19V).
For non-commercial use only

BAX 802
Page 60 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

Thrombo-embolic events (e.g., stroke, myocardial infarction, deep vein 
thrombosis, pulmonary embolism).

The confirmed development of de-novo anti-pFVIII inhibitory antibodies or 
increases of > 10 BU in pre-existing titers of anti-pFVIII inhibitory antibodies 
(see Section 12.1.1.1.1)
Planned hospitalization for any study procedures as per the protocol will not be 
considered as an SAE.
12.1.1.1.1 Inhibitory Serious Adverse Events
The development of de-novo anti-pFVIII inhibitory antibodies (≥0.6 BU) must be 
confirmed with a second blood draw 7 to 14 days after the initial confirmed positive de 
novo result (or repeat testing of original sample if a second draw is not possible). 
Confirmation of de novo inhibitory antibodies or a confirmed increase of > 10 BU in 
pre-existing titers of anti-pFVIII inhibitory antibodies must be reported as a SAE within 
24 hours, and followed up.
Increases in pre-existing titers of anti-pFVIII inhibitory antibodies will require a second 
confirmatory test 7 to 14 days after the initial confirmed positive increase (or repeat 
testing of original sample if a second draw is not possible). If the protocol-defined 
significant increase (> 10 BU) is confirmed, it will be reported as an SAE.
Safety will be further monitored by the Investigator and medical monitor to evaluate the 
clinical significance of the inhibitor level. Although the development of, or increase in, 
anti-pFVIII inhibitory antibody titers may not necessarily indicate a failure of response to 
BAX 802, the inhibitor levels and patient response will be closely monitored and an 
alternative therapy will be considered for lack of efficacy, if applicable.
12.1.1.2 Suspected Unexpected Serious Adverse Reaction
Any suspected adverse reaction to study treatment that is both serious and unexpected. 
The event(s) must meet all of the following:

Suspected adverse reaction

Serious

Unexpected

Assessed as related to study treatment
For non-commercial use only

BAX 802
Page 61 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Once determined to meet the criteria for a SUSAR, an SAE should be submitted to 
regulatory agencies expeditiously.
12.1.1.3 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.4 Unexpected Adverse Events
An unexpected AE is an AE whose nature, severity, specificity, or outcome is not 
consistent with the term, representation, or description used in the Reference Safety 
Information (RSI). “Unexpected” also refers to the AEs that are mentioned in the IB as 
occurring with a class of drugs or as anticipated from the pharmacological properties of 
the product, but are not specifically mentioned as occurring with the particular product 
under investigation. The expectedness of AEs will be determined by the sponsor using 
the Company Core Data Sheet for OBIZUR as the RSI. This determination will include 
considerations such as the number of AEs previously observed, but not on the basis of 
what might be anticipated from the pharmacological properties of a product.
12.1.1.5 Preexisting Diseases
Preexisting diseases that are present before entry in to the study are described in the 
medical history, and those that manifest with the same severity, frequency, or duration 
after IP exposure, will not be recorded as AEs. However, when there is an increase in the 
severity, duration, or frequency of a preexisting disease, the event must be described on 
the AE CRF.
12.1.2 Assessment of Adverse Events
For the purposes of this study, the following non-serious events experienced after the first 
IP exposure are collected under other study endpoints and thus are not reportable on the 
AE CRF, nor will they be included in the analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they will 
be assessed as part of the efficacy assessments. However, the Investigator may decide 
that the event is an AE if the event also would have occurred in a normal patient under 
the same circumstances. If a bleeding episode was caused by an injury, the injury will be 
reported as an AE. All bleeding episodes must be entered in the bleeding event CRF.
For non-commercial use only

BAX 802
Page 62 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
All other/Each AE from the first IP exposure until study completion or discontinuation 
date will be described on the AE CRF using the medical diagnosis (preferred), or, if no 
diagnosis could be established at the time of reporting the AE, a symptom or sign, in 
standard medical terminology in order to avoid the use of vague, ambiguous, or 
colloquial expressions (see definition in Section 12.1). Each AE will be evaluated by the 
Investigator for:

Seriousness as defined in Section 12.1.1.1

Severity as defined in Section 12.1.2.1

Causal relationship to IP exposure or study procedure as defined in Section 12.1.2.2
For each AE, the outcome (i.e., recovering/resolving, recovered/resolved, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, or unknown) and if 
applicable action taken (i.e., dose increased, dose not changed, dose reduced, drug 
interrupted, drug withdrawn, not applicable, or unknown) will also be recorded on the AE 
CRF. Recovering/resolving AEs will be followed until resolution, medically stabilized, or
30 days after the study completion/termination visit, whichever comes first. If the 
severity rating for an ongoing AE changes before the event resolves, the original AE 
report will be revised (i.e., the event will not be reported as separate AE). During the 
course of any AE, the highest severity rating will be reported.
Deviations from the protocol-specified dosage (including overdosing, underdosing, 
abuse, and withdrawal), treatment errors (including incorrect route of administration, use 
of an incorrect product, and deviations from the protocol-defined dosing schedule), 
failures of expected pharmacological actions, and unexpected therapeutic or clinical 
benefits will be followed with regard to occurrence of AEs, lack of efficacy, and/or other 
observations because these events may be reportable to regulatory authorities.
If an Investigator becomes aware of an SAE occurring in a subject after study 
completion, the SAE must be reported on the provided SAE Report Form within 24 hours 
after awareness; no additional reporting on CRFs is necessary.
For non-commercial use only

BAX 802
Page 63 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.1.2.1 Severity
The Investigator will assess the severity of each AE using his/her clinical expertise and 
judgment based on the most appropriate description below:

Mild

The AE is a transient discomfort and does not interfere in a significant manner 
with the subject’s normal functioning level.

The AE resolves spontaneously or may require minimal therapeutic 
intervention.

Moderate

The AE produces limited impairment of function and may require therapeutic 
intervention.

The AE produces no sequela/sequelae.

Severe

The AE results in a marked impairment of function and may lead to temporary 
inability to resume usual life pattern.

The AE produces sequela/sequelae, which require (prolonged) therapeutic 
intervention.
These severity definitions will also be used to assess the severity of an AE with a 
study-related procedure(s), if necessary.
12.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, for 
example, assessment of temporal relationships, dechallenge/rechallenge information, 
association (or lack of association) with underlying disease, presence (or absence) of a 
more likely cause, and physiological plausibility. For each AE, the Investigator will 
assess the causal relationship between the IP and the AE using his/her clinical expertise 
and judgment according to the following most appropriate algorithm for the 
circumstances of the AE:
Not related (both circumstances must be met)
Is due to underlying or concurrent illness, complications, concurrent 
treatments, or effects of concurrent drugs
For non-commercial use only

BAX 802
Page 64 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Is not associated with the IP (i.e., does not follow a reasonable temporal 
relationship to the administration of IP or has a much more likely alternative 
etiology).
Unlikely related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists
Possibly related (both circumstances must be met)
Follows a reasonable temporal relationship to the administration of IP
An alternative etiology is equally or less likely compared to the potential 
relationship to the IP
Probably related (both circumstances must be met)
Follows a strong temporal relationship to the administration of IP, which may 
include but is not limited to the following:
o
Reappearance of a similar reaction upon re-administration (positive 
rechallenge)
o
Positive results in a drug sensitivity test (skin test, etc.)
o
Toxic level of the IP as evidenced by measurement of the IP 
concentrations in the blood or other bodily fluid
Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related, the Investigator shall provide the 
alternative etiology. These causality definitions will also be used to assess the 
relationship of an AE with a study-related procedure(s), if necessary.
12.1.2.3 Safety Reporting
Adverse events/SAEs will be assessed at all study visits as outlined in the Schedule of 
Study Procedures and Assessments (see Table 9) and Section 12.1.
Adverse Events/SAEs are to be recorded on the AE page of the CRF. Each event should 
be recorded separately.
Any SAE, including death due to any cause, which occurs during this study, 
whether or not related to the IP, must be reported immediately (within 24 hours 
of the study center’s first knowledge of the event). 
For non-commercial use only

BAX 802
Page 65 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Any SAEs must be reported using the paper SAE Report Form to meet the 24 hour 
timeline requirement (for contacts and instructions refer to the SAE Report Form).
The initial SAE information reported on the applicable SAE Report Form must at least 
include the following:

Protocol number

Subject identification number and demographics (gender, age at onset of event 
and/or date of birth)

IP exposure

Medical Term for Event (Diagnosis preferably)

Description of the (S)AE, including:

Date of onset

(S)AE treatment (drug, dose, route of administration)

Causal relationship by the Investigator

Measures taken (i.e., action taken regarding IP in direct relationship to the AE)

Seriousness criteria (i.e., death, life-threatening, or other criterion)

Cause of death

Autopsy findings (if available)

Name, address, fax number, email, and telephone number of the reporting

Investigator
12.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the 
protocol, in order to protect subjects participating in a clinical trial from immediate harm. 
Urgent safety measures may be taken by the sponsor or clinical Investigator, and may 
include any of the following:
Immediate change in study design or study procedures
Temporary or permanent halt of a given clinical trial or trials
Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety
For non-commercial use only

BAX 802
Page 66 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The Investigator may take appropriate urgent safety measures in order to protect subjects 
against any immediate hazard to their health or safety. The measures should be taken 
immediately and may be taken without prior authorization from the sponsor. In the 
event(s) of an apparent immediate hazard to the subject, the Investigator will notify the
sponsor immediately by phone and confirm notification to the sponsor in writing as soon 
as possible, but within 1 calendar day after the change is implemented. The sponsor will 
also ensure the responsible ethics committee (ECs) and relevant competent authority(s) 
are notified of the urgent safety measures in such cases according to local regulations.
12.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to IP are not 
considered AEs (according to the definition of AE, see Section 12.1). However, each 
serious untoward medical occurrence experienced before the first IP exposure (i.e., from 
the time of signed informed consent up to but not including the first IP exposure) will be 
described on the AE CRF (and SAE Report Form if CRF is not available). These events 
will not be considered as SAEs and will not be included in the analysis of SAEs.
For the purposes of this study, each of the following non-serious events experienced after 
the first exposure to IP will not be considered an AE, and thus, not included in the 
analysis of AEs:

Bleeding episodes are part of the underlying disease and therefore are not AEs; they 
will be assessed as part of the efficacy assessments. If a bleeding episode was 
caused by an injury, the injury would not be reported as an AE, unless it resulted in 
a medical finding other than a bleeding episode (e.g., abrasion of skin). Therefore, 
any hemophilia-related event (e.g., hemarthrosis [presenting as swelling, pain, and 
decreased range of motion], bruising, hemorrhages, or pain at bleeding episode site) 
will not be reported as AEs. However, the Investigator may decide that the event is 
an AE if the event also would have occurred in a normal patient under the same 
circumstances.
12.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to 
identity, quality, durability, reliability, safety and performance of the product but did not 
result in an AE. The NMCs include but are not limited to the following:

A failure of a product to exhibit its expected pharmacological activity and/or design 
function, e.g., reconstitution difficulty

Missing components
For non-commercial use only

BAX 802
Page 67 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

Damage to the product or unit carton

A mislabeled product (e.g., potential counterfeiting/tampering)

A bacteriological, chemical, or physical change or deterioration of the product 
causing it to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the 
sponsor within 1 business day. If requested, defective product(s) will be returned to the 
sponsor for inspection and analysis according to procedures.
12.5 Medical, Medication, and Non-Drug Therapy History
At screening, the subject’s medical history will be described for the following body 
systems including severity (defined in Section 12.1.2.1) or surgery and start and end 
dates, if known: eyes, ears, nose, and throat; respiratory; cardiovascular; gastrointestinal; 
musculoskeletal; neurological; endocrine; hematopoietic/lymphatic; dermatological; and 
genitourinary.
Medical history will include the collection of hemophilia history, bleeding episode 
history, and history of aPCC or rFVIIA usage for 6 months prior to screening. Relevant 
medical and surgical history and all medications taken 3 months prior to screening will 
also be collected.
All medications taken and non-drug therapies received within 3 months before providing 
informed consent until completion/termination will be recorded on the concomitant 
medications and non-drug therapies CRFs.
12.6 Physical Examinations
At screening and subsequent study visits (as described in Table 9), a physical 
examination will be performed on the following body systems: general appearance, head 
and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and 
joints, lymph nodes, skin, and neurological. At screening, if an abnormal condition is 
detected, the condition will be described on the medical history CRF. At study visits, if a 
new abnormal or worsened abnormal pre-existing condition is detected, the condition will 
be described on the AE CRF. If the abnormal value was not deemed an AE because it 
was due to an error, due to a preexisting disease (described in Section 12.1.1.5), not 
clinically significant, a symptom of a new/worsened condition already recorded as an AE, 
or due to another issue that will be specified, the Investigator will record the justification 
on the source record.
For non-commercial use only

BAX 802
Page 68 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7 Clinical Laboratory Parameters
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, 
creatinine, and glucose.
The hematology panel will consist of complete blood count (hemoglobin, HCT, 
erythrocytes [i.e., red blood cell count), and leukocytes (i.e., white blood cell count]) with 
differential (i.e., basophils, eosinophils, lymphocytes, monocytes, and neutrophils) and 
platelet counts.
Clinical chemistry and hematology assessments will be performed on EDTA-
anticoagulated serum and whole blood, respectively, at the central laboratory. The 
frequency of blood draws for clinical and hematology assessments is provided in 
Table 10. 
Details of blood sampling volumes are presented in the laboratory manual and master 
ICF.
12.7.1 Hematology, Clinical Chemistry, and Urinalysis
The hematology panel will consist of complete blood count (hemoglobin, HCT, 
erythrocytes [i.e., red blood cell count], and leukocytes [i.e., white blood cell count]) with 
differential (i.e., basophils, eosinophils, lymphocytes, monocytes, neutrophils) and 
platelet counts.
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, 
creatinine, and glucose.
Blood will be obtained for assessment of hematology and clinical chemistry parameters at 
screening/baseline, all study visits (i.e., pre- and perioperatively and daily while the 
patient is at the study site), and at study completion/termination. Hematology and clinical 
chemistry assessments will be performed on EDTA-anticoagulated whole blood and 
serum, respectively, at the central or local laboratory.
The urinalysis panel will consist of pH, protein, ketones, glucose, bilirubin, blood, 
urobilinogen, specific gravity by dipstick and microscopy if any findings are abnormal.
Urine will be obtained for assessment of urinalysis parameters at screening and at the 
postoperative hemostatic efficacy assessment, antibody testing visit, and End of Study 
visit.
For non-commercial use only

BAX 802
Page 69 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7.2 Viral Serology
Viral serology testing will include HIV-1 and HIV-2 antibody, HAV (immunoglobulin M 
[IgM] and total antibodies), hepatitis B surface antigen (HBsAg), hepatitis B surface 
antibody (HBsAb), hepatitis B core antibody (HBcAb), HCV antibody, and parvovirus 
B19 (IgM and immunoglobulin G [IgG] antibodies). The HIV and HCV titer will be 
confirmed by PCR for all subjects reported as HIV and HCV positive. All viral serology 
assessments will be performed at screening. Any positive HBsAg test will be repeated 
using a new blood sample.
12.7.3 Immunogenicity
Immunogenicity assessments will include anti-pFVIII and hFVIII binding (IgG and IgM) 
and inhibitory antibodies and anti-BHK binding antibodies.
Blood samples will be collected for the assay of anti-pFVIII and hFVIII binding and 
inhibitory antibodies and anti-BHK binding antibodies at the times indicated in Table 9
and Table 10.
All FVIII assays related to study subject management decisions by the Investigator will 
be performed at the Investigator’s local laboratory.
A central reference laboratory will perform assays (anti-pFVIII, anti-hFVIII, and 
anti-BHK) on samples taken at the times indicated in Table 9 and Table 10.
Binding antibodies to human and porcine FVIII (both IgG and IgM) and binding 
antibodies to BHK proteins will be analyzed using validated enzyme-linked 
immunosorbent assays (ELISAs) using a multi-tiered approach consisting of screening 
assay, titer determination and confirmation of specificity. 
 
 
 
The assessment of inhibitory antibodies to pFVIII and hFVIII will be determined using a 
Bethesda assay (with the Nijmegen modification if possible). Further details on blood 
collection, tube preparation and shipment will be provided in the Laboratory Manual.
For non-commercial use only

BAX 802
Page 70 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7.4 Assessment of Laboratory Values
12.7.4.1 Assessment of Abnormal Laboratory Values
The Investigator’s assessment of each laboratory value will be recorded on the CRF. For 
each abnormal laboratory value, the Investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the Investigator
will indicate if the value constitutes a new AE (see definition in Section 12.1, and record
the sign, symptom, or medical diagnosis on the AE CRF), is a symptom or related to a
previously recorded AE, is due to a pre-existing disease (described in Section 12.1.1.5), 
or is due to another issue that will be specified. If the abnormal value was not clinically
significant, the Investigator will indicate the reason, i.e., because it is due to a preexisting 
disease, due to a laboratory error, or due to another issue that will be specified.
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically
indicated. Any abnormal value that persists should be followed at the discretion of the 
Investigator.
12.7.5 Backup Samples and Biobanking
Backup samples taken and stored short-term may be used for re-testing, follow-up of an 
AE(s) or other test results (such as FVIII activity and antibody testing), and/or assay 
development.
After study testing is completed, the remaining samples may be stored in a coded form 
for no more than 2 years after final study report completion and then the samples will 
subsequently be destroyed.
For this study, no samples will be taken or stored long-term in a biobank for future 
analyses.
12.8 Vital Signs
Vital signs will include body temperature (°C or °F), respiratory rate (breaths/min), pulse 
rate (beats/min), and systolic and diastolic blood pressure (mmHg). Height (in or cm) 
measured once at screening, and weight (lb or kg) will also be collected. 
Vital signs will be measured at screening and within 30 minutes before and 
30 ±5 minutes after administration of IP, at each study visit, at any unscheduled 
assessments, and at study completion/termination. Blood pressure will be measured when 
subjects are in the supine position.
For non-commercial use only

BAX 802
Page 71 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Vital sign values are to be recorded on the CRF. For each abnormal vital sign value, the 
Investigator will determine whether or not to report an AE (see definition in Section 12.1
and record the medical diagnosis (preferably), symptom, or sign on the AE CRF). 
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
Investigator.
12.9 Karnofsky Performance Test
The Karnofsky Performance Test is a status scale (0 to 100) utilized to measure the level 
of activity and medical care requirements in subjects. It is an Investigator based 
assessment of patient status which evaluates the subjects’ ability to carry on normal life 
activities, as well as the symptoms of their disease.19 Subjects will be scored using this 
scale at screening.
12.10 Special Treatment Considerations
Patients will be screened for eligibility in the study as described in the 
inclusion/exclusion criteria (Section 9.1 and Section 9.2), and will be informed of the 
study specific restrictions and requirements of the study. Patients who are not willing to 
comply with the study requirements and restrictions of the study will not be eligible for 
enrollment.
All biological agents carry the risk of systemic allergic/hypersensitivity reactions. 
Clinical manifestations of these reactions may include, but are not limited to:

skin rash

pruritus (itching)

urticaria (hives)

angioedema (e.g., swelling of the lips and/or tongue)

anaphylactic reaction.
Proteins may also cause redness, itching, swelling, or pain locally at the infusion site.
Sometimes, these reactions can be life-threatening. Therefore, all patients should be 
closely monitored for signs or symptoms that could result from such reactions, educated 
on the signs or symptoms of these types of reactions, and instructed to contact the study 
site immediately if any of the symptoms are experienced following an injection. 
For non-commercial use only

BAX 802
Page 72 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If a patient experiences an acute allergic/hypersensitivity reaction after an injection of IP, 
he should be managed appropriately and given instruction to receive relevant supportive 
care. Additionally, for an event judged by the Investigator to be a potential systemic 
allergic/hypersensitivity reaction, blood samples will be collected for anti-pFVIII, anti 
hFVIII, and anti-BHK binding antibodies. Serious adverse events related to development 
or worsening of inhibitors are described in Section 12.1.1.1.1.
Patients who experience a potentially severe allergic reaction will be discontinued from 
study drug, they will complete an End of Study Visit, and will be monitored for 
stabilization, or resolution of the AE. Premedication to prevent allergic reactions will not 
be permitted as severe allergic reactions are an outcome measure for this study. 
For non-commercial use only

BAX 802
Page 73 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. STATISTICS
All details regarding the statistical analysis and the preparation of tables, listings, and 
figures will be described in the statistical analysis plan (SAP). 
13.1 Sample Size and Power Calculations
The total sample size for the study is 12 evaluable subjects, which includes at least 
12 surgeries/procedures in 12 evaluable male subjects (at least 5 major 
surgeries/procedures in 5 evaluable subjects) and at least 2 of the 12 subjects are 
adolescents (≥ 12 to < 18 years old). The sample size, as defined in the protocol, was 
chosen to provide sufficient evidence of safety and effectiveness for this indication and is 
not based on statistical considerations.
Evaluable subjects are defined as subjects who met all study entry criteria and who had at 
least 1 hemostatic efficacy assessment as per Section 8.4.1.
13.2 Analysis Sets
Classification into the analysis sets will be conducted prior to the database lock.
13.2.1 Safety Analysis Set
The safety analysis set (SAS) will be comprised of all subjects who received any amount 
of BAX 802.
13.2.2 Efficacy Datasets
13.2.2.1 Full Analysis Set 
The FAS will be comprised of all surgeries with at least 1 available hemostatic 
assessment.
13.2.2.2 Per-Protocol Analysis Set
The per-protocol (PPAS) analysis set will be comprised of all surgeries with evaluable 
ratings for all 3 perioperative hemostatic efficacy assessments, whose subjects met all 
study entry criteria and had no major protocol violations that might impact hemostatic 
efficacy assessments.
13.3 Handling of Missing, Unused, and Spurious Data
A subject who withdraws prior to the last planned observation in a trial period will be 
included in the analyses up to the time of withdrawal.
For non-commercial use only

BAX 802
Page 74 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
For surgeries with ≤2 missing hemostatic assessments that did not necessitate rescue 
therapies, the rating of “fair” will be imputed for the missing assessment. These surgeries 
will be included in the FAS.
13.4 Methods of Analysis
For qualitative parameters, the population size (N for sample size and n for available 
data) and the proportion (of available data) for each class of parameters will be presented. 
Quantitative parameters will be summarized by the population size (N for sample size 
and n for available data), mean, standard deviation, median, minimum, and maximum 
values.
13.4.1 Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy 
assessed intraoperatively and at postoperative Day 1 (postoperative period, i.e., from end 
of surgery to 24 ±6 hours post-surgery) by the surgeon and perioperatively at 24 to 72 
hours after the last perioperative treatment dose of BAX 802 or discharge (whichever is 
earlier) by the Investigator (hemophilia physician), and where possible, by both the 
Investigator and the operating surgeon (assessment by both is strongly recommended), 
and will be the sum of intraoperative, postoperative, and perioperative GHEA scores as
rated “excellent”, “good”, “fair” or “none”. In cases where there are differing 
assessments, the Investigator’s assessment will be used.
If discharge is delayed for a reason other than surgery related bleeding (e.g., pneumonia), 
an assessment at 24 to 78 hours after last perioperative treatment dose of BAX 802 will 
ensure that the overall perioperative assessment is completed close to the last 
administered study drug dose. Wherever possible (except for intraoperative assessment), 
bleeding should be assessed by both operating surgeon and Investigator. To achieve the 
hemostatic efficacy success criteria, the study needs to achieve a ≥70% rate of 
hemostatic efficacy assessments with an “excellent” or “good” outcome in at least 
12 procedures. 
Hemostatic efficacy success is defined as an “excellent” or “good “outcome for ≥70% of 
hemostatic efficacy assessments.
Due to the possibility of a subject undergoing multiple surgeries, the statistical 
analysis of the primary outcome measure will be reported on the by-surgery level 
(i.e., not by the number of subjects). In cases where two or more surgical procedures 
are performed in the same intraoperative settings (under the same anesthesia, 
e.g., bilateral knee replacement) the surgery will be counted as one surgery. 
For non-commercial use only

BAX 802
Page 75 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Blood loss assessment from those surgeries will be assessed as one. In the event that the 
subject is planning to have additional surgery in the future, they will need to complete the 
study and be re-screened again (if > 3 months from the screening) to ensure that they 
continue to meet the eligibility criteria.
Point estimates and corresponding 2-sided exact Clopper-Pearson confidence intervals 
(CIs) at the 95% confidence level will be calculated for the rate of hemostatic efficacy 
assessments with excellent/good outcome for descriptive purposes.
The proportion of all surgeries and of all major surgeries with hemostatic success will be 
reported along with exact 95% CIs. A treatment success will be defined as a rating of 
excellent or good.
The primary efficacy analysis will be based on the FAS population. As a supportive 
analysis, the same analyses will also be carried out on the PPAS population.
A sensitivity analysis based on the first surgery will be performed if more than 20% of 
subjects have multiple surgeries. Any blood loss which is considered as unrelated 
bleeding (defined as any bleeding occurring at a different anatomical site other than the 
surgery site during the postoperative period, see Section 11.2.5) will not be taken into 
account for while making assessment of hemostatic efficacy for the primary efficacy 
measure.
13.4.2 Secondary Outcome Measures 
13.4.2.1 Secondary Hemostatic Efficacy Analysis
Secondary outcome measures will be reported at the surgery level rather than the subject 
level. Descriptive statistics will be used to summarize the actual blood loss and 
transfusion requirements. 
The summary of average daily and total weight-adjusted doses (average through 
postoperative 24 to 72 hours after last perioperative treatment dose of BAX 802 or 
discharge [whichever is earlier]) of BAX 802 per subject as well as the occurrence of 
bleeding episodes will be provided using descriptive statistics. 
The proportion of major surgeries with good or excellent hemostatic score together with 
its 2-sided 95% CI will be reported for descriptive purposes.
The secondary efficacy analysis will be performed on the FAS only.
For non-commercial use only

BAX 802
Page 76 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.2.2 Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by presenting the number and proportion of subjects 
having any AE, having an AE in each system organ class, and having each individual AE 
as reported by preferred term. In the summaries, AEs will be counted only once per 
patient. If a patient reports the same AE more than once, it will be counted with its worst 
severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the 
number of IP-related AEs will be tabulated and subcategorized for thrombo-embolic
events, inhibitory and total binding antibodies (IgG and IgM) to pFVIII and hFVIII, and 
binding antibodies to BHK proteins.
A listing of all AEs will be presented by subject identifier, age, preferred term, and 
reported term of the AE, duration, severity, seriousness, action taken, outcome, causality 
assessment, onset date, stop date, and medication or non-drug therapy to treat the AE. An 
overview table for AEs will be provided, presenting the number of AEs, the number of 
subjects with AEs and the corresponding percent of subjects in total, and by seriousness 
and relationship to study treatment. An additional summary table will present the total 
number of (mild, moderate, severe) AEs by system organ class and preferred term with 
relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. 
Descriptive statistics of changes from baseline (prior to BAX 802 loading dose before the 
surgery) by study visits will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. 
Furthermore, laboratory abnormalities will be analyzed by shift tables where each subject 
will be counted only once with the worst grade in the summary tables. 
All laboratory data will be listed with abnormal values.
Vital signs assessments as well as the corresponding changes from baseline will be 
summarized descriptively at each scheduled or unscheduled assessment.
The safety analysis will be based on the SAS.
For non-commercial use only

BAX 802
Page 77 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.1 Exploratory Outcome Measures 
 
.
 
 
.
 
. 
 
 
.
Further details will be included in the SAP.
13.5 Planned Interim Analysis of the Study
No interim analyses are planned for this study.
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The Investigator/study site will cooperate and provide direct access to study documents 
and data, including source documentation for monitoring by the study monitor, audits by
the sponsor or sponsor’s representatives, review by the Institutional Review Board (IRB) 
or Ethics Committee (EC), and inspections by applicable regulatory authorities, as 
described in the Clinical Trial Agreement (CTA). If contacted by an applicable regulatory
authority, the Investigator will notify the sponsor of contact, cooperate with the authority, 
provide the sponsor with copies of all documents received from the authority, and allow 
the sponsor to comment on any responses, as described in the CTA.
For non-commercial use only

BAX 802
Page 78 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The Investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable national and local regulatory requirements 
as described in the CTA. The Investigator is ultimately responsible for the conduct of all 
aspects of the study at the study site and verifies by signature the integrity of all data 
transmitted to the sponsor. The term “Investigator” as used in this protocol as well as in 
other study documents, refers to the Investigator or authorized study personnel that the 
Investigator has designated to perform certain duties. Sub-Investigators or other 
authorized study personnel are eligible to sign for the Investigator, except where the 
Investigator’s signature is specifically required.
15.1.1 Investigator Report and Final Clinical Study Report
The Investigator, or coordinating Investigator(s) for multicenter studies, will sign the 
clinical study report. The coordinating Investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the Investigator and study site personnel understand 
all requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an Investigator. Training may be provided at an Investigator’s meeting, 
at the study site, and/or by instruction manuals. In addition, the study monitor will be 
available for consultation with the Investigator and will serve as the liaison between the 
study site and the sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts 
the study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory
guidelines/requirements. The Investigator will permit the study monitor to visit the study
site at appropriate intervals, as described in the CTA. Monitoring processes specific to 
the study will be described in the clinical monitoring plan.
15.4 Safety Monitoring
The safety of the subjects in this study shall be monitored by an external DSMB 
comprised of experts in the field of hemophilia research and clinical care.
For non-commercial use only

BAX 802
Page 79 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The DSMB will review safety data at predefined intervals and make recommendations to 
the study team on study conduct including dose escalation and modifications to study 
plan. Details of the composition and responsibilities of the DSMB will be provided in a 
DSMB charter.
15.5 Auditing
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory
guidelines/requirements. The Investigator will permit auditors to visit the study site, as 
described in the CTA. Auditing processes specific to the study will be described in the 
audit plan.
15.6 Non-Compliance with the Protocol
The Investigator may deviate from the protocol only to eliminate an apparent immediate 
hazard to the subject. In the event(s) of an apparent immediate hazard to the subject, the 
Investigator will notify the sponsor immediately by phone and confirm notification to the 
sponsor in writing as soon as possible, but within 1 calendar day after the change is 
implemented. The sponsor (Baxalta) will also ensure the responsible EC and relevant 
competent authority is notified of the urgent measures taken in such cases according to 
local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the sponsor may terminate the Investigator’s participation. The sponsor will 
notify the EC and applicable regulatory authorities of any Investigator termination.
15.7 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments. Local 
laboratories are requested to provide their laboratory specifications for each assay used.
For non-commercial use only

BAX 802
Page 80 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16. ETHICS
16.1 Subject Privacy
The Investigator will comply with applicable subject privacy regulations/guidance as 
described in the CTA.
16.2 Ethics Committee and Regulatory Authorities
Before patients participate in this study, the protocol, informed consent form, any
promotional material/advertisements, and any other written information will be reviewed 
and approved/given favorable opinion by the EC and applicable regulatory authorities. 
The IB will be provided for review. The EC’s composition or a statement that the EC’s 
composition meets applicable regulatory criteria will be documented. The study will 
commence only upon the sponsor’s receipt of approval/favorable opinion from the EC 
and, if required, upon the sponsor’s notification of applicable regulatory authority(s) 
approval, as described in the CTA.
If the protocol or any other information given to the subject is amended, the revised 
documents will be reviewed and approved/given favorable opinion by the EC and 
applicable regulatory authorities, where applicable. The protocol amendment will only be 
implemented upon the sponsor’s receipt of approval and, if required, upon the sponsor’s 
notification of applicable regulatory authority(s) approval.
16.3 Informed Consent
Investigators will choose patients for participation considering the study eligibility
criteria. The Investigator will exercise no selectivity so that no bias is introduced from 
this source.
All patients and/or their legally authorized representative must sign an ICF before 
entering into the study according to applicable national and local regulatory requirements 
and ICH GCP. An assent form may be provided and should be signed by patients less 
than 18 years of age. Before use, the ICF will be reviewed by the sponsor and approved 
by the EC and regulatory authority(s), where applicable, (see Section 16.2). The ICF will 
include a comprehensive explanation of the proposed treatment without any exculpatory
statements, in accordance with the elements required by ICH GCP and applicable 
national and local regulatory requirements. Patients or their legally authorized 
representative(s) will be allowed sufficient time to consider participation in the study. By
signing the ICF, patients or their legally authorized representative(s) agree that they will 
complete all evaluations required by the study, unless they withdraw voluntarily or are 
terminated from the study for any reason.
For non-commercial use only

BAX 802
Page 81 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The sponsor will provide to the Investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The ICF will be 
updated, if necessary. This new information and/or revised ICF that has been approved by 
the applicable EC and regulatory authorities, where applicable, will be provided by the 
Investigator to the subjects who consented to participate in the study (see Section 16.3).
For non-commercial use only

BAX 802
Page 82 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The Investigator will comply with the confidentiality policy as described in the CTA. 
17.2 Study Documentation and Case Report Forms
The Investigator will maintain complete and accurate paper format study documentation 
in a separate file. Study documentation may include information defined as “source data” 
(see Section 8.8), records detailing the progress of the study for each subject, signed 
informed consent forms, correspondence with the EC and the study monitor/sponsor, 
screening information, CRFs, SAERs, laboratory reports (if applicable), and data 
clarifications requested by the sponsor.
The Investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry 
will be crossed out entirely, remaining legible; and 2) each correction must be dated and 
initialed by the person correcting the entry; the use of correction fluid and erasing are 
prohibited.
The Investigator is responsible for the procurement of data and for the quality of data 
recorded on the CRFs. CRFs will be provided in electronic form.
If electronic format CRFs are provided by the sponsor, only authorized study site 
personnel will record or change data on the CRFs. If data is not entered on the CRFs 
during the study visit, the data will be recorded on paper, and this documentation will be 
considered source documentation. Changes to a CRF will require documentation of the 
reason for each change. An identical (electronic/paper) version of the complete set of 
CRFs for each subject will remain in the Investigator file at the study site in accordance 
with the data retention policy (see Section 17.3).
The handling of data by the sponsor, including data quality assurance, will comply with 
regulatory guidelines (e.g., ICH GCP) and the standard operating procedures of the 
sponsor. Data management and control processes specific to the study will be described 
in the data management plan.
17.3 Document and Data Retention 
The Investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention 
policy, as described in the Clinical Study Agreement.
For non-commercial use only

BAX 802
Page 83 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
18. FINANCING AND INSURANCE
The Investigator will comply with Investigator financing, Investigator/sponsor insurance, 
and subject compensation policies, if applicable, as described in the CTA.
19. PUBLICATION POLICY
The Investigator will comply with the publication policy as described in the CTA. 
For non-commercial use only

BAX 802
Page 84 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. SUPPLEMENTS
20.1 Procedures per Study Period
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502
1. Screening
Written Informed Consent must be obtained prior to any study-related procedures
Screening activities should be performed within 45 days prior to the planned elective surgery.
The following screening procedures are required:

Eligibility evaluation (review of inclusion/exclusion criteria)

Hemophilia history, bleeding episode history, history of aPCC or rFVIIA usage for a year prior to 
screening

Relevant medical and surgical history and all medications taken 3 months prior to screening

Review of concomitant medications/non-drug therapies

Physical examination (see Section 12.6)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body weight 
and height; see Section 12.8)

Karnofsky performance test assessment (see Section 12.9)

Clinical laboratory assessments (see Table 10).
For non-commercial use only

BAX 802
Page 85 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502
2. Preoperative Procedures
Subjects will return to the study site prior to their scheduled surgery as instructed by site staff. Subjects will 
undergo the following procedures:
Prior to surgery
The following procedures should be performed before surgery and must be available by at the latest 2 hours 
before the start of surgery:

Accurate prediction of volume of expected blood loss intraoperatively (from completion of the 
procedure until approximately 24 hours post-surgery) and for the overall perioperative time period 
(up to 24 to 72 hours after the last perioperative treatment dose of BAX 802 or discharge), which is 
to be timestamped into the source documentation and/or blood loss form prior to the surgery.
Loading Dose and Post Dosing Laboratory Assessment
Within 1 to 2 hours before initiating surgery, the subject will receive a loading dose of BAX 802 to raise 
the plasma level of FVIII to ≥80% for major and to ≥50% for minor surgical, dental and invasive 
procedures.
Subjects will undergo the following procedures:

Prior to BAX 802 loading dose:

Record AEs, concomitant medications, and non-drug therapy use

Physical examination, vital signs (pulse rate, respiratory rate, blood pressure, and temperature) 
and weight

Laboratory Assessments including:
o
Hematology (without differential but including platelets)
o
Clinical chemistry  
o
Within 30 minutes before loading dose, blood draw for:

FVIII activity 

BAX 802 loading dose:

Loading dose of BAX 802 to raise the plasma level of FVIII to ≥80% of normal for major and 
to ≥50% for minor surgical, dental and invasive procedures. It will be administered within 1 to
2 hours prior to surgery (prior to incision/intubation). 

After BAX 802 loading dose:

Laboratory assessment of FVIII activity: 30 ±5 minutes after infusion of the loading dose

Vital signs (pulse, respiratory rate, blood pressure and temperature) will be recorded 
30 ±5 minutes after infusion

Confirmation that FVIII is adequate just prior to intubation/incision. Administration of 
additional dose of BAX 802, if required. If another dose of BAX 802 is necessary, an additional 
post-infusion FVIII activity determination must be performed 30 ±5 minutes following the 
infusion.

All samples taken through 6 hours post-infusion will be collected from an extremity other than 
that used for the infusion of study product. Thereafter, either extremity may be used to obtain 
samples.
The surgery may begin only if FVIII is in target range (Table 5 and Section 8.7.3.3.2).
Throughout: Monitoring of AEs and concomitant medication and non-drug therapy use.
For non-commercial use only

BAX 802
Page 86 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502
3. Intraoperative Procedures (end of surgery = Day 0)
During the surgical procedure:

Record AEs and concomitant medication and non-drug therapy use

Record blood product usage, including salvaged blood, packed red blood cells (pRBC), platelets, 
and other blood products. 

Administer additional BAX 802 infusions according to the dosing regimen (Table 5) 

Record intraoperative blood loss and transfusion requirements
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary, the 
subject will subsequently be withdrawn from this BAX 802 surgery study and be considered a treatment 
failure. 
After the surgical procedure:

Record the volume of blood loss during surgery and amount of total blood product usage, including 
salvaged blood, packed red blood cells (pRBCs), platelets, and other blood products

Assess intraoperative hemostatic efficacy (Global Hemostatic Efficacy Assessment, GHEA1, 
Table 2) (at the end of surgery) 

Take sample for FVIII activity immediately after surgery completion, with dose adjustments as 
necessary on the day of surgery (see Section 10.5)

Take sample for FVIII activity within preferably 4 to 6 hours following surgery, with dose 
adjustments as necessary on the day of surgery (see Section 10.5)
If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary (see 
Section 10.5), the subject will subsequently be withdrawn from this BAX 802 surgery study and considered 
a treatment failure.
For non-commercial use only

BAX 802
Page 87 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502
4. Postoperative Procedures (Day 1 to discharge)

For subjects undergoing major surgery: keep pre-infusion FVIII levels at least at 80% of normal for 
the first postoperative 72 hours and at least at 50% during postoperative Day 4 to Day 7. It is 
recommended that the FVIII levels do not fall below 30% from Day 8 until discharge.

For subjects undergoing minor surgery: keep pre-infusion FVIII levels at least at 50% of normal for 
the first postoperative 72 hours. It is recommended that the FVIII levels do not fall below 30% from 
Day 4 until discharge.
From Postoperative Day 1 (i.e., the day following the day of the surgical/invasive procedure), 
and daily until discharge the following assessments will be performed:

Record AEs and concomitant medication and non-drug therapy use

Record blood loss on a daily basis and at drain removal, if applicable

Record transfusion requirements

GHEA:
o
GHEA2 (Table 3): assessment of postoperative hemostatic efficacy of BAX 802
performed at Day 1 by the operating surgeon/Investigator
o
GHEA3 (Table 4): assessment of perioperative hemostatic efficacy of BAX 802 at 24 to 
72 hours after the last perioperative treatment dose of BAX 802 or discharge (whichever 
is earlier) performed by the Investigator, and where possible, also by the operating 
surgeon
If a subject leaves the facility on the day of the surgery/invasive procedure, it is required to 
have a site visit the next day (Day 1) and at 24 to 72 hours after the last perioperative treatment 
dose of BAX 802 to perform the assessments of postoperative (GHEA2) and perioperative 
(GHEA3) hemostatic efficacy, respectively.

Perform physical examination and vital signs (pulse, respiratory rate, blood pressure and 
temperature) on Days 1, 2, 3, and 7 post surgery (if a subject remains admitted). 

Blood draws for FVIII activity determination and hematology should be performed coincident 
with an early morning dose to the greatest extent possible.

FVIII activity assays at the local and the central laboratories as per Section 8.7.3.3.3. Additional 
BAX 802 doses will be administered as per Table 5. FVIII activity assays pre infusion (within 
30 minutes) and post infusion (30 ±5 minutes) for each IP administration, and at other time 
points as deemed necessary by the surgeon or Investigator throughout the study 
o
1-stage clotting and chromogenic for the central laboratory
o
1-stage clotting for local laboratories

Samples for laboratory testing will be taken daily during Day 1 to 7 post-surgery and then 
subsequently once weekly:
o
Hematology
o
Clinical chemistry

If the subject has excessive or unexplained bleeding, blood draws for FVIII activity. Treat by 
whatever means necessary until adequate hemostasis is achieved. If rescue medications become 
necessary, the subject will subsequently be withdrawn from this BAX 802 surgery study and 
considered a treatment failure.

If the subject is discharged from surgical facility on the day of the procedure, he should attend the 
site on Day 1 to perform the postoperative hemostatic efficacy assessment (Day 1 assessment) and 
the overall perioperative assessment. In this case, physical examination, vital signs, laboratory 
assessments, adverse events, and concomitant medications must also be assessed. If the subject is 
discharged from surgical facility after Day 1 but prior to the overall perioperative assessment, he 
should return to the site for that assessment as well as the required physical examination, vital 
signs, laboratory assessments, adverse events, and concomitant medications assessments. In cases 
where the Discharge Visit would occur within 3 days of the End of Study Visit, the respective visits 
may be done as a single visit.
For non-commercial use only

BAX 802
Page 88 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8: Summary of Required Procedures for Baxalta Clinical Study 241502
5. Perioperative hemostatic efficacy assessment (24 to 72 hours after last perioperative treatment 
dose of BAX 802)/Discharge Visit/End of Study [EOS] Visit (42 ± 7 days of last dose of BAX 802)
The perioperative hemostatic efficacy assessment will be performed 24 to 72 hours after the last 
perioperative treatment dose of BAX 802 if subject has not been discharged by then. The Discharge Visit 
will be performed when the subject is discharged, and the EOS Visit will be performed 42 ± 7 days 
following the last dose of IP. In cases where the Discharge Visit would occur within 3 days of the EOS 
Visit, the respective visits will be done as a single visit.
Procedures to be performed for each subject at perioperative hemostatic efficacy 
assessment/Discharge Visit/EOS Visit:

Assessment of blood loss

Assessment of transfusion requirements

Review of concomitant medications/non-drug therapies

physical examination 

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body 
weight)

Clinical laboratory assessments (Table 10)

Immunogenicity assays:

 

Anti-BHK binding antibody titers
6. Antibody Testing Visit
A visit will be performed between 7 to 14 days after the subject is discharged. Study procedures will be 
performed as per Table 9 and blood samples will be collected for antibody testing and other tests as per 
Table 10. De novo or clinically significant increases in antibodies will require a confirmatory blood sample 
collection 7 to 14 days after the initial positive result.
Procedures to be performed for each subject at Antibody Testing Visit:

Immunogenicity assays:

 
(Note: these will be performed only if at least 72 hours must have elapsed 
since the previous BAX 802 administration)
Anti-BHK binding antibody titers
Unrelated Bleeding Episodes During the Postoperative Period:
An unrelated bleeding episode is defined as any bleeding occurring at a different anatomical site than the 
surgery site during the postoperative period. Refer to Section 11.2.5, Table 9, and Table 10.
For non-commercial use only

BAX 802
Page 89 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.2 Study Flow Chart
Figure 2: Visit Schedule
                                                                                                                                                                                                
                                                                                                                                                                                        45 days 
                                                                                                                                                                         1 day
                                                                                                                                                                      variable
                                                                                                                                                                      42±7 days post last dose
Enrollment Screening
Pre-op procedures
Surgery (Day 0)
Post-op procedures (Day 1 and daily 
until discharge)
EOS visit + Inhibitor assessment
I/E criteria confirmed, including anti-
human and anti-porcine FVIII titer 
assessment
Discharge
For non-commercial use only

BAX 802
Page 90 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.3 Schedule of Study Procedures and Assessments
Table 9: Schedule of Study Procedures and Assessments
Period
Screening Preoperative Intraoperative
Postoperative
End of Study
Visit
Screening Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures; 
until subject is 
discharged
Day 14 ±3 or 
Discharge (whichever 
is earlier) proceduresa
Antibody Testing 
Visitb
End of Study 
Visitc/ 
Discharge 
proceduresa
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During surgery
Day 1 and daily 
thereafter until 
discharge
24 to 72 hours after 
last perioperative 
treatment dose of 
BAX 802 or discharge 
(whichever is earlier)j
7 to 14 days after 
last perioperative 
treatment dose of 
BAX 802
Discharge 
daya / EOSc
42 ± 7 days 
post-surgery
Eligibility criteria, including 
medical historyd
X
Prediction of intraoperative 
blood losse
X
Medications and non-drug 
therapies
X
X
X
X
X
X
X
Physical examination
X
X
Xf (as required)
X
X
X
Adverse events
X
X
X
X
X
X
Laboratory assessmentsg
X
Xi
X
Xl
X
X
X
Vital signsh
X
X
X
X
X
X
X
Karnofsky Performance Test
X
Approved FVIII maintenance 
plan
X
IP treatment
X (loading 
dose; Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
For non-commercial use only

BAX 802
Page 91 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 9: Schedule of Study Procedures and Assessments
Period
Screening Preoperative Intraoperative
Postoperative
End of Study
Visit
Screening Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures; 
until subject is 
discharged
Day 14 ±3 or 
Discharge (whichever 
is earlier) proceduresa
Antibody Testing 
Visitb
End of Study 
Visitc/ 
Discharge 
proceduresa
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During surgery
Day 1 and daily 
thereafter until 
discharge
24 to 72 hours after 
last perioperative 
treatment dose of 
BAX 802 or discharge 
(whichever is earlier)j
7 to 14 days after 
last perioperative 
treatment dose of 
BAX 802
Discharge 
daya / EOSc
42 ± 7 days 
post-surgery
Hemostatic Efficacy 
Assessments (GHEA1, 
GHEA2, and GHEA3)
GHEA1 at the 
end of surgery 
as per Table 2
GHEA2 at 12 to 
24 hours (Day 1) 
as per Table 3
GHEA3 at 24 to 72 
hours after the last 
perioperative treatment 
dose of study drug is 
administered or 
discharge (whichever is 
earlier), as per Table 4j
Transfusion requirements and 
blood lossk
X
X
X
X
Procedures for Unrelated/Surgical Site Bleeding Episodes During the Postoperative Period (see Sections 11.2.3 and 11.2.5)m
Medications and non-drug 
therapies
X
Laboratory assessments
Refer to Table 10
IP treatment
Refer to Table 6
Vital signsh
X
Hemostatic Efficacy 
Assessments
At 24 ±2 hours after the initiation of treatment and at the resolution of bleed (if not resolved 
within 24 hours) using a 4-point efficacy rating scale (Table 7)
Transfusion requirements and 
blood lossk
X
Continued on Next Page
For non-commercial use only

BAX 802
Page 92 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
Key: EOS = End of Study Visit; OR = operating room
a
In cases where the Discharge Visit would occur within 3 days of the End of Study Visit, the respective visits may be done as a single visit. Procedures 
differ on Discharge from the other postoperative days only with regard to laboratory assessments (see Table 10).
b
The Antibody Testing Visit is required. Any de novo (> 0.6 BU) or significantly increased (> 10 BU) results will require confirmatory blood 
assessments an additional 7 to 14 days later, which is to include the procedures identified here with data recorded as an unscheduled visit.
c
The End of Study Visit also applies to subjects who withdraw or discontinue prematurely. The EOS visit date must be at least 3 days after the most 
recent FVIII infusion to ensure that the requirement of a 72-hour washout period is met.
d
Occurs prior to any study-specific procedures; includes hemophilia history, bleeding episode history, history of aPCC or rFVIIA usage for a year 
prior to screening.
e
Preoperative prediction of expected blood loss for a subject with severe hemophilia A with inhibitors and a comparable healthy individual with the 
same demographic characteristics will be estimated and documented as per Section 11.2.1. This could also be performed days/weeks before the surgery, 
during the screening period.
f
Perform physical examination and vital signs (pulse rate, respiratory rate, blood pressure and temperature) on Days 1, 2, 3, and 7 post surgery (if a 
subject remains admitted).
g
For laboratory assessments, see Table 10.
h
Vital signs will include body temperature, pulse rate, blood pressure, respiratory rate, and weight. Blood pressure will be measured when subjects are 
in the supine position. Height, measured once at Screening, will also be collected. Vital signs will be measured at 30 minutes before and 
30 ± 5 minutes after administration of IP.
i
Within 30 minutes pre-dose and 30 ±5 minutes post-dose for FVIII activity.
j
If the subject is discharged from surgical facility on the day of the procedure, he should return to the site on Day 1 to perform the postoperative 
hemostatic efficacy assessment (Day 1 assessment) and the overall peri-operative assessment. In this case, physical examination, vital signs, laboratory 
assessments, adverse events, and concomitant medications/non-drug therapies must also be assessed. If the subject is discharged from surgical facility 
after Day 1 but prior to the overall peri-operative assessment, he should return to the site for that assessment as well as the required physical 
examination, vital signs, laboratory assessments, adverse events, and concomitant medications assessments. See footnote “a” for guidance on the 
combining of visits and assessments that fall within a 72 hour period.
k
Record blood loss on a daily basis and at drain removal; record blood product usage, including salvaged blood, packed red blood cells (pRBC), 
platelets, and other blood products. 
l
Blood draws for FVIII activity determination and hematology should be performed coincident with an early morning dose to the greatest extent 
possible. Samples for laboratory testing (hematology and clinical chemistry) will be taken daily until discharge from Day 1 through 7 post-surgery and 
then subsequently once weekly. 
m
May also be collected as an unscheduled visit.
For non-commercial use only

BAX 802
Page 93 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.4 Clinical Laboratory Assessments
Table 10: Clinical Laboratory Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Visit
Screen
Prior to 
surgery
Surgery to 
wound closure 
(Day 0)
Daily hospital 
visita
Perioperative 
hemostatic efficacy 
assessment
Antibody 
Testing Visitb
Discharge, 
post 
treatment, 
and/or End 
of Study 
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
In OR
Day 1 and 
daily 
thereafter to 
discharge
24 to 72 hours after 
last perioperative 
treatment dose of 
BAX 802 or 
discharge 
(whichever is 
earlier)a
7-14 days 
after last 
perioperative 
treatment 
dose of 
BAX 802
Discharge 
daya / EOSc
42 ± 7 days 
post dose
FVIII activity 
(clotting and
chromogenic assay 
at central laboratory; 
clotting assay at 
local laboratory)
Citrated 
plasma
C
L and C within 
30 minutes 
before loading 
dose, then 
30 ±5 minutes 
after loading 
dosed
Optional 
sampling, as 
deemed necessary: 
L and C
Also, if subject 
has excessive or 
unexplained 
bleeding
L and Ce
L and C
L and C
PT and aPTT
Citrated 
plasma
C and L
Chemistryf
Serum
C
L and C
(L)
L
Daily Days 1 to 7
C (L)
C (L)
C (L)
Hematology
Whole 
blood
Cg
Lh
(L)
L
Daily Days 1 to 7
C (L)
C (L)
C (L)
Urinalysis
Urine
C
C
C
C
Viral serologyi
Serumj
C
For non-commercial use only

BAX 802
Page 94 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 10: Clinical Laboratory Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Visit
Screen
Prior to 
surgery
Surgery to 
wound closure 
(Day 0)
Daily hospital 
visita
Perioperative 
hemostatic efficacy 
assessment
Antibody 
Testing Visitb
Discharge, 
post 
treatment, 
and/or End 
of Study 
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
In OR
Day 1 and 
daily 
thereafter to 
discharge
24 to 72 hours after 
last perioperative 
treatment dose of 
BAX 802 or 
discharge 
(whichever is 
earlier)a
7-14 days 
after last 
perioperative 
treatment 
dose of 
BAX 802
Discharge 
daya / EOSc
42 ± 7 days 
post dose
 
 
 
 
Citrated 
plasma
Cg
C
C
C
Anti-BHK binding 
Antibody titers
Citrated 
plasma
C
C
C
C
Laboratory Assessments for Unrelated Bleeding/Surgical Site Episodes During the Postoperative Period (see Section 11.2.5)k
FVIII activity 
(clotting and
chromogenic assay 
at central laboratory; 
clotting assay at 
local laboratory)
Citrated 
plasma
Refer to Section 11.2.5
Optional sampling, as deemed necessary: L and C
Continued on Next Page
For non-commercial use only

BAX 802
Page 95 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
Key: C = central laboratory; EOS = End of Study Visit; L = local laboratory; (L) = local testing optional, to aid in clinical management of patients.
a
In cases where the Discharge Visit would occur within 3 days of the End of Study Visit, the respective visits will be done as a single visit.
b
The Antibody Testing Visit is required. Any de novo (> 0.6 BU) or significantly increased (> 10 BU) results will require confirmatory blood 
assessments an additional 7 to 14 days later, which is to include the procedures identified here with data recorded as an unscheduled visit.
c
The End of Study Visit also applies to subjects who withdraw or discontinue prematurely.
d
It is recommended that the surgery starts after FVIII levels have achieved target levels. If FVIII activity post loading dose is close to the target level, a 
supplement dose of BAX 802 should be administered without further delaying the surgery. If FVIII activity post loading dose is not close to the target 
level, a supplement dose of BAX 802 should be administered and surgery delayed until FVIII levels have achieved target levels or are in close range.
e
FVIII activity should be monitored postoperatively as per instructions in Table 5 and Section 8.7.3.3.3.
f
Sodium, potassium, chloride, bicarbonate, protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and 
glucose.
g
Hematology and antibody testing should be performed during screening at least 2 weeks before the planned surgery day as hematocrit and 
anti-pFVIII inhibitor titer values are required for loading dose calculation.
h
Hematology, without differential but including platelets.
i
HIV-1 and HIV-2 antibody, HAV (IgM and total antibodies), HBsAg, HBsAb, HBcAb, HCV Ab, and parvovirus B19 (IgM and IgG antibodies). 
CD4 for HIV positive patients and HCV-RNA or HIV-RNA for confirmatory testing of HIV or HCV positive results, respectively.
j
Citrated plasma for HCV-RNA or HIV-RNA confirmatory testing.
k
May also be collected as an unscheduled visit.
For non-commercial use only

BAX 802
Page 96 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.5 Global Efficacy Assessments Scores
Table 11: Combinations of Individual Efficacy Assessments
(GHEA1, GHEA2, and GHEA3) and GHEA Score
Individual 
Assessment Scores
(GHEA1, GHEA2, and GHEA3)
GHEA
3 3 3
Excellent
3 3 2
Excellent
3 2 2
Excellent
3 3 1
Good
3 2 1
Good
3 1 1
Good
2 2 2
Good
2 2 1
Good
2 1 1
Fair
1 1 1
Fair
3 3 0
None
3 2 0
None
3 1 0
None
3 0 0
None
2 2 0
None
2 1 0
None
2 0 0
None
1 1 0
None
1 0 0
None
0 0 0
None
For non-commercial use only

BAX 802
Page 97 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.6 Definitions
20.6.1 Joint Bleeds
Features of an acute joint bleed include some or all of the following: ‘aura’, pain, 
swelling, warmth of the skin over the joint, decreased range of motion and difficulty in 
using the limb compared with baseline or loss of function. 
The earliest clinical signs of a joint bleed are increased warmth over the area and 
discomfort with movement, particularly at the ends of range.
Later symptoms and signs include pain at rest, swelling, tenderness, and extreme loss of 
motion.
In patients with advanced arthropathy it may be difficult to distinguish pain-related 
arthritis from that associated with an acute bleed. Rapid resolution of pain following 
infusion of factor concentrates (typical of an acute hemarthrosis) or improvement of pain 
associated with activity soon after a period of rest (typical of chronic arthritis) can help 
distinguish between the two.
20.6.2 Muscle Bleeds
Muscle bleeds can occur in any muscle of the body, usually from a direct blow or a 
sudden stretch. A muscle bleed is defined as an episode of bleeding into a muscle, 
determined clinically and/or by imaging studies, generally associated with pain and/or 
swelling and functional impairment over baseline.
For further definitions of central nervous system, gastrointestinal, and abdominal 
hemorrhages see the Guidelines for the management of hemophilia from the WFH.5,20
For non-commercial use only

BAX 802
Page 98 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES
1.
Coppola A, Di Capua M, Di Minno MND, et al. Treatment of hemophilia: A 
review of current advances and ongoing issues. J Blood Med. 2010;1:183-195.
2.
Janbain M, Leissinger CA, Kruse-Jarres R. Acquired hemophilia A: emerging 
treatment options. J Blood Med. 2015;6:143-150.
3.
Mansouritorghabeh H. Clinical and laboratory approaches to hemophilia A. Iran J 
Med Sci. 2015;40(3):194-205.
4.
Berntorp E, Shapiro A, Astermark J, et al. Inhibitor treatment in haemophilias A 
and B: summary statement for the 2006 international consensus conference. 
Haemophilia. 2006;12 Suppl 6:1-7.
5.
World Federation of Hemophilia Treatment Guidelines Working Group. Guidelines 
for the management of hemophilia 2nd Edition. Guidelines for the management of 
hemophilia 2nd Edition; 2012:80. Web Link: 
http://www1.wfh.org/publication/files/pdf-1472.pdf
6.
Santagostino E, Escobar M, Ozelo M, et al. Recombinant activated factor VII in the 
treatment of bleeds and for the prevention of surgery-related bleeding in congenital 
haemophilia with inhibitors. Blood Rev. 2015;29 Suppl 1:S9-S18.
7.
Valentino LA, Cooper DL, Goldstein B. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX. Haemophilia 589. Vol. 17. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX; 2011:11-579. Web Link: 
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2516.2010.02460.x/epdf
For non-commercial use only

BAX 802
Page 99 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.
Kempton CL, White GC, II. How we treat a hemophilia A patient with a factor VIII 
inhibitor. Blood. 2009;113(1):11-17.
9.
Kasper CK. Effect of prothrombin complex concentrates on factor VIII inhibitor 
levels. Blood. 1979;54:1358-1368.
10.
Young G, Sørensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS. 
Thrombin generation and whole blood viscoelastic assays in the management of 
hemophilia: current state-of-art and future perspectives. Blood. 2013;121(11):1944-
1950.
11.
Kempton CL, Abshire TC, Deveras RA, et al. Pharmacokinetics and safety of OBI-
1, a recombinant B domain-deleted porcine factor VIII, in subjects with 
haemophilia A. Haemophilia. 2012;18(5):798-804.
12.
Mahlangu JN, Andreeva TA, Macfarlane DE, Walsh C, Key NS. Recombinant B-
domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of 
bleeding in patients with congenital haemophilia A and inhibitors. Haemophilia. 
2017;23(1):33-41.
13.
Kruse-Jarres R, St Louis J, Greist A, et al. Efficacy and safety of OBI-1, an 
antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with 
acquired haemophilia A. Haemophilia. 2015;21(2):162-170.
14.
Brettler DB, Forsberg AD, Levine PH, et al. The use of porcine factor VIII 
concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor 
VIII. A multicenter US experience. Arch Intern Med. 1989;149(6):1381-1385.
15.
Hay CRM, Lozier JN, Lee CA, et al. Safety profile of porcine factor VIII and its 
use as hospital and home-therapy for patients with haemophilia-A and inhibitors: 
the results of an international survey. Thromb Haemost. 1996;75(1):25-29.
For non-commercial use only

BAX 802
Page 100 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16.
Baxter Healthcare Corporation. Package Insert: OBIZUR [antihemophilic factor 
(recombinant), porcine sequence] lyophilized powder for solution for intravenous 
injection.;2014. Web Link: 
https://www.baxter.com/assets/downloads/obizur_pI.pdf
17.
Lee CA. The evidence behind inhibitor treatment with porcine factor VIII. 
Pathophysiol Haemost Thromb. 2002;32 Suppl 1:5-8.
18.
Kasper C. Diagnosis and Management of Inhibitors to Factors VIII and IX - An 
Introductory Discussion for Physicians. Vol. 34. Diagnosis and Management of 
Inhibitors to Factors VIII and IX - An Introductory Discussion for Physicians: 
World Federation of Hemophilia (WFH); 2004:22. Web Link: 
http://www1.wfh.org/publications/files/pdf-1178.pdf
19.
Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents 
in cancer. In: MacLeod CM, ed. Evaluation of Chemotherapeutic Agents. New 
York: Columbia University Press; 1949:191-205.
20.
Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, 
Srivastava A. Definitions in hemophilia: Communication from the SSC of the 
ISTH. J Thromb Haemost. 2014;12(22):1935-1939.
For non-commercial use only

BAX 802
Page 101 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
22. SUMMARY OF CHANGES 
Protocol 241502: Amendment 4, 2017 JUN 28
Replaces: Global Amendment 1, 2016 FEB 03
In this section, changes from the previous version of the Protocol Amendment 1, dated 
2016 FEB 03, are described and their rationale is given.
1.
Throughout the document
Description of Change: Minor editorial changes to align with most current protocol 
template version, to update the list of abbreviations, administrative changes to the 
study team, and for improved clarity and consistency.
Purpose of Change: For consistency with the current Baxalta protocol template, and 
to improve clarity and consistency (note: minor edits and deletions that do not 
substantively change the protocol or are administrative in nature are not 
individually listed below). Note that changes that are found in the synopsis and 
more than one section in the body may have minor differences in wording; the 
common substantive changes are presented here.  
2.
Throughout the document
Description of Change: Changed analysis of endpoints from “Percentage of…” to 
“Proportion of…”. Changed “at least 10 surgeries in 10 evaluable male subjects” 
to “at least 12 procedures in 12 evaluable male subjects”
Purpose of Change: More suitable statistical and clinical terminology, revised 
expected enrollment.
3.
Throughout the document
Description of Change: Revised formula of loading dose of BAX 802 for major and 
minor surgeries as follows: 
Major surgery: [80 x body weight (U/kg)] + [body weight (kg) × 40
(1-[HCT[%]/100]) × anti-pFVIII inhibitor titer (BU)]
Minor surgery: [50 x body weight (U/kg)] + [body weight (kg) × 40
(1-[HCT[%]/100]) × anti-pFVIII inhibitor titer (BU)]
Purpose of Change: For greater clarity and accuracy.  
For non-commercial use only

BAX 802
Page 102 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
4.
Cover page
Description of Change: Updated administrative details to reflect new versions 
(local amendments 2 [Italy] and 3 [Russia] and global amendment 4) and NCT, 
EudraCT, and IND numbers.
Purpose of Change: Updated information.
5.
Section 1.1, Study Personnel, Investigator Acknowledgement Signature Page
Description of Change: Updated name of Sponsor representative.
Purpose of Change: Administrative change.
6.
Section 2, Section 12.1.1.2
Description of Change: Added text regarding the reporting of SUSARs.
Purpose of Change: For consistency with the current Baxalta protocol template.
7.
Synopsis
Description of Change: 
Added text to Active Product description: 
Dosage form: Injectable reconstituted solution of BAX 802, a recombinant form 
of porcine factor VIII (rpFVIII) from which the B domain has been deleted.
Dosage frequency: Loading dose, followed by PRN = as needed subsequent 
individualized dosing.
Mode of Administration: Intravenous bolus infusion (to the cubital vein is the 
recommended anatomical site of administration).
Purpose of Change: To align with body of protocol.
8.
Synopsis, throughout the document
Description of Change: Changed 12 10 surgeries procedures in 10 12 evaluable 
male subjects
Purpose of Change: To account for the addition of targeted enrollment of 
2 adolescent subjects.
9.
Synopsis, Section 7.3
Description of Change: Added Secondary Objective “3.
To determine the proportion of major surgeries with good or excellent hemostatic 
score” 
Purpose of Change: To align with endpoints.
For non-commercial use only

BAX 802
Page 103 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10. Synopsis, Section 7.3
Description of Change: Added text to Exploratory Objective 
 
 
 
Purpose of Change: Clarification; alignment with FDA request 
 
11. Synopsis, Section 7.4, Section 12.7.3
Description of Change: Added exploratory objective and endpoints for 
 
 
 
. 
Purpose of Change: To specify exploratory 
 
, and to match 
objectives and endpoints in the protocol.
12. Synopsis, Section 7.4
Description of Change: Added new exploratory objectives:
 
 
.
Purpose of Change: To specify exploratory objectives for the study.
13. Synopsis, Sections 7.3, 7.4
Description of Change: 
 
exploratory objectives:
 
 
. 
Purpose of Change: FDA request 
For non-commercial use only

BAX 802
Page 104 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
14. Synopsis, Section 8.2
Description of Change: Added text to Study Design as follows:
“This study is a Phase 3, prospective, open-label, uncontrolled, multicenter study to 
evaluate the efficacy and safety of BAX 802 in at least 12 10 surgeries procedures
in 10 12 evaluable male subjects with CHA with inhibitors to hFVIII who are 
undergoing major and or minor elective surgical, dental or other invasive 
procedures. The study will be conducted globally and will be divided into 
5 periods: Screening, Preoperative, Intraoperative, Postoperative, and End of 
study.”
Purpose of Change: Clarification and to align with protocol body; to reflect the new 
sample size for the study.
15. Synopsis, Section 8.1
Description of Change: Added “Subject Selection” section to synopsis, added new 
text as follows:
At least 5 of the procedures must be major surgeries in 5 evaluable subjects, of 
which no more than 20% can be dental or other non-operative invasive 
procedures. Elective surgical procedures will prospectively be defined as 
major or minor by the Investigator/surgeon, based on the protocol guidance 
and definitions and in consideration of each subject’s characteristics. 
Emergency surgeries are not in the scope of this study. Subjects may undergo 
more than 1 surgery or 2 parallel surgeries, such as bilateral knee 
replacement, however in these cases prior approval by the sponsor is required. 
In order to evaluate the activity of the product with respect to high-titer or 
high-responding inhibitors, at least 3 adult subjects with screening anti-hFVIII 
inhibitory antibody titers of ≥5 BU will be enrolled in the study.
Purpose of Change: Clarification and to align with protocol body.
16. Synopsis, Section 8.3
Description of Change: Updated study duration and expected completion date. 
Purpose of Change: Updated clinical trial conduct information.
17. Synopsis, Study Schedule, Throughout the document
Description of Change: Modified planned duration of subject participation to reflect 
revised End of Study Visit timing (42 ± 7 days after last dose). 
Purpose of Change: To align with changes to study schedule.
For non-commercial use only

BAX 802
Page 105 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
18. Throughout the document
Description of Change: Changed 3rd GHEA (GHEA3) score assessment from 
Day 14/discharge to discharge or within 24 to 72 hours after the last perioperative 
treatment dose of BAX802.
Purpose of Change: To provide a more meaningful post-operative GHEA 
assessment.
19. Synopsis, Section 8.4.1, Section 11.1
Description of Change: Added text “The primary outcome measure is the 
proportion of all surgical, dental, or other invasive procedures with a “good” 
or “excellent” response as measured by GHEA score, which is composed of 
3 individual ratings:” 
GHEA1: Assessment of intraoperative (Day 0) hemostatic efficacy of BAX 802 
performed by the operating surgeon at the end of surgery
GHEA2: Assessment of postoperative hemostatic efficacy of BAX 802 at 
postoperative Day 1 approximately (postoperative period) from end of surgery 
to and 24 ±6 hours after post-surgery performed by the operating surgeon. If a 
patient is discharged < 24 hours following surgery, then the 3rd GHEA 
hemostatic efficacy assessment may require a return visit the following day.
GHEA3: Assessment of overall perioperative hemostatic efficacy of BAX 802 at 
Day 14 or discharge related to the perioperative procedure or within 24 to 
72 hours after the last perioperative treatment dose of BAX 802 if 
hospitalization is prolonged for reasons other than perioperative procedures
(whichever is earlier), performed by the Investigator, and where possible, by the 
operating surgeon. Assessment by both is strongly recommended. In cases 
where there are differing assessments, the Investigator’s assessment will be 
used.  
The scores of each of the 3 individual ratings described above (GHEA1, GHEA2, 
GHEA3), will be added together to form a GHEA score. Hemostatic efficacy 
success is defined as an “excellent” or “good “outcome for ≥ 70% of 
hemostatic efficacy assessments.
Purpose of Change: Addition of pre-specified success criterion, revised assessment 
time, and specification of individuals making the assessment at request of FDA.
For non-commercial use only

BAX 802
Page 106 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. Synopsis, Section 8.4.1, Section 13.3
Description of Change: Added text to statistical analyses section to clarify that 
“For surgeries with up to two missing hemostatic assessments that did not 
necessitate rescue therapies, the rating of “fair” will be imputed for these 
missing data. These surgeries will be included in the FAS”.  
Purpose of Change: to clarify how outcomes will be measured and missing data 
will be addressed.
21. Synopsis, Section 8.4.2.1
Description of Change: modified first secondary outcome measure (expected intra-
and post-operative blood loss) to specify the comparative blood loss in healthy 
individuals “with similar demographic characteristics”. Added text to specify 
that Intraoperative is “from start of surgery until the end of surgery” and that 
Postoperative Day 1 is “from end of surgery” to approximately 24 hours ±6 hours
after surgery.  
Purpose of Change: To improve clarity for Investigators.
22. Synopsis, Section 8.4.2.1
Description of Change: added new secondary outcome measure:
“2.
Proportion of major surgeries with good or excellent hemostatic outcome 
together with its 2-sided 95% confidence interval”
Purpose of Change: Additional efficacy analysis requested by FDA.
23. Synopsis, Section 8.4.2.1
Description of Change: 
Exploratory 
Outcomes: “
.”
Purpose of Change: 
 as suggested 
by FDA.
24. Synopsis, Section 8.4.2, Section 11.1
Description of Change: Addition of new exploratory outcome measure: “
 
”.
Purpose of Change: The original secondary objective 
 
 
, and 
text modified for clarity.  
For non-commercial use only

BAX 802
Page 107 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
25. Synopsis, Section 8.4.2.2
Description of Change: added text specifying that IgG and IgM inhibitory and 
binding antibodies will be assessed during the study.
Purpose of Change: Clarification.
26. Synopsis, Section 8.4.3
Description of Change: Added Exploratory Outcomes:
Purpose of Change: 
 
27. Synopsis, Section 9.1
Description of Change: Revised Inclusion Criterion 2 to specify that only male 
subjects 12 to 75 years of age and under will be enrolled, Added text to Inclusion 
Criterion 8 specifying that “Subject is hepatitis C virus negative (HCV-) by 
antibody or polymerase chain reaction (PCR) testing; or HCV+ with chronic stable 
hepatitis disease. If positive, the antibody titer will be confirmed by PCR.”   
Purpose of Change: For consistency within the protocol regarding ineligibility of 
female patients. To address those potential patients who may have been on 
long-term treatment with bypassing agents and whose levels of inhibitors would 
therefore be lower, but who should still be considered eligible for the study as they 
are patients with inhibitors who can no longer be treated with human FVIII. To 
include subjects with high-titer or high-responding inhibitors and to increase 
maximum age of study subjects at request of FDA; edits for clarification and 
consistency.
28. Synopsis, Section 9.1
Description of Change: Revised Inclusion Criterion 3 to allow for assent of 
adolescent subjects: “Subject has provided signed informed consent (and assent 
for adolescent subjects, as applicable) in accordance with local regulatory 
requirements”
Purpose of Change: To allow for enrollment of adolescent subjects.
For non-commercial use only

BAX 802
Page 108 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
29. Synopsis, Section 9.2
Description of Change: Removed weight exclusion criterion. Added new Exclusion 
Criterion 9 Subject has an ongoing or recent (within previous 3 months) 
thrombo-embolic disease, fibrinolysis or disseminated intravascular 
coagulation (DIC).
Purpose of Change: Weight restriction removed at request of FDA. New exclusion 
criterion added to reflect current safety profile of IP. Other minor edits to exclusion 
criteria as appropriate for clarity and consistency.
30. Synopsis, Section 13.1
Description of Change: Revised text to reflect enrollment of adolescent subjects.
Sample Size and Power Calculations
The total sample size of surgeries for the study is 12 evaluable subjects, which 
includes at least 10 12 procedures in 12 10 evaluable male subjects (at least 
5 major surgeries in 5 evaluable subjects) and at least 2 adolescents (≥12 to 
< 18 years old). The sample size, as defined in the protocol, was chosen to provide 
sufficient evidence of safety and effectiveness for this indication and is not based 
on statistical considerations. 
Evaluable subjects are defined as subjects who met all study entry criteria and who 
had at least one all the 3 hemostatic efficacy assessments as per Section 8.4.1.
Purpose of Change: To align with changes to other parts of the protocol regarding 
sample size. To better define evaluable subjects.
31. Synopsis, Section 13.4.1, Tables 8, 9, and 10
Description of Change: Changed 3rd GHEA assessment from Day 14 to discharge 
or within 24 to 72 hours after last perioperative dose (whichever is earlier) and 
would be assessed by both surgeon and PI and added the following text:
…
The primary efficacy measure will be the overall assessment of hemostatic efficacy 
assessed intraoperatively and postoperatively by the surgeon at postoperative Day 1 
(ie, the day following the day postoperative period, i.e., from end of surgery up to 
24to between 12 and 24 hours post-surgery) and perioperatively at postoperative 
Day 14 visit 24 to 72 hours after the last perioperative treatment dose of 
BAX 802 is administered or discharge (whichever is earlier) by the surgeon and 
by the Investigator (hemophilia physician), and where possible, by both the 
Investigator and the operating surgeon (assessment by both is strongly 
recommended), and, and will be summarized the sum of intraoperative, 
postoperative, and perioperative by the GHEA scores as and rated “excellent”, 
“good”, “fair” and or “none”. If discharge is delayed for a reason other than 
For non-commercial use only

BAX 802
Page 109 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
surgery related bleeding (e.g., pneumonia), an assessment at 24 to 72 hours 
after last perioperative treatment dose of BAX 802 will ensure that the overall 
perioperative assessment is completed close to the last administered study 
drug dose. Wherever possible (except for intraoperative assessment), bleeding 
should be assessed by both operating surgeon and Investigator. To achieve the 
hemostatic efficacy success will be defined as a rating of criteria, the study needs 
to achieve a ≥70% rate of hemostatic efficacy assessments with an “excellent 
and/” or “good.” outcome in at least 12 procedures.    
…
OwingDue to the possibility of a subject undergoing multiple surgeries per 
subject, the statistical entity on whichanalysis of the primary outcome measure 
will be reported ison the by-surgery level (i.e., not by the number of subjects). In 
cases where two or more surgical procedures are performed in the same 
intraoperative settings (under the same anesthesia e.g., bilateral knee 
replacement) the surgery will be counted as one surgery. Blood loss assessment 
from those surgeries will be assessed as one. In the event that the subject is 
planning to have additional surgery in the future, they will need to complete 
the study and be re-screened again to ensure that they continue to meet the 
eligibility criteria.
…
Point estimates and corresponding 2-sided exact Clopper-Pearson confidence 
intervals (CIs) at the 90 95% confidence level will be calculated for the rate of 
hemostatic efficacy assessments with excellent/good outcome for descriptive 
purposes.
…
The proportion of major surgeries with hemostatic success will be reported 
along with exact 95% CIs. A treatment success will be defined as a rating of 
excellent or good. 
…
A sensitivity analysis based on the first surgery will be performed if more than 
20% of subjects have multiple surgeries.
Purpose of Change: Changed 2-sided CIs from 90% to 95%, added prospective 
sensitivity analysis in case > 20% of subjects have multiple surgeries, added new 
secondary outcome measure “Proportion of major surgeries with good or excellent 
hemostatic score” to align with changes to study assessments and addition of 
sensitivity analysis per FDA request.
For non-commercial use only

BAX 802
Page 110 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
32. Section 6.2
Description of Change: Revised text as follows: “Overall, CHA accounts for about 
80% of hemophiliacs. It affects all ethnic populations and its prevalence varies 
among different countries, but is estimated at a rate of 3 to 20 cases per 100,000 
population. The World Federation of Hemophilia (WFH) has estimated the total 
number of hemophilia cases at about 500,000 universallyworldwide, of which one-
third are diagnosed. The tendency to bleed in these subjects correlates with the 
plasma level of FVIII. This lifelong disorder has 3 clinical phenotypes (severe, 
moderate, and mild) that correlate with FVIII levels in plasma (< 1%, 1 to 5%, and 
5 to 3040%, respectively)”
Purpose of Change: Reworded for clarity; correction.
33. Section 6.3; Section 8.1 
Description of Change: Added text specifying that of the at least 5 major surgeries 
in 5 evaluable subjects in the study, no more than 20% could be dental or other 
non-operative invasive procedures. Added text “In order to evaluate the activity 
of the product with respect to high-titer or high-responding inhibitors, at least 
3 adult subjects with screening anti-hFVIII titers of ≥5 BU will be enrolled in 
the study”. 
Purpose of Change: To ensure that the surgical procedures captured in this study 
are representative of the full spectrum of possible surgeries and to include subjects 
with high-titer or high-responding inhibitors at request of FDA.
34. Section 6.4.2 
Description of Change: Added enrollment numbers for previous clinical trials. 
Revised text as follows: 
“At the time of OBIZUR® marketing approval, the clinical trial data indicated that 
rpFVIII was well tolerated and had demonstrated effectiveness in the control of 
bleeding in study subjects. Cumulatively (patient exposure from 01 Oct 2014 
through 30 Apr 2016), approximately 16,424,000 units (U) of OBIZUR® were 
sold worldwide. Median (range) treatment dose per bleeding episode was 
94,500 (35,256 to 182,700), and the estimated number of patient-years
worldwide to OBIZUR® was approximately 357.6 (179.8 to 931.6) (PBRER 
[DLP 31Oct2016]). As of 2015 December 3111 Nov 2017, there have been 420
post-marketing spontaneousserious case reports with 36 adverse event 
reports.AEs. No adverse reactions other than those observed in clinical trials 
have been observed in the post marketing setting. The reports were considered 
possibly associated and consistent with the known safety profile of OBIZUR®.14”
For non-commercial use only

BAX 802
Page 111 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Purpose of Change: Clarification, and to reflect updated safety information for 
study drug.
35. Section 8.2
Description of Change: Added text specifying geographic scope of study.
Purpose of Change: Requested by FDA.
36. Section 8.2.1.1, Section 8.2.1.2 
Description of Change: Added text specifying that extraction of fewer than 3 teeth 
(or third molar) would be considered minor surgery.
Purpose of Change: To improve clarity.
37. Section 8.2.2 
Description of Change: Deletion of the following text: “This regimen for loading 
dose of BAX 802 proposed for Study BAX 802 Surgery takes into account the titer 
of anti-pFVIII inhibitors”.
Purpose of Change: Editorial change.
38. Section 8.4.1 
Description of Change: Added text specifying that surgeries with one or two 
missing hemostatic assessments that did not necessitate rescue therapies will have 
the rating of “fair” imputed for these missing data. These surgeries will be included 
in the FAS.
Purpose of Change: To improve clarity.
39. Section 8.4.1 
Description of Change: Added text as follows: “Prior to the surgery, the 
surgeon/Investigator will predict the estimated volume (in mL) of the expected 
blood loss for the planned surgical intervention in a hemostatically normal 
individual of the same sex, age, and stature as the study subject, for 
intraoperative, postoperative, and overall perioperative time periods. Every 
effort should be made to predict the volume as precisely as possible, also 
taking into account, for example, the use of a tourniquet or placement of a 
postoperative drain and whether or not suction is used. The estimate will be 
for the intraoperative time period and from completion of the procedure until 
approximately 24 hours post-surgery and for the overall perioperative period
(see Section 11.2.1).”
Purpose of Change: To clarify the recording of predicted blood loss.
For non-commercial use only

BAX 802
Page 112 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
40. Section 8.4.1, Tables 2 through 4
Description of Change: Added text specifying that rescue therapy includes use of 
other FVIII products.
Purpose of Change: To improve clarity.
41. Section 8.4.1, Tables 2, 3 and 4
Description of Change: In all 3 tables, added text specifying GHEA assessment 
number.
Table 2 – changed 1st row as follows: At the end of surgerytime of discharge from 
the OR, the operating surgeon will assess the intraoperative hemostatic efficacy
Table 3 – changed 1st row as follows: On postoperative Day 1 (24 ± 6 hours 
post-surgery), the operating surgeon will assess the postoperative hemostatic 
efficacy by the operating surgeon
Table 4 – changed 1st row as follows: At Day 14 or discharge or within 24 to 
72 hours after the last perioperative treatment dose of BAX 802 (whichever is 
earlier), a hematologist will assess the postoperative efficacy assessment will be
performed by the Investigator, and where possible, and where possible, by 
both the Investigator and the operating surgeon
Purpose of Change: To align with changes elsewhere in the protocol regarding 
timing of GHEA assessments.
42. Section 8.6, Section 15.4
Description of Change: Replaced internal Safety Monitoring Committee with 
external data safety monitoring board (DSMB).
Purpose of Change: Requested by FDA.
43. Section 8.7
Description of Change: Added detailed description of IP as follows:
“The IP, BAX 802, is a recombinant purified form of porcine factor VIII 
(rpFVIII) from which the B domain has been deleted and replaced with a 24 
amino acid linker. Recombinant pFVIII (BAX802) is expressed as a 
glycoprotein by a genetically engineered BHK cell line. The molecular weight 
of rpFVIII is approximately 175 kDa (based on its 1448 amino acid sequence) 
and has 86% pair-wise sequence homology with hFVIII.”
Purpose of Change: To improve comprehensiveness of IP description.
For non-commercial use only

BAX 802
Page 113 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
44. Section 8.7.1
Description of Change: Added text describing IP storage instructions as follows:
“BAX 802 should be kept refrigerated at 2°C to 8°C (36°F to 46°F). The 
following precautions should be taken:
--Do not freeze
--Do not use if frozen, even if it has been thawed
--Do not use beyond the expiration date printed on the carton or vial
--Do not use after > 3 hours of reconstitution.” 
Purpose of Change: Added to clarify storage instructions for sites.   
45. Section 8.7.2
Description of Change: Added text describing anatomical location of infusion:
“The reconstitution procedures for BAX 802 are detailed in the Pharmacy Manual. 
Reconstituted BAX 802 should be kept and administered at room temperature and 
must be administered within 3 hours of reconstitution.
BAX 802 will be administered as an intravenous bolus infusion to the cubital vein
per the dosing schema for major and minor surgeries (Table 5).” 
Purpose of Change: Added to clarify IP administration instructions for sites.   
46. Section 8.7.3.3.1
Description of Change: Added text clarifying that the loading dose of BAX 802 
should be (administered approximately 1 to 2 hours prior to the surgery)
Purpose of Change: Added to clarify IP dosing instructions for sites.   
47. Section 8.7.3.3.2
Description of Change: Added text clarifying dosing procedures for BAX 802 as 
follows:
In case of major surgery, The recommended FVIII target level is ≥80% for major 
surgeries/procedures and ≥50% for minor surgeries/procedures.
It is recommended that the surgery starts after FVIII levels have achieved target 
levels. If However, if FVIII activity post loading dose is close to the target level, a 
supplemental dose of BAX 802 should be administered without further delaying 
the surgery, based on Investigator's judgement. Close to the target for major 
and minor surgeries will be defined as levels of ≥70% for major and ≥40% 
for minor surgery respectively. This is 10% from the target, which is 
considered a normal variation.  
If FVIII activity post loading dose is not close to the target level, a supplement 
dose of BAX 802 should be administered and surgery delayed until FVIII 
levels have achieved target levels or are in close range.
For non-commercial use only

BAX 802
Page 114 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Subjects will receive subsequent doses of BAX 802 in order to achieve the 
FVIII target level (See Table 5). All subsequent dosing of BAX 802 should be 
preceded by measurement of residual FVIII levels and dose adjustments must be 
based on the most recent residual FVIII activity levels.
Purpose of Change: Added to clarify IP dosing instructions for sites.   
48. Section 8.7.3.3.3, Section 8.7.3.3.4
Description of Change: Revised section by reordering text, adding diagram, 
removing text instructions for monitoring of FVIII and postoperative dosing, and 
adding text addressing the timing of discontinuation of postsurgery IP due to 
operational issues at site.
Added:
All surgeries/procedures are to have FVIII levels monitored per the diagram in 
Figure 1:
Figure 1: Postoperative FVIII Monitoring
More frequent monitoring of FVIII activity is advised in subjects who have baseline anti-
pFVIII inhibitor titers of > 0.6 BU.
All subsequent dosing of BAX 802 must be preceded by measurement of residual FVIII levels 
pre-dose and FVIII level measurement 30 ±5 minutes post-dosing. 
…
FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as 
necessary.
FVIII activity level should also be determined within 4 to 6 hours 
following major or minor surgery, with dose adjustments as 
necessary.
FVIII activity level should be determined at least every 12 hours 
until 48 hours postoperative period (if not discharged yet), with 
dose adjustments as necessary.
Major Surgeries: Beginning on 
postoperative Day 3 (through 
discharge), subjects will have FVIII 
level measurement at least once per 
day in order to assess the adequacy 
of BAX 802 therapy during the 
postoperative period. For 
consistency, it is recommended that 
the daily blood draws are performed 
at the same time of the day, such as 
morning blood draws.
Minor Surgeries: In case the subject 
is hospitalized for more than 24 
hours, daily pre- and post-infusion 
FVIII level determinations as 
described for major surgery have to 
be performed and the dose adjusted 
according to the residual FVIII levels.
For non-commercial use only

BAX 802
Page 115 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The following text was deleted in two places:
Note:
FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as necessary. 
FVIII activity level should also be determined within 4 to 6 hours following 
major surgery, with dose adjustments as necessary. 
Following this, FVIII activity level should be determined at least every 12 hours 
till 48 hours postoperative period (if not discharged yet), with dose adjustments 
as necessary.
Beginning on postoperative Day 3 (through discharge), subjects will have FVIII 
level measurement at least once per day in order to assess the adequacy of 
BAX 802 therapy during the postoperative period. For consistency, it is 
recommended that the daily blood draws are performed at the same time of the 
day, such as morning blood draws.
More frequent monitoring of FVIII activity is advised in subjects who have 
baseline anti-pFVIII inhibitor titers of >5 BU.
ALL subsequent dosing of BAX 802 must be preceded by measurement of residual 
FVIII levels pre-dose and FVIII level measurement 30 ±5 minutes post-dosing.
New text added: “If a subject is discharged or cannot be continued on IP at the 
study site, (e.g., because the clinic is closed on weekends), study participation 
should end at the time of hospital discharge and follow-up treatment, if any, 
should proceed with SOC products as per Investigator’s discretion.
Note: IP (BAX 802) will not be dispensed to the subjects for in-home use.”
Purpose of Change: Added to improve readability of section, and to address 
postsurgical use of BAX 802.
49. Section 9.3
Description of Change: Deleted noncompliance as reason for withdrawal text.
Purpose of Change: Not applicable in this study where IP is administered in a 
surgical setting.
50. Section 10.2
Description of Change: Changed site numbers from 2 to 3 digits.
Purpose of Change: To align with current Baxalta standards.
For non-commercial use only

BAX 802
Page 116 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
51. Section 10.4.1
Description of Change: Modified text to reflect revised End of Study Visit timing 
(42 ± 7 days after last dose): 
Discharge Visit will be performed when the subject is discharged and the. The End 
of Study Visit will be performed 42 to 49± 7 days following the completion of the 
surgical procedure. In cases where the Discharge Visit would occur within 3 days 
of either the Day 14 or the End of Study Visit, the respective visits willcan be done 
as a single visit. Sites must make every effort to complete 3 independent GHEA 
assessments for both minor and major procedures, preferably allowing for as 
much time as possible to pass between assessments within the windows 
specified in this protocol.
Purpose of Change: To align with changes to study schedule.
52. Section 10.4.2
Description of Change: Modified text to reflect revised Antibody Testing Visit. 
“10.4.2
Optional Antibody Testing Visit
Whenever feasible, aA visit will be performed between 7 to 14 days after the 
subject is discharged.last perioperative dose of BAX 802. Study procedures will 
be performed as per Table 9 and blood samples will be collected for antibody 
testings and other tests as per Table 10. This visit is optional.
Purpose of Change: To reflect that the 7 to 14 day antibody assessment is to be 
required for all subjects.
53. Section 10.4.3
Description of Change: Added new section for “Unscheduled Visits”.
Purpose of Change: To align with changes elsewhere in the amended protocol.  
54. Section 10.5
Description of Change: Added text to clarify that certain prohibited concomitant 
medications may be used as rescue drugs: 
The following medications are not permitted before discharge (unless used as 
rescue medications or used to treat unrelated/surgical site bleeding episodes as 
specified below):
…
For non-commercial use only

BAX 802
Page 117 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Hemophilia inhibitor bypassing therapy (recombinant factor VIIa [NovoSeven] 
within 3 hours or activated prothrombin complex concentrate [aPCC (FEIBA)] 
within 6 12 hours prior to initial BAX 802 administration) unless used as a rescue 
medication (Section 10.5) after failure/study withdrawal or used to treat 
unrelated/surgical site bleeding episodes (Section 11.2.3)
Purpose of Change: To clarify rescue medication use.
55. Section 11.2.1
Description of Change: Added text to clarify recording of expected blood loss prior 
to surgery:
The observed versus predicted (recorded prior to surgery) operative blood loss 
will be described for the period from initiation of the intervention to discharge or 
14 days 24 to 72 hours after the intervention last perioperative treatment dose of 
BAX 802 (whichever is first), as applicable
….
“The expected normal/average, and maximal blood loss and transfusion 
requirement estimate will be timestamped into the source documentation 
and/or blood loss form prior to surgery into the CRF. No changes will be 
allowed to these estimates after the surgery.”
Purpose of Change: Per FDA request.
56. Section 11.2.3
Description of Change: Added text to clarify bleeding episodes as follows: 
Bleeding episodes will be classified as follows:
Unrelated bleeding episodes: an unrelated bleeding episode is defined as any 
bleeding occurring at a different anatomical site than the surgery site during 
the postoperative period. Treatment of such events should be performed as per 
Section 11.2.5 and Table 6.
Surgical site bleeding episodes: Surgical site bleeding episodes are any 
bleeding at the surgical/procedure site which occurs after discharge (related to 
the perioperative procedure) or 72 hours after the last perioperative treatment 
dose of BAX 802 (if hospitalization is prolonged for reasons other than 
perioperative procedures), whichever is earlier.
These bleeding episodes will be treated as follows:
For non-commercial use only

BAX 802
Page 118 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If these unrelated bleeding episodes or surgical site bleeding episodes occur 
during the subject's stay in hospital, it is recommended that subjects are 
treated with BAX 802. BAX 802 will be dosed as per the most recent residual 
FVIII activity level and clinical judgment using the dosing regimen provided 
in Table 6 [Required dose = body weight (kg) × desired FVIII rise (U/dL or % 
of normal)]/1.2 (U/kg per U/dL)]. All subsequent dosing of BAX 802 should be 
preceded by measurement of residual FVIII levels and dose adjustments must 
be based on the most recent residual FVIII activity levels.
If these unrelated bleeding episodes or surgical site bleeding episodes occur 
after the subject has been discharged, subjects may be treated with BAX 802 
or SOC, as per Investigator's discretion.
An unscheduled visit could be performed for management of bleeding 
episodes.
Note: IP (BAX 802) will not be dispensed to the subjects for in-home use.
Purpose of Change: To clarify bleeding episodes.
57. Section 11.2.5
Description of Change: Added text regarding bleeding episodes at the surgical site 
and to clarify possible use of IP to treat unrelated bleeding episodes as follows: 
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical Site 
Bleeding Episodes
An unrelated bleeding episode is defined as any bleeding occurring at a 
different anatomical site than the surgery site during the postoperative period. 
Surgical site bleeding episodes are any bleeding at the surgical/procedure site 
which occurs after discharge (related to the perioperative procedure) or 72 
hours after the last perioperative treatment dose of BAX 802 (if hospitalization 
is prolonged for reasons other than perioperative procedures), whichever is 
earlier. These bleeding episodes will be treated as per Section 11.2.3.
If subject is treated with BAX 802 for unrelated bleeding episodes or surgical site 
bleeding episodes, the subject will rate the severity (minor, moderate, or major) of 
the bleeding episode and will rate the overall treatment response at 24 ±2 hours 
after the initiation of treatment and at the resolution of bleed (if not resolved within 
24 hours) using a 4-point efficacy rating scale (Table 7). Data could be collected 
as an unscheduled visit.”
For non-commercial use only

BAX 802
Page 119 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
…
Table 7: Efficacy Rating Scale for Treatment of Unrelated/Surgical Site Bleeding 
Episodes 
Purpose of Change: To clarify that BAX 802 may be used to treat unrelated 
bleeding episodes at the study site per the Investigators' judgment.
58. Section 12.1.1.1.1
Description of Change: Added text to SAE section, added new section for 
Inhibitory Serious Adverse Events:
The confirmed development of de-novo anti-pFVIII inhibitory antibodies or 
increases of >10 BU in pre-existing titers of anti-pFVIII inhibitory antibodies 
(See Section 12.1.1.1.1)
Section 12.1.1.1.1
Inhibitory Serious Adverse Events
The development of de-novo anti-pFVIII inhibitory antibodies (≥0.6 BU) must 
be confirmed with a second blood draw 7 to 14 days after the initial confirmed 
positive de novo result (or repeat testing of original sample if a second draw is 
not possible). Confirmation of de novo inhibitory antibodies or a confirmed 
increase of > 10 BU in pre-existing titers of anti-pFVIII inhibitory antibodies
must be reported as a SAE within 24 hours, and followed up. 
Increases in pre-existing titers of anti-pFVIII inhibitory antibodies will 
require a second confirmatory test 7 to 14 days after the initial confirmed 
positive increase (or repeat testing of original sample if a second draw is not 
possible). If the protocol-defined significant increase (> 10 BU) is confirmed it 
will be reported as an SAE.
Safety will be further monitored by the Investigator and medical monitor to 
evaluate the clinical significance of the inhibitor level. Although the 
development of, or increase in, anti-rpFVIII inhibitory antibody titers may not 
necessarily indicate a failure of response to BAX 802, the inhibitor levels and 
patient response will be closely monitored and an alternative therapy will be 
considered for lack of efficacy, if applicable.
Purpose of Change: Per FDA request.
For non-commercial use only

BAX 802
Page 120 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
59. Section 12.1.1.2
Description of Change: Added new section for SUSARs:
12.1.1.2
Suspected Unexpected Serious Adverse Reaction 
Any suspected adverse reaction to study treatment that is both serious and 
unexpected. 
The event(s) must meet all of the following:
     --Suspected adverse reaction
     --Serious
     --Unexpected
     --Assessed as related to study treatment
Once determined to meet the criteria for a SUSAR, an SAE should be 
submitted to regulatory agencies expeditiously.
Purpose of Change: To align with the current Baxalta protocol template.
60. Section 12.1.2.3
Description of Change: Deleted references to EDC and eCRFs.
Purpose of Change: This study will use paper CRFs.
61. Section 12.7.3
Description of Change: Revised text as follows:
A central reference laboratory will perform assays (anti-pFVIII, anti-hFVIII, and 
anti BHK) on samples taken at Screening, Day 14 or discharge (whichever is 
earlier), and End of Study Visits.the time indicated in Table 9 and Table 10.
Binding antibodies to pFVIII, hFVIII, and BHK, will be measured using ELISA. 
Binding antibodies to human and porcine FVIII (both IgG and IgM) and 
binding antibodies to BHK proteins will be analyzed using validated ELISAs 
using a multi-tiered approach consisting of screening assay, titer 
determination and confirmation of specificity. 
 
 
 
Purpose of Change: To clarify immunogenicity assessments.
For non-commercial use only

BAX 802
Page 121 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
62. Section 12.8
Description of Change: Added text specifying that vital signs will be collected at 
unscheduled visits.  
Purpose of Change: To improve clarity and consistency.
63. Section 12.10
Description of Change: Added text specifying that samples will be collected for 
anti-pFVIII, anti hFVIII, and anti-BHK binding antibodies, and added reference to 
new Inhibitory SAE Section 12.1.1.1.1.
Purpose of Change: To improve clarity and to align with changes to other parts of 
the protocol.
64. 13.4.3 Exploratory Outcome Measures (new section)
Description of Change: Added text to address exploratory outcome measure 
analyses.
 
.
 
 
.
 
 
 
 
 
 
.
 
.
Further details will be included in the SAP.
Purpose of Change: To align with changes to other parts of the protocol regarding 
exploratory analyses.
For non-commercial use only

BAX 802
Page 122 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
65. Section 13.5
Description of Change: Removed interim analysis text.
Purpose of Change: No interim analyses are planned for this study.
66. Section 20, Table 8
Description of Change: Revised to reflect changes in study procedures as described 
in the protocol body.  
Purpose of Change: Consistency with other changes.   
67. Section 20, Table 9
Description of Change: Revised table reflect changes in study procedures as 
described in the protocol body.  
Purpose of Change: Consistency with other changes.
68. Section 20, Table 10
Description of Change: Revised table reflect changes in study procedures as 
described in the protocol body.  
Purpose of Change: Consistency with other changes.
69. Section 21
Description of Change: Deleted reference #14.  
Purpose of Change: New Obizur safety report will be referenced as a footnote and 
not an end of text reference.
For non-commercial use only

BAX 802
Page 123 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX 802) in Subjects with Congenital Hemophilia A with Factor VIII Inhibitors 
Undergoing Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 4: 2017 JUN 28
Replaces: GLOBAL AMENDMENT 1: 2016 FEB 03
OTHER ID(s)
NCT Number: NCT02895945
EudraCT Number: 2015-005521-39
IND NUMBER: BB-IND 014798
By signing below, the Investigator acknowledges that he/she has read and understands 
this protocol, and will comply with the requirements for obtaining informed consent from 
all study subjects prior to initiating any protocol-specific procedures, obtaining written 
initial and ongoing EC(s) protocol review and approval, understands and abides by the 
requirements for maintenance of source documentation, and provides assurance that this 
study will be conducted according to all requirements as defined in this protocol, Clinical 
Trial Agreement, ICH GCP guidelines, and all applicable national and local regulatory 
requirements.
Signature of Principal Investigator
Date
Print Name of Principal Investigator
For non-commercial use only

BAX 802
Page 124 of 124
Clinical Study Protocol Identifier: 241502
2017 JUN 28
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX 802) in Subjects with Congenital Hemophilia A with Factor VIII Inhibitors 
Undergoing Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 4: 2017 JUN 28
Replaces: GLOBAL AMENDMENT 1: 2016 FEB 03
OTHER ID(s)
NCT Number: NCT02895945
EudraCT Number: 2015-005521-39
IND NUMBER: BB-IND 014798
By signing below, the Investigator acknowledges that he/she has read and understands 
this protocol, and provides assurance that this study will be conducted according to all 
requirements as defined in this protocol, Clinical Trial Agreement, ICH GCP guidelines, 
and all applicable national and local regulatory requirements.
Signature of Coordinating Investigator
Date
Print Name and Title of Coordinating Investigator
Signature of Sponsor Representative
Date
, MD
, Clinical Programs and Therapeutic Area Head
Baxalta Innovations GmbH
For non-commercial use only

BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
CLINICAL STUDY PROTOCOL
PRODUCT: BAX 802
STUDY TITLE:
A Phase 3, Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of 
B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects with 
Congenital Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or Other 
Invasive Procedures
STUDY SHORT TITLE: BAX 802 in Congenital Hemophilia A with Inhibitors
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 6: 2017 DEC 14
Replaces:
AMENDMENT 4: 2017 JUN 28
ALL VERSIONS: 
Amendment 6: 2017 DEC 14
Amendment 5 (Russia): 2017 AUG 08
Amendment 4: 2017 JUN 28
Amendment 3 (Russia): 2017 FEB 07
Amendment 2 (Italy): 2016 AUG 22
Amendment 1: 2016 FEB 03
Original: 2015 SEP 30
OTHER ID(s)
NCT Number:
NCT02895945
EudraCT Number:
2015-005521-39
IND NUMBER: 
BB-IND 014798
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362, 
UNITED STATES
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna, 
AUSTRIA
For non-commercial use only

BAX 802
Page 2 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
, Clinical Programs and Therapeutic Area Head
Baxalta Innovations GmbH
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with 
the study (e.g., Investigator(s), sponsor’s medical expert and study monitor, sponsor’s 
representative(s), laboratories, steering committees, and oversight committees (including 
ethics committees [ECs], as applicable) will be maintained by the sponsor and provided 
to the Investigator.
For non-commercial use only

BAX 802
Page 3 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
2. SERIOUS ADVERSE EVENT REPORTING
The Investigator will comply with applicable laws/requirements for reporting serious 
adverse events (SAEs) to the ECs.
ALL SAEs, INCLUDING SUSPECTED UNEXPECTED SERIOUS ADVERSE 
REACTIONS (SUSARs), MUST BE REPORTED ON THE SERIOUS ADVERSE 
EVENT REPORT (SAER) FORM AND TRANSMITTED TO THE SPONSOR 
WITHIN 24 HOURS AFTER BECOMING AWARE OF THE EVENT.  SAEs 
MUST ALSO BE RECORDED ON THE ADVERSE EVENT CASE REPORT 
FORM (CRF).
Drug Safety contact information: see SAER form
Refer to SAE Protocol Sections and the study team roster for further information.
For definitions and information on the assessment of these events, refer to the following:

AEs, Section 12.1

SAE, Section 12.1.1.1

SUSARs, Section 12.1.1.2

Assessment of AEs, Section 12.1.2
For non-commercial use only

BAX 802
Page 4 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
3. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of Investigational Product (IP)
BAX 802
Name(s) of Active Ingredient(s)
Recombinant Porcine Factor VIII (rpFVIII)
CLINICAL CONDITION(S)/INDICATION(S)
Congenital hemophilia A (CHA) patients with inhibitors to Factor VIII (FVIII) undergoing surgical and 
other invasive procedures
PROTOCOL ID
241502
PROTOCOL TITLE
A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine 
Factor VIII (BAX 802) in Subjects with Congenital
Hemophilia A with Factor VIII Inhibitors Undergoing Surgical or 
Other Invasive Procedures
Short Title
BAX 802 in CHA with Inhibitors 
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2016, DEC
Primary Completion
2019, MAR
Study Completion
2019 MAR
Duration
Approximately 28 months
STUDY OBJECTIVES AND PURPOSE
Study Purpose
To evaluate the efficacy and safety of BAX 802 in males with CHA with inhibitors who are undergoing 
major or minor elective surgical, dental, or other invasive procedures.
Primary Objective
To evaluate the perioperative hemostatic efficacy of BAX 802 in male subjects with CHA with inhibitors 
to human factor VIII (hFVIII) undergoing major or minor elective surgical, dental, or other invasive 
procedures as determined by the Global Hemostatic Efficacy Assessment (GHEA) score.
Secondary Objectives
1.
To determine the safety of BAX 802 used in the perioperative setting by assessing:

The development of and change in titer of anti-porcine FVIII (pFVIII) and anti-hFVIII antibodies 
(binding and neutralizing), and development of binding antibodies to baby hamster kidney (BHK) 
proteins

The occurrence of thrombo-embolic events and/or allergic reactions to BAX 802

The occurrence of adverse events (AEs) related to BAX 802
For non-commercial use only

BAX 802
Page 5 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

The occurrence of clinically significant changes in vital signs and routine laboratory parameters 
related to BAX 802
2.
To determine the intraoperative, postoperative, and overall perioperative blood loss, compared to the 
estimated volume of expected average and maximum blood loss in a comparable healthy individual as 
predicted preoperatively by the Investigator/surgeon
3.
To determine the proportion of major surgeries with good or excellent hemostatic score
4.
To determine the daily and total weight-adjusted administration of BAX 802 per subject
Exploratory objectives 
 
 
 
 
STUDY DESIGN
Study Type/ Classification/ 
Discipline
Efficacy and Safety
Control Type
No control arm
Study Indication Type
Treatment
Intervention model
Single-group
Blinding/Masking
Open-label
Study Design
This study is a Phase 3, prospective, single-arm, open-label, uncontrolled, 
multicenter study to evaluate the efficacy and safety of BAX 802 in at 
least 12 procedures in 12 evaluable male subjects with CHA with 
inhibitors to hFVIII who are undergoing major or minor elective surgical, 
dental or other invasive procedures. The study will be conducted globally 
and will be divided into 5 periods: Screening, Preoperative, Intraoperative, 
Postoperative, and End of study.
Subject Selection
At least 5 of the procedures must be major surgeries in 5 evaluable 
subjects, of which no more than 20% can be dental or other non-operative 
invasive procedures. Elective surgical procedures will prospectively be 
defined as major or minor by the Investigator/surgeon, based on the 
protocol guidance and definitions and in consideration of each subject’s 
characteristics. Emergency surgeries are not in the scope of this study. 
For non-commercial use only

BAX 802
Page 6 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Subjects may undergo more than 1 surgery or 2 parallel surgeries, such as 
bilateral knee replacement, however in these cases prior approval by the 
sponsor is required. In order to evaluate the activity of the product with 
respect to high-titer or high-responding inhibitors, at least 3 adult subjects 
with screening anti-hFVIII inhibitory antibody titers of ≥5 Bethesda units 
(BU) will be enrolled in the study.
Planned Duration of 
Subject Participation
The duration of subject participation depends on the nature of the invasive 
procedure: it will run from the signing of the informed consent until 
completion of the End of Study Visit (42 ± 7 days after last perioperative 
dose of BAX 802).
Primary Outcome Measure 
The primary outcome measure is the proportion of all surgical, dental, or other invasive procedures with a 
“good” or “excellent” response as measured by GHEA score, which is composed of 3 individual ratings:

GHEA1: Assessment of intraoperative (Day 0) hemostatic efficacy of BAX 802 performed by the 
operating surgeon at the end of surgery.

GHEA2: Assessment of postoperative hemostatic efficacy of BAX 802 at postoperative Day 1 
(approximately 24 hours [±6 hours] post-surgery) performed by the operating surgeon. (Note: If a 
patient is discharged < 24 hours following surgery, then the GHEA2 hemostatic efficacy assessment 
will require a return visit the following day.)

GHEA3: Assessment of overall perioperative hemostatic efficacy of BAX 802 at the GHEA3 Visit 
(discharge or within 24 to 72 hours after the last perioperative treatment dose of BAX 802 if 
hospitalization is prolonged for reasons other than perioperative procedures [whichever is earlier]), 
performed by the Investigator, and where possible, also by the operating surgeon. Assessment by 
both is strongly recommended. In cases where there are differing assessments, the Investigator’s 
assessment will be used. 
The scores of each of the 3 individual ratings described above (GHEA1, GHEA2, and GHEA3), will be 
added together to form a GHEA score. Hemostatic efficacy success is defined as an “excellent” or “good 
“outcome for ≥ 70% of hemostatic efficacy assessments.
Secondary Outcome Measures 
Efficacy 
1.
Intra- and post-operative blood loss compared to the estimated volume of expected average blood loss 
and expected maximum blood loss in a comparable healthy individual with similar demographic 
characteristics as predicted preoperatively by the Investigator/surgeon at the following time points:

Intraoperative, from start until the end of surgery

Postoperative Day 1, from end of surgery to approximately 24 hours ±6 hours after surgery

Overall perioperative at discharge or 24 to 72 hours after the last perioperative treatment dose of 
BAX 802 (whichever is earlier)
2.
Proportion of major surgeries with good or excellent hemostatic outcome together with its 2-sided 
95% confidence interval
3.
Daily and total weight-adjusted administration of BAX 802 per subject
4.
Amount of blood products (e.g. whole blood, red blood cells,  platelets and plasma) transfused
For non-commercial use only

BAX 802
Page 7 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Safety
1.
Development of, and changes to, the titer of inhibitory and binding antibodies immunoglobulin G 
(IgG) and immunoglobulin M (IgM) to pFVIII
2.
Development of, and changes to, the titer of inhibitory and binding antibodies (IgG and IgM) to 
hFVIII
3.
Development of binding antibodies to BHK proteins
4.
Occurrence of thrombo-embolic events
5.
Incidence of severe allergic reactions (e.g., anaphylaxis)
6.
Incidence of other IP-related AEs
7.
Incidence of clinically significant changes in vital signs and routine laboratory parameters 
(hematology, clinical chemistry)
Exploratory Outcomes Measures
 
 
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Active Product
Dosage form: Injectable reconstituted solution of BAX 802, rpFVIII from 
which the B domain has been deleted.
Dosage frequency: Loading dose, followed by subsequent individualized 
dosing.
Mode of Administration: Intravenous bolus infusion (to the cubital vein is 
the recommended anatomical site of administration).
SUBJECT SELECTION
Targeted Accrual
Enroll approximately 12 evaluable subjects (2 of which will be adolescents 
≥ 12 to < 18 years old) for approximately 12 procedures.
Number of 
Groups/Arms/Cohorts
Single-arm
For non-commercial use only

BAX 802
Page 8 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Inclusion Criteria
1.
Subject requires a major or minor elective surgical, dental or other invasive procedure
2.
Subject is male and ≥ 12 to ≤ 75 years old at the time of screening
3.
Subject has provided signed informed consent (and assent for adolescent subjects, as applicable) in 
accordance with local regulatory requirements
4.
Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤ 2%) CHA with inhibitors 
to human FVIII (hFVIII), of ≥ 0.6 BU, as tested at screening at the central laboratory
5.
Subject is not currently receiving or has recently received (< 30 days) immune tolerance induction 
(ITI) therapy
6.
Subject has a Karnofsky performance score of ≥ 60 at screening
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and 
CD4+ count ≥ 200 cells/mm3 at screening
8.
Subject 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.
Subject is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
1.
The subject 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 FVIII (pFVIII) > 10 BU prior to surgery
5.
Platelet count < 100,000/µL at screening
6.
Subject has another active coagulation disorder, other than hemophilia A, as per the medical history
7.
Planned use of α-interferon with or without ribavarin 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 rpFVIII, or hamster or murine proteins
9.
Subject has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, 
fibrinolysis or disseminated intravascular coagulation (DIC).
10. Subject has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in 
another clinical study involving an IP or investigational device during the course of this study
11. Subject is unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the Investigator
For non-commercial use only

BAX 802
Page 9 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
STATISTICAL ANALYSIS
Sample Size Calculation
The sample size of approximately 12 surgeries/procedures in 12 evaluable male subjects (at least 5 major 
surgeries/procedures in 5 evaluable subjects), as defined in the protocol, was chosen to provide sufficient 
evidence of safety and effectiveness for this indication and is not based on statistical considerations. 
Evaluable subjects are defined as subjects who met all study entry criteria and who had at least 
1 hemostatic efficacy assessment.
Planned Statistical Analysis
Analysis Sets
The safety analysis set (SAS) will be comprised of all subjects who received any amount of BAX 802. The 
full analysis set (FAS) will be comprised of all surgeries with at least 1 available hemostatic assessment. 
The per-protocol analysis set (PPAS) will be comprised of all surgeries with evaluable ratings for all 
3 perioperative hemostatic efficacy assessments, whose subjects met all study entry criteria and had no 
major protocol violations that might impact hemostatic efficacy assessments.
Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy assessed 
intraoperatively and postoperatively by the surgeon at postoperative Day 1 (postoperative period, i.e., from 
end of surgery to 24 ±6 hours post-surgery) and perioperatively at 24 to 72 hours after the last perioperative 
treatment dose of BAX 802 is administered or discharge (whichever is earlier) by the surgeon and by the 
Investigator, and will be the sum of intraoperative, postoperative, and perioperative GHEA scores rated 
“excellent”, “good”, “fair” or “none”.
Wherever possible (except for intraoperative assessment), bleeding should be assessed by both operating 
surgeon and Investigator. To achieve the hemostatic efficacy success criteria, the study needs to achieve a 
≥70% rate of hemostatic efficacy assessments with an “excellent” or “good” outcome in at least 12 
procedures.
Due to the possibility of a subject undergoing multiple surgeries, the statistical analysis of the primary 
outcome measure will be reported on the by-surgery level (i.e., not by the number of subjects). In cases 
where two or more surgical procedures are performed in the same intraoperative settings (under the same 
anesthesia, e.g., bilateral knee replacement) the surgery will be counted as one surgery. Blood loss 
assessment from those surgeries will be assessed as one. In the event that the subject is planning to have 
additional surgery in the future, the subject will need to complete the study and be re-screened again (if 
> 3 months from the screening) to ensure that they continue to meet the eligibility criteria.
Point estimates and corresponding 2-sided exact Clopper-Pearson confidence intervals (CIs) at the 95% 
confidence level will be calculated for the rate of hemostatic efficacy assessments with excellent/good 
outcome for descriptive purposes.
The proportion of all surgeries and of all major surgeries with hemostatic success will be reported along 
with exact 95% CIs. A treatment success will be defined as a rating of excellent or good.
For non-commercial use only

BAX 802
Page 10 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The primary efficacy analysis will be based on the FAS population. As a supportive analysis, the same 
calculations will also be carried out on the PPAS population.
A sensitivity analysis based on the first surgery will be performed if more than 20% of subjects have 
multiple surgeries.
Any blood loss which is considered as unrelated bleeding (defined as any bleeding occurring at a different 
anatomical site other than the surgery site during the postoperative period) will not be taken into account 
for while making assessment of hemostatic efficacy for the primary efficacy measure.
Secondary Outcome Measures
Secondary hemostatic efficacy analysis:
Secondary outcome measures will be reported at the surgery level rather than the subject level. Descriptive 
statistics will be used to summarize the actual blood loss and transfusion requirements. The proportion of 
major surgeries with good or excellent hemostatic score together with its 2-sided 95% CI will be reported
for descriptive purposes. 
The summary of average daily and total weight-adjusted doses (average through postoperative 24 to 
72 hours after last perioperative treatment dose of BAX 802 or discharge [whichever is earlier]) of 
BAX 802 per subject as well as the occurrence of bleeding episodes will be provided using descriptive 
statistics. 
For unrelated bleeding episodes in the postoperative period, descriptive statistics will be used to summarize 
the overall hemostatic efficacy rating at 24 ±2 hours after initiation of treatment and at resolution of bleed
(if not resolved within 24 hours). The secondary efficacy analysis will be performed on the FAS only. 
Separate descriptive summaries of average daily and total weight-adjusted doses required to treat unrelated 
bleeding episodes and will be provided.
Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will 
be summarized by presenting the number and proportion of subjects having any AE, having an AE in each 
system organ class, and having each individual AE as reported by preferred term. In the summaries, AEs 
will be counted only once per patient. If a patient reports the same AE more than once, it will be counted 
with its worst severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be tabulated. In addition, the 
number of subjects who experienced AEs related to IP and the number of IP related AEs will be tabulated 
and subcategorized for thrombo-embolic events, inhibitory and total binding antibodies (IgG and IgM) to 
rpFVIII and hFVIII, and binding antibodies to BHK proteins.
An overview table for AEs will be provided, presenting the number of AEs, the number of subjects with 
AEs and the corresponding percent of subjects in total, and by seriousness and relationship to study 
treatment. An additional summary table will present the total number of (mild, moderate, severe) AEs by 
system organ class and preferred term with relationship to IP.
For non-commercial use only

BAX 802
Page 11 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Summary statistics over time will be presented for the continuous laboratory parameters. Descriptive 
statistics of changes from baseline (prior to BAX 802 loading dose before the surgery) by study visits will 
also be presented.
A frequency table of results of categorical laboratory parameters will be produced. Furthermore, laboratory 
abnormalities will be analyzed by shift tables where each subject will be counted only once with the worst 
grade in the summary tables.
Vital signs assessments as well as the corresponding changes from baseline will be summarized 
descriptively at each scheduled or unscheduled assessment.
For non-commercial use only

BAX 802
Page 12 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
4. TABLE OF CONTENTS
1. STUDY PERSONNEL.................................................................................................. 2
1.1 Authorized Representative (Signatory) / Responsible Party .............................. 2
1.2 Study Organization................................................................................................. 2
2. SERIOUS ADVERSE EVENT REPORTING........................................................... 3
3. SYNOPSIS..................................................................................................................... 4
4. TABLE OF CONTENTS ........................................................................................... 12
5. LIST OF ABBREVIATIONS .................................................................................... 17
6. BACKGROUND INFORMATION .......................................................................... 19
6.1 Description of Investigational Product ............................................................... 19
6.2 Clinical Condition/Indication .............................................................................. 19
6.3 Population to be Studied ...................................................................................... 21
6.4 Findings from Nonclinical and Clinical Studies................................................. 21
6.4.1 Finding from Nonclinical Studies................................................................. 21
6.4.2 Findings from Clinical Studies ..................................................................... 22
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 25
6.6 Compliance Statement.......................................................................................... 26
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 27
7.1 Study Purpose ....................................................................................................... 27
7.2 Primary Objective................................................................................................. 27
7.3 Secondary Objectives ........................................................................................... 27
7.4 Exploratory Objectives......................................................................................... 28
8. STUDY DESIGN......................................................................................................... 29
8.1 Brief Summary...................................................................................................... 29
8.2 Overall Study Design............................................................................................ 29
8.2.1 Types of Interventions................................................................................... 29
8.2.1.1 Major Surgeries ...................................................................................... 30
8.2.1.2 Minor Surgeries ...................................................................................... 30
8.2.2 Dose Selection Rationale ............................................................................... 31
8.3 Duration of Study Period(s) and Subject Participation .................................... 33
8.4 Outcome Measures ............................................................................................... 33
8.4.1 Primary Outcome Measure........................................................................... 33
For non-commercial use only

BAX 802
Page 13 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.2 Secondary Outcome Measures ..................................................................... 37
8.4.2.1 Efficacy .................................................................................................... 37
8.4.2.2 Safety........................................................................................................ 37
8.4.3 Exploratory Outcome Measures................................................................... 38
8.5 Randomization and Blinding............................................................................... 38
8.6 Study Stopping Rules............................................................................................ 38
8.7 Investigational Product(s) .................................................................................... 38
8.7.1 Packaging, Labeling, and Storage................................................................ 39
8.7.2 Reconstitution and Administration.............................................................. 40
8.7.3 Description of Treatment.............................................................................. 40
8.7.3.1 FVIII Maintenance Plan ........................................................................ 40
8.7.3.2 Perioperative Dosing .............................................................................. 41
8.7.3.3 Dosing Schedule and Requirements...................................................... 41
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics .................................... 47
8.7.5 Investigational Product Accountability ....................................................... 47
8.8 Source Data ........................................................................................................... 48
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 49
9.1 Inclusion Criteria.................................................................................................. 49
9.2 Exclusion Criteria................................................................................................. 49
9.3 Withdrawal and Discontinuation ........................................................................ 50
10. STUDY PROCEDURES .......................................................................................... 51
10.1 Informed Consent ............................................................................................... 51
10.2 Subject Identification Code................................................................................ 51
10.3 Screening and Study Visits................................................................................. 51
10.4 Study Periods....................................................................................................... 52
10.4.1 GHEA3 Visit................................................................................................. 52
10.4.2 Antibody Testing Visit................................................................................. 53
10.4.3 Unscheduled Visit ........................................................................................ 53
10.4.4 End of Study Visit........................................................................................ 53
10.5 Medications and Non-Drug Therapies.............................................................. 53
10.6 Rescue Medications............................................................................................. 54
10.7 Subject Completion/Discontinuation ................................................................ 55
10.8 Procedures for Monitoring Subject Compliance ............................................. 56
11. ASSESSMENT OF EFFICACY.............................................................................. 57
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score 57
11.2 Secondary Efficacy Endpoints........................................................................... 57
11.2.1 Blood Loss..................................................................................................... 57
11.2.2 Blood Transfusions ...................................................................................... 58
11.2.3 Bleeding Episodes ........................................................................................ 58
11.2.4 BAX 802 Administration............................................................................. 59
For non-commercial use only

BAX 802
Page 14 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical Site 
Bleeding Episodes.......................................................................................... 59
11.3 Factor VIII Activity............................................................................................ 60
11.3.1 Blood Sampling and Processing for FVIII Analysis................................. 61
12. ASSESSMENT OF SAFETY................................................................................... 62
12.1 Adverse Events.................................................................................................... 62
12.1.1 Definitions..................................................................................................... 62
12.1.1.1 Serious Adverse Event.......................................................................... 62
12.1.1.2 Suspected Unexpected Serious Adverse Reaction ............................. 63
12.1.1.3 Non-Serious Adverse Event ................................................................. 64
12.1.1.4 Unexpected Adverse Events................................................................. 64
12.1.1.5 Preexisting Diseases.............................................................................. 64
12.1.2 Assessment of Adverse Events.................................................................... 64
12.1.2.1 Severity .................................................................................................. 66
12.1.2.2 Causality................................................................................................ 66
12.1.2.3 Safety Reporting ................................................................................... 67
12.2 Urgent Safety Measures ..................................................................................... 68
12.3 Untoward Medical Occurrences........................................................................ 69
12.4 Non-Medical Complaints ................................................................................... 69
12.5 Medical, Medication, and Non-Drug Therapy History................................... 70
12.6 Physical Examinations........................................................................................ 70
12.7 Clinical Laboratory Parameters........................................................................ 71
12.7.1 Hematology, Clinical Chemistry, and Urinalysis...................................... 71
12.7.2 Viral Serology............................................................................................... 71
12.7.3 Immunogenicity ........................................................................................... 71
12.7.4 Assessment of Laboratory Values .............................................................. 72
12.7.4.1 Assessment of Abnormal Laboratory Values..................................... 72
12.7.5 Backup Samples and Biobanking............................................................... 72
12.8 Vital Signs............................................................................................................ 73
12.9 Karnofsky Performance Test............................................................................. 73
12.10 Special Treatment Considerations .................................................................. 74
13. STATISTICS............................................................................................................. 75
13.1 Sample Size and Power Calculations ................................................................ 75
13.2 Analysis Sets ........................................................................................................ 75
13.2.1 Safety Analysis Set....................................................................................... 75
13.2.2 Efficacy Datasets.......................................................................................... 75
13.2.2.1 Full Analysis Set.................................................................................... 75
13.2.2.2 Per-Protocol Analysis Set..................................................................... 75
13.3 Handling of Missing, Unused, and Spurious Data........................................... 76
13.4 Methods of Analysis............................................................................................ 76
13.4.1 Primary Outcome Measure......................................................................... 76
13.4.2 Secondary Outcome Measures ................................................................... 77
For non-commercial use only

BAX 802
Page 15 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.2.1 Secondary Hemostatic Efficacy Analysis............................................ 77
13.4.2.2 Safety Analysis ...................................................................................... 78
13.4.1 Exploratory Outcome Measures................................................................. 79
13.5 Planned Interim Analysis of the Study ............................................................. 79
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 79
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 80
15.1 Investigator’s Responsibility.............................................................................. 80
15.1.1 Investigator Report and Final Clinical Study Report.............................. 80
15.2 Training ............................................................................................................... 80
15.3 Monitoring........................................................................................................... 80
15.4 Safety Monitoring ............................................................................................... 81
15.5 Auditing ............................................................................................................... 81
15.6 Non-Compliance with the Protocol ................................................................... 81
15.7 Laboratory and Reader Standardization ......................................................... 81
16. ETHICS ..................................................................................................................... 82
16.1 Subject Privacy ................................................................................................... 82
16.2 Ethics Committee and Regulatory Authorities................................................ 82
16.3 Informed Consent ............................................................................................... 82
17. DATA HANDLING AND RECORD KEEPING................................................... 84
17.1 Confidentiality Policy ......................................................................................... 84
17.2 Study Documentation and Case Report Forms ............................................... 84
17.3 Document and Data Retention........................................................................... 84
18. FINANCING AND INSURANCE........................................................................... 85
19. PUBLICATION POLICY........................................................................................ 85
20. SUPPLEMENTS....................................................................................................... 86
20.1 Procedures per Study Period............................................................................. 86
20.2 Study Flow Chart................................................................................................ 92
20.3 Schedule of Study Procedures and Assessments.............................................. 93
20.4 Clinical Laboratory Assessments ...................................................................... 96
20.5 Global Efficacy Assessments Scores.................................................................. 99
20.6 Definitions.......................................................................................................... 100
20.6.1 Joint Bleeds................................................................................................. 100
20.6.2 Muscle Bleeds............................................................................................. 100
For non-commercial use only

BAX 802
Page 16 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES........................................................................................................ 101
22. SUMMARY OF CHANGES.................................................................................. 104
INVESTIGATOR ACKNOWLEDGEMENT............................................................ 109
INVESTIGATOR ACKNOWLEDGEMENT............................................................ 110
Tables
Table 1 Global Hemostatic Efficacy Assessment (GHEA) ............................................. 35
Table 2 Intraoperative Efficacy Assessment Scale (GHEA1) ......................................... 35
Table 3 Postoperative Efficacy Assessment Scale (GHEA2) (Postoperative Day 1)...... 36
Table 4 Overall Perioperative Efficacy Assessment Scale (GHEA3) (at Discharge or 
Within 24 to 72 hours after the last perioperative treatment dose of BAX 802
[whichever is earlier])............................................................................................... 36
Table 5 Dosing for Perioperative Management............................................................... 42
Table 6 BAX 802 Treatment Guidelines for Unrelated/Surgical Site Bleeding Episodes
................................................................................................................................... 46
Table 7 Efficacy Rating Scale for Treatment of Unrelated/Surgical Site Bleeding 
Episodes .................................................................................................................... 60
Table 8 Summary of Required Procedures for Baxalta Clinical Study 241502 .............. 86
Table 9 Schedule of Study Procedures and Assessments ................................................ 93
Table 10 Clinical Laboratory Assessments...................................................................... 96
Table 11 Combinations of Individual Efficacy Assessments (GHEA1, GHEA2, and 
GHEA3) and GHEA Score ....................................................................................... 99
Figures
Figure 1 Postoperative FVIII Monitoring........................................................................ 44
Figure 2 Visit Schedule.................................................................................................... 92
For non-commercial use only

BAX 802
Page 17 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
5. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
AHA
acquired hemophilia A
AICC
anti-inhibitor coagulant complex 
ALT
alanine aminotransferase
aPCC
activated prothrombin complex concentrate 
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
B19V
parvovirus B19
BHK
baby hamster kidney 
BU
Bethesda units
CI
confidence interval
CHA
Congenital Hemophilia A
CRF
case report form
CTA
Clinical Trial Agreement
DIC
disseminated intravascular coagulation
DSMB
data safety monitoring board
EBL
estimated blood loss
EC
Ethics Committee
ELISA
enzyme-linked immunosorbent assay
EU
European Union
FAS
full analysis set 
FDA
(United States) Food and Drug Administration
FVIII
Factor VIII
GCP
Good Clinical Practice
GHEA
Global Hemostatic Efficacy Assessment 
HAV
hepatitis A virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCT
hematocrit
HCV
hepatitis C virus
HEV
hepatitis E virus
hFVIII
human factor VIII 
HIV
human immunodeficiency virus
For non-commercial use only

BAX 802
Page 18 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Abbreviation
Definition
ICF
informed consent form 
ICH
International Council for Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
IgG
immunoglobulin G
IgM
immunoglobulin M
IP
investigational product
IPC
intermittent pneumatic compression 
IRB
Institutional Review Board
ITI
immune tolerance induction
ITT
intent-to-treat 
LMWH
low molecular weight heparin 
MedDRA
Medical Dictionary for Regulatory Activities 
NMC
Non-medical complaint
OR
operating room
PCR
polymerase chain reaction 
pFVIII
porcine factor VIII 
PK
pharmacokinetics
PPAS
per protocol (analysis set)
PT/INR
prothrombin time/international normalized ratio 
PV
plasma volume
rhFVIII
recombinant human factor VIII 
rpFVIII
recombinant porcine factor VIII 
RSI
Reference Safety Information
SAE
serious adverse event
SAER
serious adverse event report
SAP
statistical analysis plan 
SAS
safety analysis set 
SIC
subject identification code
SOC
standard of care
SUSAR
Suspected Unexpected Serious Adverse Reaction
TGA
thrombin generation assays 
U
unit(s)
ULN
upper limit of normal
US
United States
US CFR
US Code of Federal Regulations 
VIIa
activated factor VII 
WFH
World Federation of Hemophilia
For non-commercial use only

BAX 802
Page 19 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
The investigational product (IP), BAX 802, is a recombinant form of porcine factor VIII 
(rpFVIII) from which the B domain has been deleted. Deletion of the B domain does not 
affect the safety or efficacy of this recombinant form of human factor VIII (rhFVIII) in 
the treatment of hemophilia A. BAX 802 (rpFVIII) is being developed for the 
perioperative management of hemostasis in subjects with congenital hemophilia A 
(CHA) with inhibitors to human factor VIII (hFVIII) undergoing surgical or other 
invasive procedures. This rpFVIII was approved by the United States Food and Drug 
Administration (FDA) in 2014 for the treatment of bleeding episodes in adults with 
acquired hemophilia A (AHA; non hemophilia subjects developing spontaneous 
autoantibody inhibitors to hFVIII) under the trade name OBIZUR®.
6.2 Clinical Condition/Indication
Congenital hemophilia A is a congenital bleeding disorder caused by a deficiency or 
complete absence of coagulation factor VIII (FVIII) 1 and is referred to as CHA in order 
to differentiate it from AHA, which is a rare autoimmune disease with different bleeding 
patterns caused by immunoglobulin G antibodies that bind to specific domains on the 
FVIII molecule, in a person with a negative personal or family history of a 
coagulopathy.2
Overall, CHA accounts for about 80% of hemophiliacs. It affects all ethnic populations 
and its prevalence varies among different countries, but is estimated at a rate of 3 to 
20 cases per 100,000 population. The World Federation of Hemophilia (WFH) has 
estimated the total number of hemophilia cases at about 500,000 worldwide, of which 
one-third are diagnosed. The tendency to bleed in these subjects correlates with the 
plasma level of FVIII. This lifelong disorder has 3 clinical phenotypes (severe, moderate, 
and mild) that correlate with FVIII levels in plasma (< 1%, 1 to 5%, and 5 to 40%, 
respectively).3
Subjects with hemophilia A typically develop recurrent bleeding episodes. The most 
effective approach for treatment of acute bleeding episodes in subjects with hemophilia A 
is hFVIII replacement therapy.4,5 However, a major complication in the treatment of 
subjects with hemophilia A is the development of neutralizing antibodies (inhibitors) to 
hFVIII, which impair the efficacy of replacement therapy with hFVIII concentrates. 
Inhibitor development occurs more frequently among patients with severe or moderately 
severe hemophilia, and approximately 30% of patients with severe CHA develop 
inhibitors. In CHA patients with high-responding inhibitors, standard replacement 
For non-commercial use only

BAX 802
Page 20 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
therapy with FVIII concentrates is usually ineffective, resulting in poor control of 
hemorrhagic episodes. This, in turn, increases the risk of morbidity, mortality, orthopedic 
complications and disability, as well as reduced quality of life, compared with patients 
without inhibitors.6 Patients with CHA with inhibitors are also at risk of perioperative 
bleeding complications, since replacement of the missing coagulation factor is 
ineffective, presenting a therapeutic challenge in elective or emergency surgery.7
Currently Available Treatments and Unmet Medical Need
In CHA patients with transient, low-responding, and/or low-titers (< 5 Bethesda units 
[BU]/mL) inhibitors, increased doses of FVIII may be sufficient to overcome the 
inhibitor and provide hemostasis. In CHA patients with high-responding inhibitors 
(> 5 BU/mL), standard replacement therapy with FVIII concentrates is usually 
ineffective, resulting in poor control of hemorrhagic episodes. 
Alternative therapies are required for subjects with inhibitors who no longer respond to 
hFVIII replacement therapy. Recombinant activated factor VII (rFVIIa, NovoSeven®) 
and FEIBA (FVIII inhibitor bypassing activity; anti-inhibitor coagulant complex [AICC]) 
bypass the normal coagulation cascade and hence the FVIII inhibitors, and are therefore 
referred to as bypassing agents. Although these agents are able to manage bleeding in the 
presence of inhibitors, they do not attempt to restore the normal pathways of hemostasis, 
but instead boost thrombin generation despite a lack of platelet-surface FVIIIa–FIXa 
(‘tenase’) activity.6 The measurement of levels of factor VIIa in the subject’s plasma 
cannot be used as a clinically relevant surrogate marker and does not correlate with 
clinical outcome. Without an adequate biomarker, the dosage and treatment schedule 
cannot be clearly defined.8 In addition, the response to rFVIIa treatment may be 
inconsistent both from subject to subject and between different bleeds in the same 
subject. Because FEIBA is a human plasma fraction containing several coagulation 
factors, it has the potential to transmit human pathogens and may also cause 
thromboembolic events. Since the plasma fraction also contains hFVIII, it has been 
associated with a rise in hFVIII antibodies in approximately 20% of subjects.9
Moreover, as with rFVIIa, there is no validated biomarker that correlates with the clinical 
outcome with FEIBA treatment, although both thrombin generation assays (TGA) and 
whole blood viscoelastic assays have been evaluated for this purpose with some 
success.10
For non-commercial use only

BAX 802
Page 21 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The ultimate goal of treatment for these patients is eradication of the inhibitor through 
immune tolerance induction (ITI), which involves frequent and long-term administration 
of factor concentrates in an attempt to build tolerance in the immune system to FVIII or 
factor IX, and thus restore responsiveness to factor replacement therapy. However, 
ITI fails in approximately 30% of inhibitor patients with CHA.6
There is therefore a clinical need for an effective hemostatic agent for use in subjects with 
CHA who have inhibitors to hFVIII, and which allows monitoring of hemostatic efficacy 
based upon measurement of plasma FVIII activity levels, thus facilitating early 
determination of clinical benefit and the patient’s clinical status.
6.3 Population to be Studied
The study population will comprise of at least 12 procedures in 12 evaluable male 
subjects with CHA with inhibitors to hFVIII undergoing major or minor elective surgical, 
dental, or other invasive procedures (of which no more than 20% can be dental or other 
non-operative invasive procedures). Of 12 evaluable subjects, at least 2 will be 
adolescents (≥ 12 to < 18 years old), and in total there will be at least 5 major surgeries in 
5 evaluable subjects. Subjects will be considered to be eligible provided that they satisfy 
all of the inclusion criteria listed in Section 9.1 and none of the exclusion criteria listed in 
Section 9.2. In order to evaluate the activity of the product with respect to high-titer or 
high-responding inhibitors to hFVIII, at least 3 adult subjects with screening anti-hFVIII 
inhibitor titers of ≥ 5 BU will be enrolled in the study.
6.4 Findings from Nonclinical and Clinical Studies
6.4.1 Finding from Nonclinical Studies
Nonclinical studies were performed with rpFVIII to demonstrate hemostatic activity in 
2 animal models of hemophilia A (mice and dogs), local and systemic tolerance in a 
range of doses in single or repeat dose toxicology studies in monkeys, pharmacokinetics 
(PK) in dogs and monkeys, and immunogenicity in mice and monkeys.
Compatibility with the usual injection materials (needles, plastic syringes, and butterfly 
infusion needles with tubing) has been demonstrated. Studies in monkeys demonstrated 
the tolerability of repeated single daily injections of rpFVIII at doses up to 1000 U/kg, 
with injections at each dose level given once daily for 7 days. In 2 animal models of 
hemophilia A (mice and dogs), the hemostatic activity of rpFVIII was studied in 
comparison with Hyate:C. The rpFVIII was found to be efficacious in a dose-related 
fashion in controlling the bleeding associated with a standardized hemorrhagic insult. No 
animal studied was observed to have had an acute reaction to the injection of rpFVIII.
For non-commercial use only

BAX 802
Page 22 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.4.2 Findings from Clinical Studies
The safety and efficacy of rpFVIII was explored in 4 clinical trials prior to marketing 
approval:

OBI-1-101 (N=9): a Phase 1, multicenter, randomized, double-blinded, double-
dummy, parallel-group, comparison of the safety, tolerance, and PK study of 
rpFVIII versus Hyate:C was conducted.11

OBI-1-201 (N=9): a Phase 2, prospective, open-label, non-comparative study was 
conducted to assess the hemostatic activity of rpFVIII. Eligible subjects had a 
clinical diagnosis of hemophilia A with inhibitors to hFVIII, an anti-pFVIII
inhibitor antibody titer < 20 BU at screening, and an uncomplicated joint or soft 
tissue bleed, or other non-life threatening and non-limb threatening bleeding 
episode.12

OBI-1-301 (N=29): a multicenter, open-label, single-cohort, prospective, Phase 2/3
study of rpFVIII in subjects with acquired hemophilia to determine the hemostatic 
efficacy and safety of rpFVIII in the control of serious bleeding episodes.13

OBI-1-302 (terminated at N=1): a prospective, non-randomized, open-label study 
designed to assess treatment of serious bleeding episodes with rpFVIII in subjects 
with CHA who had developed anti-hFVIII inhibitors; this study was terminated by 
the sponsor after 1 subject was treated for administrative reasons, not due to safety 
or lack of efficacy concerns.
In all clinical studies, rpFVIII was generally well tolerated. There were no drug-related 
AEs reported in subjects who received rpFVIII in the Phase 1 study. One subject in the 
Phase 2 study (OBI-1-201) experienced pruritus (that resolved with diphenhydramine) 
that was possibly related to study drug. This AE occurred during the first bleeding 
episode, but the subject did not have a reaction during a second rpFVIII treated bleeding 
episode. In the Phase 1 and Phase 2 studies, no AEs led to treatment interruption, 
discontinuation from the study, or death. Vital signs, laboratory values, medical history 
and physical examination findings were within normal parameters for both studies and 
raised no safety concerns. 
In the Phase 2 study (OBI-1-201), the intent-to-treat (ITT) population consisted of 9 male 
subjects with CHA and with an inhibitor antibody to hFVIII. Six of the subjects (67%) 
were black and 3 subjects (33%) were Caucasian. The mean age of the subject population 
was 23.7 years (range: 14 to 34). The primary efficacy objective of the study was 
to evaluate the hemostatic efficacy of rpFVIII in the treatment of non-life/non-limb 
threatening bleeds in subjects with CHA and inhibitors.
For non-commercial use only

BAX 802
Page 23 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
A total of 25 bleeds in 9 subjects were treated with rpFVIII and all bleeds were 
successfully controlled with 8 or less injections of rpFVIII. The median number of 
rpFVIII injections administered per bleeding episode was 1.0 (range: 1 to 8) and the 
median time from bleeding onset to treatment was 5.67 hours (range: 1.5 to 20.0). Across 
all bleeding episodes the median total dose of rpFVIII per bleeding episode was 
224.1 U/kg (range: 50.0 to 1066.4). The median initial Treatment Dose (including the 
loading dose if applicable), was 159 U/kg (range: 50 to 576) and resulted in a median 
increase of FVIII plasma level of 16 % with the 1-stage clotting assay (range: 0.5% to 
427%) and a median increase of 17% with the chromogenic assay (range: 0% to 248%). 
Twenty of the 25 (80%) bleeds were controlled within 6 hours having been administered 
1 Treatment Dose of rpFVIII. For those 20 bleeds controlled with 1 Treatment Dose 
(including the loading dose if applicable), the median dose was 200.8 U/kg. The rpFVIII 
was well tolerated and of the reported AEs (n=61) only 18 AEs were considered 
treatment emergent. Two subjects reported an AE that was possibly related to study drug. 
One AE of itching/pruritus during the first bleeding episode but without reaction during a 
second rpFVIII treated bleeding episode. The second AE was a report of increased ALT 
and aspartate aminotransferase (AST), possibly associated with a confirmed hepatitis C 
infection, while it was uncertain whether the corresponding blood sample was taken 
before or after rpFVIII administration. Three subjects suffered treatment emergent SAEs 
but none were considered related to study drug. No reported AE led to treatment 
interruption, discontinuation from the study or death. Eight out of 9 (8/9, 89%) subjects 
developed anti-pFVIII antibodies following exposure to rpFVIII. In subjects who
received repeated rpFVIII treatment, higher anti-pFVIII titers did not affect efficacy or
safety and no increase in AEs or bleeding episodes were reported in the subjects with the 
highest titers. Regardless of the observed anti-pFVIII titers at pre-treatment or the 
obtained FVIII recovery values after treatment initiation, all bleeding episodes were 
successfully controlled. Analyses of baby hamster kidney (BHK; host cell line) antibody 
levels indicated that no subjects produced detectable levels of antibodies against BHK.
In the prospective, open-label trial (OBI-1-301), the efficacy of rpFVIII for the treatment
of serious bleeding episodes in subjects with AHA was investigated. The trial was 
conducted in 18 Caucasian, 6 African-American, and 5 Asian subjects diagnosed with 
AHA, having auto-immune inhibitory antibodies to hFVIII, and experiencing serious 
bleeding episodes that required hospitalization. Subjects with a prior history of bleeding 
disorders other than AHA, anti-pFVIII antibody titer > 20 BU, or in whom the bleeding 
episode was judged likely to resolve on its own, were excluded. One subject was 
considered evaluable at study entry; however, it was later determined that this subject did 
not have AHA, leaving 28 subjects evaluable for efficacy. Of the 28 subjects evaluable 
for efficacy, all subjects had a positive response to treatment for the initial bleeding 
For non-commercial use only

BAX 802
Page 24 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
episodes at 24 hours after dosing. A positive response was observed in 95% (19/20) of 
subjects evaluated at 8 hours and 100% (18/18) at 16 hours. In addition to response to 
treatment, the overall treatment success was determined by the Investigator based on 
his/her ability to discontinue or reduce the dose and/or dosing frequency of rpFVIII. A 
total of 24/28 subjects (86%) had successful treatment of the initial bleeding episode. Of 
those subjects treated with rpFVIII as first-line therapy, defined as no immediate previous 
use of anti-hemorrhagic agents prior to the first rpFVIII treatment, 16/17 subjects (94%) 
had eventual treatment success reported. Eleven subjects were reported to have received 
anti-hemorrhagics (eg, rFVIIa, activated prothrombin-complex concentrate, and 
tranexamic acid) prior to first treatment with rpFVIII. Of these 11 subjects, 8 had 
eventual successful treatment (73%). No related serious adverse reactions occurred. Non-
serious AEs related to treatment were noted and assessed by the Investigator in 6/29 
subjects (20.7%). One subject had mild tachycardia, hypotension and constipation. One 
subject had 2 instances of mild peripherally inserted central catheter (PICC) line 
occlusion. One subject had a mild hypofibrogenemia and 1 subject had moderate mental 
status changes. All of these adverse effects completely resolved. Two subjects developed 
anti- pFVIII inhibitors after infusion of study drug (range 8 to 51 BU) and were 
discontinued from treatment; however both subjects had a positive response to treatment 
at the 24-hour primary endpoint assessment. An investigation was conducted by the 
sponsor and, in summary, the 2 incidences of anti-pFVIII inhibitors were considered 
related to rpFVIII treatment, while the other non-serious treatment-related adverse events 
were considered as unlikely to be related to rpFVIII. Anti-pFVIII inhibitors were detected 
prior to infusion in 10/29 patients (range 0.8 to 29 BU). All of these subjects had a 
positive response at 24 hours post-rpFVIII first infusion. No anti-BHK antibodies were 
observed in any of the 29 treated subjects.
At the time of OBIZUR® marketing approval, the clinical trial data indicated that rpFVIII 
was well tolerated and had demonstrated effectiveness in the control of bleeding in study 
subjects. Cumulatively (patient exposure from 01 Oct 2014 through 31 Oct 2016), 
approximately 16,424,000 units (U) of OBIZUR® were sold worldwide. Median (range) 
treatment dose per bleeding episode was 94,500 (35,256 to 182,700), and the estimated 
number of patient-years worldwide to OBIZUR® was approximately 347.6 (179.8 to 
931.6). As of 11 Nov 2016, there have been 20 post-marketing serious case reports with 
36 AEs. No adverse reactions other than those observed in clinical trials have been 
observed in the post marketing setting. The reports were consistent with the known safety 
profile of OBIZUR®.i
                                                
i Obizur Periodic Safety Update Report/Periodic Benefit-Risk Evaluation Report (PSUR/PBRER), 
reporting interval 12 MAY 2016 to 11 NOV 2016.
For non-commercial use only

BAX 802
Page 25 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Porcine FVIII (Hyate:C), derived from porcine plasma, had been used successfully 
starting in the 1980s to achieve hemostasis in the presence of anti-hFVIII inhibitors, as 
the antibodies generally have low immunological cross-reactivity with pFVIII.14
However, the number of hemophilia A subjects who were appropriate candidates to 
receive Hyate:C was limited by the degree to which their anti-hFVIII antibodies 
cross-reacted with pFVIII and the presence of any anti-pFVIII inhibitors. While a median 
inhibitor cross-reactivity observed to porcine VIIIC was only 15%, an absent, 
intermediate, or brisk specific anti-porcine anamnestic response was observed in 29%, 
40%, and 31% of patients, respectively.15 The commercial production of Hyate:C was 
discontinued in 2005 due to problems with sourcing suitable porcine plasma, but not due 
to any safety or efficacy concerns. 
BAX 802 is a B-domain deleted rpFVIII glycoprotein which is being developed for the 
perioperative management of hemostasis in subjects with CHA with FVIII inhibitors 
undergoing surgical or other invasive procedures. B-domain deleted rpFVIII glycoprotein 
has been extensively studied. BAX 802 (as marketed OBIZUR®) is not currently 
indicated for the treatment of CHA.16
OBIZUR® was approved based on the safety and efficacy data from 28 subjects with 
AHA treated with B-domain deleted rpFVIII glycoprotein in the Phase 2/3 open-label 
clinical study OBI-1-301. The safety, hemostatic activity, and PK profile of B-domain 
deleted rpFVIII glycoprotein was also supported by results of an open-label Phase 2 study 
in patients with CHA with inhibitors (Clinical Study Report OBI-1-201), and a 
randomized Phase 1 study comparing B-domain deleted rpFVIII glycoprotein with a 
plasma-derived pFVIII (CSR OBI-1-101). 
The data supported the use of B-domain deleted rpFVIII glycoprotein to treat serious 
bleeding episodes in AHA patients (Section 6.4.2). It was demonstrated that B-domain 
deleted rpFVIII glycoprotein provides benefit to AHA patients who are unresponsive to 
alternative agents with an improved dosing algorithm. It was possible to monitor 
hemostatic efficacy based upon measurement of plasma FVIII activity levels, thus 
facilitating early determination of clinical benefit and the patient’s clinical status. An 
additional benefit to the patient was that it was possible to adjust the dose based on the 
FVIII levels rather than follow fixed dosing, ensuring that adequate doses were 
administered to achieve hemostasis.
For non-commercial use only

BAX 802
Page 26 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The most frequently reported adverse reaction in patients with AHA was the development 
of inhibitors to pFVIII.16
Overall, efficacy and safety clinical data for OBIZUR supported a favorable benefit/risk 
determination for the proposed indication of treatment of bleeding episodes in adults with 
AHA.
These data support the investigation of efficacy and safety of BAX 802 in subjects with 
CHA with inhibitors undergoing surgical or other invasive procedures. 
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council 
for Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), 
Title 21 of the United States (US) Code of Federal Regulations (US CFR), the European 
Union (EU) Directives 2001/20/EC and 2005/28/EC, and applicable national and local 
regulatory requirements.
For non-commercial use only

BAX 802
Page 27 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to evaluate the efficacy and safety of BAX 802 in males with 
CHA with inhibitors who are undergoing major or minor elective surgical, dental, or 
other invasive procedures. 
7.2 Primary Objective
The primary objective of the study is to evaluate the perioperative hemostatic efficacy of 
BAX 802 in male subjects with CHA with inhibitors to hFVIII undergoing major or 
minor elective surgical, dental, or other invasive procedures as determined by the Global 
Hemostatic Efficacy Assessment (GHEA) score.
7.3 Secondary Objectives
The secondary objectives of the study are:
1.
To determine the safety of BAX 802 used in the perioperative setting by assessing:

The development of and change in titer of anti-pFVIII and anti-hFVIII 
antibodies (binding and neutralizing), and development of binding antibodies 
to BHK proteins

The occurrence of thrombo-embolic events and/or allergic reactions to 
BAX 802

The occurrence of AEs related to BAX 802

The occurrence of clinically significant changes in vital signs and routine 
laboratory parameters related to BAX 802
2.
To determine the intraoperative, postoperative, and overall perioperative blood loss, 
compared to the estimated volume of expected average and maximum blood loss in 
a comparable healthy individual as predicted preoperatively by the 
Investigator/surgeon
3.
To determine the proportion of major surgeries with good or excellent hemostatic 
score
4.
To determine the daily and total weight-adjusted administration of BAX 802 per 
subject
For non-commercial use only

BAX 802
Page 28 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7.4 Exploratory Objectives
The exploratory objectives of the study are:
 
 
 
 
 
 
For non-commercial use only

BAX 802
Page 29 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8. STUDY DESIGN
8.1 Brief Summary
This study is a Phase 3, prospective, single-arm, open-label, uncontrolled, multicenter 
study to evaluate the efficacy and safety of BAX 802 in at least 12 procedures in 
12 evaluable male subjects ≥12 to ≤75 years old with CHA with inhibitors to hFVIII 
who are undergoing major and minor surgical, dental or other invasive procedures. At 
least 5 of the procedures must be major surgeries in 5 evaluable subjects, of which no 
more than 20% can be dental or other non-operative invasive procedures (see 
Section 8.2.1), and at least 3 adult subjects with screening anti-hFVIII titers of ≥5 BU for 
inhibitors to human FVIII will be enrolled in the study. At least 2 adolescents (≥12 to 
< 18 years old) will be enrolled in the study.
8.2 Overall Study Design
The dose and frequency of BAX 802 during the preoperative, intraoperative, and 
postoperative periods should follow a proposed substitution plan provided by the 
Investigator to the medical monitor prior to surgery and adjusted based on regular FVIII 
activity measurements (see Section 8.7.3.1). The regimen will depend on the type of 
surgery performed and the intensity of the hemostatic challenge.
Elective surgical procedures will prospectively be defined as major or minor by the 
Investigator/surgeon and agreed with the medical director/designee, based on the protocol 
guidance and definitions and in consideration of each subject’s characteristics. 
Emergency surgeries are not in the scope of this study. Subjects may undergo more 
than 1 surgery or 2 parallel surgeries, such as bilateral knee replacement. For subjects 
undergoing multiple surgeries (other than parallel surgeries), the End of Study visit
should be completed for the first surgery and then subject needs to be re-screened
(Section 10.3) for the next surgery.
The study will be divided into 5 periods: Screening, Preoperative, Intraoperative, 
Postoperative, and End of study (Table 8). The study will be conducted at multiple sites 
in North America, Europe, and South Africa.
The overall study design is illustrated in Figure 2. 
8.2.1 Types of Interventions
Elective surgeries and other invasive procedures will prospectively be defined by the 
Investigator/surgeon as major or minor based on the definitions and examples provided in 
Section 8.2.1.1 and Section 8.2.1.2, respectively, taking into consideration each 
individual patient’s characteristics and agreement with the sponsor.
For non-commercial use only

BAX 802
Page 30 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.2.1.1 Major Surgeries
Major surgeries include surgeries that require moderate or deep sedation, general 
anesthesia, or major conduction blockade for patient comfort. This generally refers to 
major orthopedic (e.g., joint replacement), major abdominal, intracranial, cardiovascular, 
spinal and any other surgery which has a significant risk of large volume blood loss 
(> 500 mL) or blood loss into a confined anatomical space. Extraction of at least 3 teeth 
or extraction of the third molar are generally considered as major. Examples include:

bone fixation for fracture

hip and knee replacement (arthroplasty)

arthrodesis (joint fusion)

open synovectomy

osteotomy

liver biopsy

pseudotumor removal

hardware removal (plates and intramedullary nails)
Major surgeries/interventions are expected to require clinical surveillance or hospital 
treatment > 3 days after the surgery/intervention. 
8.2.1.2 Minor Surgeries
Minor surgeries include surgeries that can be safely and comfortably performed on a 
patient who has received local or topical anesthesia, without more than minimal 
preoperative medication or minimal preoperative medication or minimal intraoperative 
sedation. The estimated total blood loss should be < 500 mL and the likelihood of 
complications requiring hospitalization or prolonged hospitalization should be remote. It 
refers to interventions such as removal of skin lesions, arthroscopy, minor dental 
procedures or dental extractions. Examples include:

removal of skin lesions

minor dental procedures or dental extractions (except extraction of 3 or more teeth 
or third molar extraction)

placement and/or removal of central venous catheters

synoviorthesis and arthrocentesis
For non-commercial use only

BAX 802
Page 31 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

arthroscopy

nerve release

removal of osteophytes and small cysts 
Minor surgeries/interventions are expected to require clinical surveillance or hospital 
treatment ≤3 days after the surgery/intervention
8.2.2 Dose Selection Rationale
Background
This is a Phase 3, multicenter, single-arm, open-label study of the efficacy and safety of 
B-domain deleted rpFVIII (BAX 802) in the perioperative management of hemostasis in 
subjects with CHA who have inhibitors and are undergoing surgical or other invasive 
procedures. The rpFVIII temporarily replaces the inhibited FVIII that is needed for 
effective hemostasis in CHA patients who have developed inhibitors to hFVIII. The 
principle of using pFVIII is based on its low cross-reactivity with anti-hFVIII antibodies 
due to sequence variations between human and pFVIII in the A2 and C2 domains, the 
main targets of FVIII inhibitors. The rpFVIII concentrate is predicted to have an 
advantage over human-derived FVIII in CHA patients who have inhibitors since previous 
studies demonstrated that the antibodies have a median of only 15% cross-reactivity with 
plasma-derived pFVIII.17
Regulatory approval for rpFVIII for the treatment of bleeding episodes in adults with 
AHA was received for OBIZUR®; per the product label, the initial dose of OBIZUR® is 
200 U/kg, with subsequent dosing dependent on the location and severity of bleeding 
episode, target FVIII levels, and the patient’s clinical condition.16
Influence of Anti-pFVIII Inhibitor Titer on the Loading Dose
Anti-pFVIII inhibitors are neutralizing antibodies against pFVIII that neutralize the 
pFVIII, and thereby reduce its hemostasis effect. Anti-pFVIII inhibitors can be quantified 
in plasma by the Bethesda assay, which measures the ability of the patient’s plasma to 
neutralize exogenous pFVIII when incubated together.
The amount of BAX 802 required to neutralize the anti-pFVIII activity is factored in. 
A BU is defined as the amount of anti-pFVIII inhibitor in a plasma sample which will 
neutralize 50% of 1 unit of BAX 802 in normal plasma after 2 hour incubation at 37°C. 
For non-commercial use only

BAX 802
Page 32 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Only the inhibitor that is distributed in the plasma volume (PV) is initially available to 
neutralize the infused FVIII; PV is calculated using the following formula:
PV = Blood Volume × (1 – [hematocrit{HCT}%/100])
Normal blood volume is approximately 80 mL/kg for adults.
Therefore, PV = 80 × (1 – [HCT%/100]).
One BU of anti-pFVIII inhibitor will neutralize 50% of 1 unit of BAX 802; therefore, it is 
assumed that 0.5 U FVIII will be required for each 1 BU of inhibitor. The amount of 
BAX 802 required to neutralize the anti-pFVIII activity can be estimated using the 
following:
Body weight × 80(1 - [HCT%/100]) × 0.5 × anti-pFVIII inhibitor titer (BU/mL) = 
body weight × 40(1-[HCT%/100]) × anti-pFVIII inhibitor titer (BU/mL).
Proposed Dosing Regimen of BAX 802 in Study BAX 802 Surgery
The dosing scheme to be used in Study BAX 802 Surgery is presented in Section 8.7.3.3.
The loading dose of BAX 802 (in U) for a CHA subject with inhibitors undergoing major 
surgery is calculated using the following formula:
[80 × body weight (kg)] U + [body weight (kg) × 40(1-[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU/mL)] U
For example, for a 70 kg subject undergoing major surgery and having HCT 45% and 
anti-pFVIII inhibitor titer 3 BU/mL, the loading dose of BAX 802 will is calculated as 
follows: 
[80 (70)] U + [70 × 40(1-[45/100]) × 3] U = 10,220 U
This dosing scheme should reasonably predict the loading dose before surgery that will 
provide sufficient FVIII levels needed for effective hemostasis.
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels achieved, and will require empirically based 
adjustments until hemostasis is achieved (Table 5).
This dosing algorithm is essentially equivalent to that proposed by Kasper (2004) when 
using FVIII in the treatment of patients with low titer inhibitors.18
For non-commercial use only

BAX 802
Page 33 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study will be approximately 28 months from study initiation 
(i.e., first subject enrolled) to study completion (i.e., last subject, last visit). The 
recruitment period is expected to be approximately 24 months. A subject is considered 
enrolled if he has signed the Informed Consent Form.
The duration of subject participation depends on the nature of the invasive procedure: it 
will run from the signing of the informed consent until completion of the End of Study 
Visit 42 ± 7 days after last perioperative dose of BAX 802 (end of surgery = Day 0), 
unless prematurely discontinued. Study completion is defined by the End of Study Visit.
8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is the proportion of all surgical, dental, or other invasive 
procedures with a “good” or “excellent” response as measured by GHEA score (Table 1), 
which is composed of 3 individual ratings:

GHEA1: Assessment of intraoperative (Day 0) hemostatic efficacy of BAX 802
performed by the operating surgeon (see Table 2) at the end of surgery

GHEA2: Assessment of postoperative hemostatic efficacy of BAX 802 at 
postoperative Day 1 (approximately 24 hours [± 6 hours] post-surgery) performed 
by the operating surgeon. (Note: If a patient is discharged < 24 hours following 
surgery, then the GHEA2 hemostatic efficacy assessment will require a return visit 
the following day) (see Table 3)

GHEA3: Assessment of overall perioperative hemostatic efficacy of BAX 802 at 
the GHEA3 Visit (discharge or within 24 to 72 hours after the last perioperative 
treatment dose of BAX 802 [whichever is earlier]), performed by the Investigator, 
and where possible, also by the operating surgeon. Assessment by both is strongly 
recommended. In cases where there are differing assessments, the Investigator’s 
assessment will be used (see Table 4). 
(Note: In cases such as minor surgeries/procedures, there might be a possibility that the 
subject is discharged < 24 hours following the surgery/procedure but continues receiving
BAX 802 in hospital (e.g., day hospital) setting. In these cases, the GHEA2 hemostatic 
efficacy assessment should be performed the following day. Also, the GHEA3 Visit 
should be performed within 24 to 72 hours after the last perioperative treatment dose of 
BAX 802. Both GHEA2 and GHEA3 assessments can be performed on the day after the 
surgery/procedure if the subject does not need any further BAX 802 administration for 
perioperative management.)
For non-commercial use only

BAX 802
Page 34 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Prior to the surgery, the surgeon/Investigator will predict the estimated volume (in mL) of 
the expected blood loss for the planned surgical intervention in a hemostatically normal 
individual of the same sex, age, and stature as the study subject, for intraoperative, 
postoperative, and overall perioperative time periods. Every effort should be made to 
predict the volume as precisely as possible, also taking into account, for example, the use 
of a tourniquet or placement of a postoperative drain and whether or not suction is used.
The estimate will be for the intraoperative time period and from completion of the 
procedure until approximately 24 hours post-surgery and for the overall perioperative 
period (see Section 11.2.1).
The scores of each of the 3 individual ratings (GHEA1, GHEA2, and GHEA3) described 
above, will be added together to form a GHEA score according to Table 1. For a GHEA 
score of 7 to be rated “excellent” no individual assessment score should be less than 2 
(i.e., one individual assessment score must be 3 and the other two individual assessment 
scores must be 2). The only other option to achieve a GHEA score of 7 is for two
individual assessment scores of 3 and one individual assessment score of 1. Although this 
GHEA score will not qualify for a rating of “excellent,” the GHEA score will satisfy the 
definition of “good,” (with no individual assessment score less than 1). All possible 
combinations of the individual assessment scores and their related ratings are provided in 
Supplement 20.5. 
For surgeries with up to 2 missing hemostatic assessments that did not necessitate rescue 
therapies, the rating of “fair” will be imputed for these missing data. These surgeries will 
be included in the full analysis set (FAS). The assessment of primary outcome measure 
(GHEA score) should only account for the blood loss related to the surgery and exclude 
any blood loss which is considered as unrelated bleeding (defined as any bleeding 
occurring at a different anatomical site than the surgery site during the postoperative 
period, see Section 11.2.5).
For non-commercial use only

BAX 802
Page 35 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 1
Global Hemostatic Efficacy Assessment (GHEA)
Assessment
GHEA Score
Excellent
7a to 9
(with no category scored < 2)
Good
5 to 7a
(with no category scored < 1)
Fair
3 to 4
(with no category scored < 1)
None
0 to 2 (or at least one category scored 0)
a For a GHEA score of 7 to be rated “excellent” (with no individual assessment scores less than 2), at 
least 1 individual assessment score must be 3 and the other 2 individual assessment scores must be at 
least 2; otherwise a score of 7 is rated “good”.
Table 2
Intraoperative Efficacy Assessment Scale (GHEA1)
At the end of surgery, the operating surgeon will assess the intraoperative hemostatic 
efficacy
Rating
Criteria
Score
Excellent
Intraoperative blood loss was less than or equal to that expected for the type of 
procedure performed in a non-hemophilic population (≤100%)
3
Good
Intraoperative blood loss was up to 50% more than expected for the type of 
procedure performed in a non-hemophilic population (101 to 150%)
2
Fair
Intraoperative blood loss was more than 50% of that expected for the type of 
procedure performed in a non-hemophilic population (> 150%)
1
None
Uncontrolled hemorrhage that was the result of inadequate therapeutic response 
despite proper dosing, necessitating rescue therapy or other FVIII products
0
For non-commercial use only

BAX 802
Page 36 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 3
Postoperative Efficacy Assessment Scale (GHEA2) (Postoperative Day 1)
On postoperative Day 1 (24 ± 6 hours post-surgery), the operating surgeon will assess the 
postoperative hemostatic efficacy
Rating
Criteria
Score
Excellent
Postoperative blood loss was less than or equal to (≤100%) that expected for 
the type of procedure performed in a non-hemophilic population
3
Good
Postoperative blood loss was up to 50% more (101% to 150%) than expected 
for the type of procedure performed in a non-hemophilic population
2
Fair
Postoperative blood loss was more than 50% (> 150%) of that expected for the 
type of procedure performed in a non-hemophilic population
1
None
Significant postoperative bleeding that was the result of inadequate therapeutic 
response despite proper dosing, necessitating rescue therapy or other FVIII 
products
0
Table 4
Overall Perioperative Efficacy Assessment Scale (GHEA3) (at Discharge or Within 
24 to 72 hours after the last perioperative treatment dose of BAX 802 [whichever is 
earlier])
At discharge or within 24 to 72 hours after the last perioperative treatment dose of BAX 802 
(whichever is earlier), the postoperative efficacy assessment will be performed by the 
Investigator, and where possible, also by the operating surgeon
Rating
Criteria
Score
Excellent
Overall perioperative blood loss was less than or equal to (≤100%) that 
expected for the type of procedure performed in a non-hemophilic population,
Required blood components for transfusions were less than or similar to that 
expected in non-hemophilic population
3
Good
Overall perioperative blood loss was up to 50% more (101% to 150%) than 
expected for the type of procedure performed in a non-hemophilic population
Required blood components for transfusions were less than or similar to that 
expected in non-hemophilic population
2
Fair
Overall perioperative blood loss was more than 50% of that expected for the 
type of procedure performed in a non-hemophilic population (> 150%)
Required blood components transfusions were greater than that expected in 
non-hemophilic population
1
None
Significant overall perioperative bleeding that was the result of inadequate 
therapeutic response despite proper dosing, necessitating rescue therapy or 
other FVIII products
Required blood components for transfusions were substantially greater than that 
expected in non-hemophilic population
0
For non-commercial use only

BAX 802
Page 37 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Hemostatic efficacy success is defined as “excellent” or “good “outcome for ≥ 70% of 
hemostatic efficacy assessments.
8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy
1.
Intra- and post-operative blood loss compared to the estimated volume of expected 
average blood loss and expected maximum blood loss in a comparable healthy 
individual with similar demographic characteristics as predicted preoperatively by 
the Investigator/surgeon at the following time points:

Intraoperative, from start until the end of surgery

Postoperative Day 1, from end of surgery to approximately 24 hours 
(± 6 hours) after surgery

Overall perioperative at discharge or 24 to 72 hours after the last perioperative 
treatment dose of BAX 802 (whichever is earlier)
2.
Proportion of major surgeries with good or excellent hemostatic score
3.
Daily and total weight-adjusted administration of BAX 802 per subject
4.
Amount of blood products (e.g., whole blood, red blood cells, platelets and plasma) 
transfused
8.4.2.2 Safety
1.
Development of, and changes to, the titer of inhibitory and binding antibodies (IgG 
and IgM) to pFVIII
2.
Development of, and changes to, the titer of inhibitory and binding antibodies (IgG 
and IgM) to hFVIII
3.
Development of binding antibodies to BHK proteins
4.
Occurrence of thrombo-embolic events
5.
Incidence of severe allergic reactions (e.g., anaphylaxis)
6.
Incidence of other IP-related AEs
7.
Incidence of clinically significant changes in vital signs and routine laboratory 
parameters (hematology, clinical chemistry)
For non-commercial use only

BAX 802
Page 38 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.4.3 Exploratory Outcome Measures
 
 
 
 
 
8.5 Randomization and Blinding
This is a non-randomized, open-label, active treatment clinical study.
8.6 Study Stopping Rules
The study will be halted (enrollment stopped), pending further review by the external 
data safety monitoring board (DSMB) and sponsor, if 1 or more of the following criteria 
are met:
1.
Two or more subjects develop a severe anaphylactic reaction or any other serious 
adverse event (SAE) related to BAX 802 that would not be expected 
2.
The occurrence of Suspected Unexpected Serious Adverse Reaction (SUSAR)
3.
Other AEs that are deemed to pose unacceptable risks to subjects.
The study may be terminated, if 1 or more of the following criteria are met:
1.
The sponsor decides to terminate the study based upon DSMB recommendation or 
its own assessment of safety
2.
The sponsor decides to terminate the study at any time for administrative reasons.
8.7 Investigational Product(s)
The IP, BAX 802, is a recombinant purified form of rpFVIII from which the B domain 
has been deleted and replaced with a 24 amino acid linker. Recombinant pFVIII 
(BAX802) is expressed as a glycoprotein by a genetically engineered BHK cell line. 
The molecular weight of rpFVIII is approximately 175 kDa (based on its 1448 amino 
acid sequence) and has 86% pair-wise sequence homology with hFVIII. 
For non-commercial use only

BAX 802
Page 39 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
BAX 802 will be supplied as white lyophilized powder in 3 mL glass vials containing 
nominally 500 units per vial for reconstitution with 1.0 mL sterile water for injection. 
8.7.1 Packaging, Labeling, and Storage
BAX 802 will be supplied in a lyophilized form. For specific instructions for 
reconstitution, please refer to the Pharmacy Manual. A sufficient quantity of BAX 802
will be supplied to each study site, as well as an acknowledgement of receipt form.
The core label texts for all packaging units will be translated or adjusted, to be in 
compliance with applicable regulatory requirements, national laws in force and in 
accordance with the local languages. Minimally each vial will bear a label with the 
following information:

Sponsor name

Study number

Pharmaceutical dosage form

Route of administration

Name of IP and actual quantity of dose units

Batch number

Space on which to record the subject number

The statement ‘For clinical trial use only’ or ‘Caution: new drug limited by Federal 
Law to investigational use’ or ‘To be used only by a qualified Investigator’, as 
appropriate

Name, address and telephone number of the Sponsor, Contract Research 
Organization or Investigator, if appropriate

Storage conditions

Expiry or manufacturing date, as appropriate
The Investigator or designee will only dispense BAX 802 to subjects included in this 
study.
For non-commercial use only

BAX 802
Page 40 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
BAX 802 should be kept refrigerated at 2°C to 8°C (36°F to 46°F). The following 
precautions should be taken:

Do not freeze

Do not use if frozen, even if it has been thawed

Do not use beyond the expiration date printed on the carton or vial

Do not use after > 3 hours of reconstitution.
8.7.2 Reconstitution and Administration
The reconstitution procedures for BAX 802 are detailed in the Pharmacy Manual. 
Reconstituted BAX 802 should be kept and administered at room temperature and must 
be administered within 3 hours of reconstitution.
BAX 802 will be administered as an intravenous bolus infusion to the cubital vein per the 
dosing schema for major and minor surgeries (Table 5).
8.7.3 Description of Treatment
8.7.3.1 FVIII Maintenance Plan
Based on the category (minor or major) and type of surgery and prior to intervention, the 
Investigator should outline the expected FVIII maintenance plan with target peak and 
trough levels covering the surgical, dental or invasive procedure until expected wound 
healing. The FVIII maintenance plan should be communicated to the medical 
director/designee to ensure that the recommendations regarding FVIII target levels as 
provided in the protocol are followed (see Table 5). Each FVIII maintenance plan for 
major surgeries requires prior approval of the medical director. The FVIII levels 
measured intra/postoperatively will be compared with the FVIII maintenance plan. Slight 
deviations from the predefined plan are allowed based on Investigators clinical judgment 
and/or available laboratory FVIII data.
It is recommended that the turnaround time for FVIII activity results from the local 
laboratories are ≤2 hours so that dosing decisions could be made and subjects are dosed 
adequately.
For non-commercial use only

BAX 802
Page 41 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3.2 Perioperative Dosing
Adjustments to the dose and frequency of BAX 802 dosing during the intra- and 
postoperative period should follow the maintenance plan provided by the Investigator
prior to surgery. Adjustments must be based on regular FVIII activity measurements 
determined at pre- and post-dosing of BAX 802 and will depend on the type of the 
surgery performed and the intensity of the hemostatic challenge.
8.7.3.3 Dosing Schedule and Requirements
8.7.3.3.1 General
As described in Section 8.2.2, the loading dose will be calculated according to the 
following formula:
Loading dose of BAX 802 (administered approximately 1 to 2 hours prior to the 
surgery):

Major Surgery:
[80 × body weight (kg)] U + [body weight (kg) × 40(1-[HCT%/100]) x anti-pFVIII 
inhibitor titer (BU/mL)] U

Minor Surgery:
[50 × body weight (kg)] U + body weight (kg) × 40(1-[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU/mL)] U
For example, for a 70 kg subject undergoing major surgery and having HCT 45% and 
anti-pFVIII inhibitor titer 3 BU/mL, the loading dose of BAX 802 will be calculated as 
follows: 
80 (70) + 70 × 40(1-[45/100]) × 3 = 10,220 U
Subsequent doses, dosing frequency, and duration of treatment will be based on clinical 
judgment and measured FVIII levels, and will require empirically based adjustments until 
hemostasis is achieved based on the following calculation below (Table 5):

Required (subsequent) dose (U) = [body weight (kg) × desired FVIII rise 
(U/dL or % of normal)]/1.2 (U/kg per U/dL).
For non-commercial use only

BAX 802
Page 42 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 5
Dosing for Perioperative Management
Type of 
Surgery
Recommended FVIII Level
(% of normal or U/dL)
Loading Dose (U)
Subsequent Dose
(U)
Major
(see 
Section 8.2.1.1)
Prior to surgery: ≥80%
Postoperative up to 72 hours 
(if not yet discharged and 
GHEA3 not yet performed): 
≥80%
Postoperative Day 4 – Day 7
(if not yet discharged and 
GHEA3 not yet performed): 
≥50% 
After Postoperative Day 8 (if 
not yet discharged and 
GHEA3 not yet performed): it 
is recommended that the FVIII 
levels do not fall below 30% 
(left to the discretion of the 
Investigator depending on the 
postoperative course)
[80 × body weight (kg)] U + 
[body weight (kg) ×
40(1-[HCT%/100]) × anti-
pFVIII inhibitor titer 
(BU/mL)a] U, administered 
approximately 1 to 2 hours
prior to the surgery
Titrate subsequent 
doses to maintain 
recommended FVIII 
trough levels and 
individual clinical 
response using 
following formula:
Required dose (U) 
= [body weight (kg) 
× desired FVIII rise 
(U/dL or % of 
normal)]/1.2 (U/kg 
per U/dL)
Minor 
(see 
Section 8.2.1.2)
Prior to surgery: ≥50%
Postoperative up to 72 hours 
(if not yet discharged and 
GHEA3 not yet performed): 
≥50%
After Postoperative Day 4 (if 
not yet discharged and 
GHEA3 not yet performed): it 
is recommended that the FVIII 
levels do not fall below 30% 
(left to the discretion of the 
Investigator depending on the 
postoperative course)
[50 × body weight (kg)] U + 
[body weight (kg) × 40(1-
[HCT%/100]) × anti-pFVIII 
inhibitor titer (BU/mL)a] U, 
administered approximately 1 
to 2 hours prior to the surgery
a Anti-pFVIII inhibitor titer and hematocrit information available from screening laboratory result will be 
used.
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
For non-commercial use only

BAX 802
Page 43 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If at any time during the study, a subject does not respond to BAX 802 therapy as 
anticipated either by the operating surgeon or hemophilia physician providing 
postoperative care, blood samples will be drawn for the determination of FVIII activity 
levels. In the event of unexplained, excessive bleeding, the subject will be treated by 
whatever means necessary until adequate hemostasis is achieved. If other rescue 
medications become necessary, the subject will subsequently be withdrawn from this 
BAX 802 surgery study and considered a treatment failure and assigned a GHEA score 
of 0 for remaining assessments (if any). Adverse events and the details of concomitant 
medication and blood product use coincident with the treatment of all unanticipated 
bleeding will be recorded. The use of adjunct antifibrinolytic therapy (such as tranexamic 
acid) is allowed if clinically indicated by the Investigator and/or according to the standard 
of care (SOC) of the subject’s institution.
8.7.3.3.2 Preoperative and Loading Dose
The subject will receive a loading dose calculated according to the formula described in 
Section 8.7.3.3.1 in order to maintain a minimum target FVIII level as required by the 
category and type of surgery. The recommended loading dose will be calculated by the 
Investigator.
The initial loading dose will be administered within 60 to 120 minutes prior to surgery 
(prior to incision/intubation).
The recommended FVIII target level is ≥80% for major surgeries/procedures and ≥50% 
for minor surgeries/procedures.
It is recommended that the surgery starts after FVIII levels have achieved target 
levels. However, if FVIII activity post loading dose is close to the target level, a 
supplemental dose of BAX 802 should be administered without further delaying the 
surgery, based on Investigator’s judgement. Close to the target for major and minor 
surgeries will be defined as levels of ≥ 70% for major and ≥ 40% for minor surgeries, 
respectively. This is 10% from the target, which is considered a normal assay variation.
If FVIII activity post loading dose is not close to the target level, a supplement dose of 
BAX 802 should be administered and surgery delayed until FVIII levels have achieved 
target levels or are in close range.
Subjects will receive subsequent doses of BAX 802 in order to achieve the FVIII target 
levels (see Table 5). All subsequent dosing of BAX 802 should be preceded by 
measurement of residual FVIII levels and dose adjustments must be based on the most 
recent residual FVIII activity levels.
For non-commercial use only

BAX 802
Page 44 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Note: Although peak levels above 200% may be achieved, it is recommended that the 
plasma levels of FVIII are not sustained above 200% of normal.
Note: Dose adjustments should not be based on activated partial thromboplastin time
(aPTT) values.
8.7.3.3.3 Postoperative Dosing
All surgeries/procedures are to have FVIII levels monitored per the diagram in Figure 1:
Figure 1
Postoperative FVIII Monitoring
More frequent monitoring of FVIII activity is advised in subjects who have baseline anti-pFVIII 
inhibitor titers of ≥ 0.6 BU.
All subsequent dosing of BAX 802 must be preceded by measurement of residual FVIII levels pre-dose 
and FVIII level measurement 30 ±5 minutes post-dosing.
Note: It is strongly advised that frequency and/or dose of BAX 802 should be increased in order to 
achieve the recommended FVIII trough levels as per Table 5. The dose of BAX 802 could be 
increased up to 200 U/kg and the frequency of BAX 802 infusions could be increased up to every 
2 hours.
FVIII activity level should be determined immediately after the 
procedure/surgery has been completed, with dose adjustments as 
necessary.
FVIII activity level should also be determined within 4 to 6 hours 
following major or minor surgery, with dose adjustments as 
necessary.
FVIII activity level should be determined at least every 12 hours 
until 48 hours postoperative period (if not discharged yet), with 
dose adjustments as necessary.
Major Surgeries: Beginning on 
postoperative Day 3 (through 
discharge), subjects will have FVIII 
level measurement at least once per 
day in order to assess the adequacy 
of BAX 802 therapy during the 
postoperative period. For 
consistency, it is recommended that 
the daily blood draws are performed 
at the same time of the day, such as 
morning blood draws.
Minor Surgeries: In case the subject 
is hospitalized for more than 24 
hours, daily pre- and post-infusion 
FVIII level determinations as 
described for major surgery have to 
be performed and the dose adjusted 
according to the residual FVIII levels.
For non-commercial use only

BAX 802
Page 45 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
After the initial loading dose, optional re-dosings sufficient to raise FVIII levels to the 
appropriate level as defined for the type of surgery may be administered after a blood 
sample for FVIII determination has been drawn and the required FVIII levels by the local 
laboratory have been determined. 
It is recommended that the FVIII trough levels are within the range targeted for major 
surgery during the treatment period as per Table 5. Dosing adjustments based on aPTT 
values are not allowed.
Note: It is strongly advised that frequency and/or dose of BAX 802 should be increased 
in order to achieve the recommended FVIII trough levels. The dose of BAX 802 could be 
increased up to 200 U/kg (although peak levels above 200% may be achieved, it is 
recommended that the plasma levels of FVIII are not sustained above 200% of normal). 
The frequency of BAX 802 infusions could be increased up to every 2 hours based on the 
investigator’s clinical judgement together with the measured FVIII levels. If expected 
FVIII activity levels are not attained after reasonable repeated high doses of BAX 802
(three [3] repeats recommended), physicians should consider the use of rescue medication
as per Section 10.6.
Any modifications of the FVIII maintenance plan that are deemed necessary during the 
postoperative period will be at the discretion of the Investigator and will be documented 
on the CRFs. 
At a minimum, a blood sample for FVIII determination must be drawn prior to any 
supplemental unscheduled FVIII infusion and 30 ±5 minutes post-dosing.
Note: Since the BAX802 dosing could be as frequent as every 2 hours, getting the pre-
and post-dose FVIII level results in real time might not be operationally feasible for all 
the BAX802 infusions. The sites are recommended to obtain blood samples for both the 
pre- and post-dose FVIII level to permit FVIII measurements for all BAX802 infusions. 
However, in cases where the FVIII activity results are not available because of the time 
of day/night of the frequent infusions, the physicians are not required to wait for all the 
FVIII level results for dose adjustments, but should employ the FVIII assay results when 
available for subsequent dosing, thus utilizing the most recent peak and trough FVIII 
activity levels available together with clinical judgement for dosing decisions.
For non-commercial use only

BAX 802
Page 46 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.7.3.3.4 Dosing for Unrelated/Surgical Site Bleeding Episodes during the 
Postoperative Period
Unrelated bleeding episodes and surgical site bleeding episodes are defined in 
Section 11.2.3. 
The BAX 802 dosing regimen for treatment of these bleeding episodes will be based on 
the guidelines in Table 6. These guidelines may be adjusted by the Investigator based 
upon his or her clinical judgment.
Table 6
BAX 802 Treatment Guidelines for Unrelated/Surgical Site Bleeding Episodes
Type of Bleeding Episode
Recommended 
FVIII Level (%)
BAX 802 Dose
Minor
Early hemarthrosis, mild muscle bleeding, or mild 
oral bleeding, including, epistaxis
20% to 40%
Required dose (U) = [body 
weight (kg) × desired FVIII risea
(U/dL or % of normal)]/
1.2 (U/kg per U/dL)
Titrate subsequent doses to 
maintain recommended FVIII 
trough levels and individual 
clinical response until the 
bleeding resolves.
Moderate
Moderate bleeding into muscles, bleeding into the 
oral cavity, definite hemarthrosis, and known trauma
30% to 60%
Major
Significant gastrointestinal bleeding, intracranial, 
intra-abdominal, or intrathoracic bleeding, central 
nervous system bleeding, bleeding in the 
retropharyngeal or retroperitoneal spaces or iliopsoas 
sheath, fractures, head trauma
60% to 100%
a If the most recent residual FVIII activity level is from the measurement performed ≤4 hours of the 
bleeding episode, use this value to calculate desired FVIII rise. If the most recent residual FVIII activity 
level is from the measurement performed > 4 hours of the bleeding episode, the desired FVIII rise 
should be equivalent to the recommended FVIII level for that type of bleeding episode (as described in 
the column to the left).
Note: It is recommended that the plasma levels of FVIII do not exceed 200% of normal.
It is critical that treatment of a bleed is initiated as soon as possible after occurrence 
of the bleeding episode.
Repeat infusions of BAX 802 can be administered to treat these bleeding episodes, as per 
Investigator’s discretion.
When bleeding is controlled, additional infusions of BAX 802 to maintain hemostasis are 
permitted, if required. Infusions given to treat and control the unrelated bleeding episode 
should be documented in the CRF.
For non-commercial use only

BAX 802
Page 47 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
If the subject cannot continue receiving the IP at the study site, (e.g., because the clinic is 
closed on weekends or subject cannot travel to the site),  follow-up treatment, if any, 
should proceed with SOC products as per Investigator’s discretion.
Note: IP (BAX 802) will not be dispensed to the subjects for in-home use.
For a detailed description of bleeding episodes into different sites see Supplement 20.6.
8.7.4 Thrombosis Prophylaxis and Topical Hemostatics
Commercially available gelatin sponges, topical thrombin, fibrin sealants, absorbable 
collagen preparations or anti-fibrinolytics (e.g., tranexamic acid, ɛ-amino caproic acid) 
may be used according to each institution’s SOC. Details, including the dose, of all 
adjunctive hemostatic medication used will be recorded in the CRFs designed for this 
study and the reason for use given. 
Thrombosis prophylaxis can be administered at the discretion of the Investigator
according to the SOC of each institution and recorded into the respective CRF. 
Thrombosis prophylaxis should preferably consist of mechanical measures such as 
intermittent pneumatic compression (IPC), compression stockings and early mobilization. 
Pharmacologic thrombosis prophylaxis such as low molecular weight heparin (LMWH) 
may be considered for certain surgical interventions such as major orthopedic surgery 
after careful evaluation by the Investigator of the potential risks and benefits.
8.7.5 Investigational Product Accountability
The Investigator will ensure that the IP(s) is stored as specified in the protocol and that 
the storage area is secured, with access limited to authorized study personnel. The 
Investigator will maintain records that the IP(s) was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received and 
disposition. The IP(s) must be dispensed only at the study site or other suitable location 
(e.g., infusion center, as applicable per study design). Records will be maintained that 
includes the subject identification code (SIC), dispensation date, and amount dispensed. 
All remaining partially used and/or unused IP(s) will be returned to the sponsor or 
sponsor’s representative after study completion/termination, or destroyed with the 
permission of the sponsor in accordance with applicable laws and study site procedures.
If IP(s) is to be destroyed, the Investigator will provide documentation in accordance with 
sponsor’s specifications.
For non-commercial use only

BAX 802
Page 48 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.8 Source Data
Per ICH GCP, source data are defined as all information in original records and certified 
copies of original records of clinical findings, observations, or other activities in a clinical 
trial that are necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents (original records or certified copies), which may be in 
paper and/or electronic format. Source data for this study comprise the following: 
hospital records, medical records, clinical and office charts, laboratory notes, memoranda, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical study.
No data will be entered directly onto the case report form (CRF).
For additional information on study documentation and CRFs, see Section 17.2.
For non-commercial use only

BAX 802
Page 49 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subject requires a major or minor elective surgical, dental or other invasive 
procedure
2.
Subject is male and ≥ 12 to ≤ 75 years old at the time of screening
3.
Subject has provided signed informed consent (and assent for adolescent subjects, 
as applicable) in accordance with local regulatory requirements
4.
Subject has severe (FVIII level < 1%) or moderately severe (FVIII level ≤2%) 
CHA with inhibitors to hFVIII of ≥ 0.6 BU, as tested at screening at the central 
laboratory
5.
Subject is not currently receiving or has recently received (< 30 days) ITI therapy
6.
Subject has a Karnofsky performance score of ≥60 at screening
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable 
disease and CD4+ count ≥200 cells/mm3 at screening
8.
Subject 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.
Subject is willing and able to comply with the requirements of the protocol.
9.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
The subject 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-pFVIII inhibitor > 10 BU prior to surgery
5.
Platelet count < 100,000/µL at screening
6.
Subject has another active coagulation disorder, other than hemophilia A, as per the 
medical history
For non-commercial use only

BAX 802
Page 50 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
7.
Planned use of α-interferon with or without ribavarin 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 rpFVIII, or hamster or murine proteins
9.
Subject has an ongoing or recent (within 3 months of screening) thrombo-embolic 
disease, fibrinolysis or disseminated intravascular coagulation (DIC)
10. Subject has been exposed to an IP within 30 days prior to enrollment or is 
scheduled to participate in another clinical study involving an IP or investigational 
device during the course of this study
11. Subject is unable to tolerate quantity of blood to be drawn for protocol procedures
12. Subject is a family member or employee of the Investigator. 
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw (i.e., reduce the degree of participation in the 
study) consent for continued participation and data collection. The reason for withdrawal 
will be recorded on the End of Study CRF. Assessments to be performed at the
termination visit (including in cases of withdraw or discontinuation) are described in 
Section 10.7, Section 20.3, and Section 20.4.
Discontinuation (ie, complete withdrawal from study participation) may be due to 
dropout (i.e., active discontinuation by subject) or loss to follow-up (i.e., discontinuation 
by subject without notice or action). Additionally, the Investigator and sponsor have the 
discretion to discontinue any subject from the study if, in their judgment, continued 
participation would pose an unacceptable risk for the subject.
Subjects also will be withdrawn from treatment or discontinued from further study 
participation for the following reasons:

AEs/SAEs that in the Investigator’s or sponsor’s opinion, poses an unacceptable 
risk for continued dosing in the subject

Participation in another clinical study involving an IP during the course of the study

The subject experiences a severe anaphylactic reaction

The subject had uncontrolled hemorrhage that was the result of inadequate 
therapeutic response despite proper dosing of BAX 802, necessitating rescue 
therapy with bypassing agents.
For non-commercial use only

BAX 802
Page 51 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10. STUDY PROCEDURES
10.1 Informed Consent
Any patient who provides informed consent or assent, as applicable (i.e., signs and dates 
the informed consent form (ICF) and assent form, if applicable) is considered a subject in 
the study.
10.2 Subject Identification Code
The following series of numbers will comprise the SIC: protocol identifier (241502) to be 
provided by the sponsor, 3-digit number study site number (e.g., 002) to be provided by 
the sponsor, and 3-digit subject number (e.g., 003) reflecting the order of providing
informed consent. For example, the third subject who signed an ICF at study site 002 will 
be identified as Subject 241502-002003. All study documents (e.g., CRFs, clinical 
documentation, sample containers, drug accountability logs, etc.) will be identified with 
the SIC. Additionally, a uniquely coded SIC(s) is permitted as long as it does not contain 
a combination of information that allows identification of a subject (e.g., collection of a 
subject’s initials and birth date would not be permitted), in compliance with laws 
governing data privacy.
10.3 Screening and Study Visits
The study site is responsible for maintaining a screening log that includes all subjects 
who provided informed consent. The log also will serve to document the reason for 
screening failure.
All screening data will be collected and reported in CRFs, regardless of screening 
outcome. If a subject is re-screened, the End of Study CRF should be completed, and a 
new ICF, new SIC and new CRF are required for that subject. 
Subjects who fail screening due to a single laboratory test result that does not meet 
eligibility criteria may have that laboratory test repeated at the discretion of the 
Investigator. This will include a repeat of only the failed assessment; complete re-
screening will not be necessary. In these cases, a new SIC is not required; the subject will 
maintain their original SIC. The repeat of a screening assessment is allowed once. A 
repeat assessment must take place within 42 days of the initial screening for any subject 
requiring repeat of a screening assessment. If this timeframe is exceeded, then all 
screening assessments must be repeated and the subject assigned a new SIC. Exemptions 
are possible for administrative reasons and have to be approved by the sponsor. Subjects 
with an inadequate interval between screening and prior IP drug (other than BAX 802) 
administration or prior participation in a drug or device study (i.e., 30 days), may be 
re-screened only once and only when the required interval is reached. 
For non-commercial use only

BAX 802
Page 52 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The screening assessment should be performed within 45 days prior to the planned 
elective surgery.
The overall study design is illustrated in Supplement Figure 2. Details on the procedures 
to be performed at each study visit, including screening, can be found in Supplement 20.3
and Supplement 20.4.
10.4 Study Periods
The study will be divided into 5 periods: 
1.
Screening
2.
Preoperative 
3.
Intraoperative
4.
Postoperative
5.
End of study 
A detailed description of study procedures per study period is provided in 
Supplement 20.1.
10.4.1 GHEA3 Visit
This visit will be performed at discharge or within 24 to 72 hours after the last 
perioperative treatment dose of BAX 802 (whichever is earlier). Study procedures will be 
performed as per Table 9 and blood samples will be collected as per Table 10.
Sites must make every effort to complete 3 independent GHEA assessments (GHEA1, 
GHEA2, GHEA3) for both minor and major procedures, preferably allowing for as much 
time as possible to pass between assessments within the windows specified in this 
protocol. In cases such as minor surgeries/procedures, there might be a possibility that the 
subject is discharged < 24 hours following the surgery/procedure but continues receiving 
BAX 802 in hospital (e.g., day hospital) setting. In these cases, the GHEA2 hemostatic 
efficacy assessment should be performed the following day. Also, the GHEA3 Visit 
should be performed within 24 to 72 hours after the last perioperative treatment dose of 
BAX 802. Both GHEA2 and GHEA3 assessments can be performed on the day after the 
surgery/procedure if the subject does not need any further BAX 802 administration for 
perioperative management.
For non-commercial use only

BAX 802
Page 53 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.4.2 Antibody Testing Visit
A visit will be performed between 7 to 14 days after last perioperative dose of BAX 802. 
Study procedures will be performed as per Table 9 and blood samples will be collected 
for antibody testing and other tests as per Table 10.
10.4.3 Unscheduled Visit
An unscheduled visit could be performed for events such as antibody testing or 
management of bleeding episodes.
10.4.4 End of Study Visit
The End of Study Visit will be performed 42 ± 7 days after last perioperative dose of 
BAX 802.
Note: The End of Study Visit should be performed in ALL subjects who have received at 
least one dose of BAX 802 during Study 241502. This applies also to subjects who 
receive dose(s) of BAX 802 and do not undergo surgery and withdraw from the study 
AND to subjects who receive any rescue medications and subsequently withdraw from 
the study.
10.5 Medications and Non-Drug Therapies 
The following medications are not permitted anytime during perioperative period until 
the last GHEA assessment (GHEA3) has been performed (unless used as rescue 
medications or used to treat unrelated/surgical site bleeding episodes as specified below):
Medications:

Hemophilia inhibitor bypassing therapy (recombinant factor VIIa [NovoSeven] 
within 3 hours or activated prothrombin complex concentrate [aPCC; FEIBA]) 
within 12 hours prior to initial BAX 802 administration) unless used as a rescue 
medication (Section 10.6) after failure/study withdrawal or used to treat 
unrelated/surgical site bleeding episodes (Section 11.2.3).

Hemophilia medication other than BAX 802. 
A subject who has taken any of these medications will be considered a protocol deviation.
The following medications and non-drug therapies are permitted within 30 days before 
study entry and during the course of the study:
For non-commercial use only

BAX 802
Page 54 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Medications:

The management of a serious thrombo-embolic event may require anticoagulant 
medication and this may need to be administered concurrent with the use of 
BAX 802 to ensure that a re-bleed or continuing severe hemorrhage does not occur 
on withdrawal of BAX 802 (see Section 10.6). In such instances the Sponsor’s 
medical monitor should be consulted.

Any medications deemed necessary by the subject’s physician to treat or prevent 
any medical condition (with the exception of those listed as not permitted)

Any over-the-counter medication used by the subject to treat symptoms or signs of 
any medical condition

Supplemental vitamins and minerals
Non-drug therapies:

Any non-drug therapy (e.g., physiotherapy) deemed necessary by the subject’s 
physician to treat or prevent any medical condition
10.6 Rescue Medications
Bypassing agents (FEIBA or NovoSeven) can be used as a rescue medication if expected 
plasma FVIII activity levels are not attained or if bleeding is not controlled despite proper 
dosing of BAX 802 during the intra- or postoperative period of the study. Note: It is 
strongly advised that frequency and/or dose of BAX 802 should be increased in order to 
achieve the recommended FVIII trough levels. The dose of BAX 802 could be increased 
up to 200 U/kg (although peak levels above 200% may be achieved, it is recommended 
that the plasma levels of FVIII are not sustained above 200% of normal). The frequency 
of BAX 802 infusions could be increased up to every 2 hours based on the investigator’s 
clinical judgement together with the measured FVIII levels. If expected FVIII activity 
levels are not attained after reasonable repeated high doses of BAX 802 (three [3] repeats 
recommended), physicians should consider the use of rescue medication.
Patients switched to rescue medication are required to come to the End of study Visit 42 
± 7 days following the last perioperative dose of BAX 802.
For non-commercial use only

BAX 802
Page 55 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.7 Subject Completion/Discontinuation
A subject is considered to have completed the study when he ceases active participation 
in the study because the subject has, or is presumed to have, completed all study
procedures according with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation CRF, including: completed, screen failure, AE (e.g., death), 
discontinuation by subject (e.g., lost to follow-up [defined as 3 documented unsuccessful 
attempts to contact the subject], and dropout), physician decision (e.g., progressive 
disease, non-compliance with IP/protocol violation(s), recovery), study terminated by 
sponsor, or other (reason to be specified by the Investigator, e.g., technical problems). 
Regardless of the reason, all data available for the subject up to the time of 
completion/discontinuation should be recorded on the appropriate CRF.
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit preferably 42 ± 7 days following the last perioperative dose 
of BAX802. If the completion/termination visit is done as an additional, unscheduled 
visit, the assessment results shall be recorded with the completion/termination visit. If a 
subject terminates participation in the study and does not return for the
completion/termination visit, their last recorded assessments shall remain recorded with 
their last visit. The reason for discontinuation will be recorded, and the data collected up 
to the time of discontinuation will be used in the analysis and included in the clinical 
study report. If additional assessments are required, the assessments shall be recorded 
separately. Assessments to be performed at the termination visit (including in cases of
withdraw or discontinuation) can be found in Supplement 20.3 and Supplement 20.4.
In the event of subject discontinuation due to an AE, clinical and/or laboratory 
investigations that are beyond the scope of the required study observations/assessments 
may be performed as part of the evaluation of the event. These investigations will take 
place under the direction of the Investigator in consultation with the sponsor, and the 
details of the outcome may be reported to the appropriate regulatory authorities by the 
sponsor.
For non-commercial use only

BAX 802
Page 56 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
10.8 Procedures for Monitoring Subject Compliance
Subject compliance with the procedures and treatment(s) outlined above will be 
monitored by direct review of the subject’s source data at the sites and evaluated against 
the protocol requirements. Additionally, electronic edit checks will be performed on all 
protocol-specified procedures and treatment data that are collected to ensure quality and 
accuracy. Deviations from the protocol-specified procedures and treatments will be noted 
in the final study report.
All study procedures are to be performed under the direct supervision of the 
Investigator/a licensed healthcare professional at the study site, and thus, no separate 
procedures will be used to monitor subject compliance.
For non-commercial use only

BAX 802
Page 57 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11. ASSESSMENT OF EFFICACY
11.1 Primary Efficacy Endpoint: Global Hemostatic Efficacy Assessment Score
The primary outcome measure is the proportion of all surgical or other invasive 
procedures with a “good” or “excellent” response measured by GHEA. The GHEA score
is composed of 3 individual categorical ratings (GHEA1, GHEA2, GHEA3) which will 
be added together to form the total GHEA score according to Table 1 (see Section 8.4.1).
11.2 Secondary Efficacy Endpoints
11.2.1 Blood Loss
The observed versus predicted (recorded prior to surgery) operative blood loss will be 
described for the period from initiation of the intervention to discharge or 24 to 72 hours
after the last perioperative treatment dose of BAX 802 (whichever is first), as applicable.
Prior to the surgery, the surgeon/Investigator will predict the estimated volume (in mL) of 
the expected average and maximum blood loss for the planned surgical intervention in a 
hemostatically normal individual of the same sex, age, and stature as the study subject, 
for intraoperative, postoperative, and overall perioperative time periods. Every effort 
should be made to predict the volume as precisely as possible, also taking into account, 
for example, the use of a tourniquet or placement of a postoperative drain and whether or 
not suction is used. The estimate will be for the intraoperative time period and from 
completion of the procedure until approximately 24 hours post-surgery and for the overall 
perioperative time period (assessed at discharge or 24 to 72 hours after the last 
perioperative treatment dose of BAX 802). The expected normal/average, and maximal 
blood loss and transfusion requirement estimate will be timestamped into the source 
documentation and/or blood loss form prior to the surgery, and then transferred into the 
CRF. No changes will be allowed to these estimates after the surgery.
The intraoperative blood loss will be measured by determining the volume of blood and 
fluid removal through suction into the collection container (waste box and/or cell saver) 
and the estimated blood loss into swabs and towels during the procedure, per the 
anesthesiologist’s record. 
Postoperatively, blood loss will be determined by the drainage volume collected, which 
will mainly consist of drainage fluid via vacuum or gravity drain, as applicable. In cases 
where no drain is present, blood loss will be determined by the surgeon’s clinical 
judgment, as applicable or entered as “not available”.
For non-commercial use only

BAX 802
Page 58 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.2.2 Blood Transfusions
The type and volume (in mL) of blood products (e.g., whole blood, red blood cells, 
platelets and plasma) will be recorded from initiation of the intervention to discharge or 
24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier). 
Furthermore, also salvage of blood obtained from autologous transfusion systems, (e.g., 
cell savers) will be recorded. In addition, the type and volume of fluid replacement and 
volume expanders will be recorded as concomitant medication (e.g., volume of salvaged 
blood, red blood cells, platelets and other blood products transfused).
11.2.3 Bleeding Episodes
 
 
 
, until the time of discharge or until the subject resumes his previous 
treatment regimen, whichever is later. 
Any subject who is deemed to have excessive, unexplained bleeding will have blood 
drawn for measurement of FVIII levels.
Bleeding episodes will be classified as follows:

Unrelated bleeding episodes: an unrelated bleeding episode is defined as any 
bleeding occurring at a different anatomical site than the surgery site during the 
postoperative period. 

Surgical site bleeding episodes: Surgical site bleeding episodes are any bleeding at 
the surgical/procedure site which occurs after the GHEA3 assessment has been 
performed.
These bleeding episodes will be treated as follows:

If these unrelated bleeding episodes or surgical site bleeding episodes occur during 
the subject’s stay in hospital, it is recommended that subjects are treated with 
BAX 802. BAX 802 will be dosed as per the most recent residual FVIII activity 
level and clinical judgment using the dosing regimen provided in Table 6
[Required dose = body weight (kg) × desired FVIII rise (U/dL or % of normal)]/
1.2 (U/kg per U/dL)]. All subsequent dosing of BAX 802 should be preceded by 
measurement of residual FVIII levels and dose adjustments must be based on the 
most recent residual FVIII activity levels.
For non-commercial use only

BAX 802
Page 59 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

If these unrelated bleeding episodes or surgical site bleeding episodes occur after 
the subject has been discharged, subjects may be treated with BAX 802 or SOC, as 
per Investigator's discretion. Note: IP (BAX 802) will not be dispensed to the 
subjects for in-home use.
An unscheduled visit could be performed for the management of bleeding episodes.
11.2.4 BAX 802 Administration
The daily and total weight-adjusted administration of BAX 802 per subject will be 
recorded.
11.2.5 Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical Site
Bleeding Episodes
An unrelated bleeding episode is defined as any bleeding occurring at a different 
anatomical site than the surgery site during the postoperative period. Surgical site 
bleeding episodes are any bleeding at the surgical/procedure site which occurs after the 
GHEA3 assessment has been performed. These bleeding episodes will be treated as per 
Section 11.2.3.
If subject is treated with BAX 802 for unrelated bleeding episodes or surgical site 
bleeding episodes, the subject will rate the severity (minor, moderate, or major) of the 
bleeding episode and will rate the overall treatment response at 24 ±2 hours after the 
initiation of treatment and at the resolution of bleed (if not resolved within 24 hours) 
using a 4-point efficacy rating scale (Table 7). Since the efficacy rating is based to a large 
degree on cessation of pain, the Investigator/subject shall, particularly in the event of 
injury-related bleeding into ≥1 location, consider the injury-related symptoms when 
performing the efficacy rating 24 hours after initiating treatment and at resolution of 
bleed. Data should be collected as an unscheduled visit.
As per Table 5, multiple infusions of BAX 802 may be administered for the treatment of 
a bleeding episode. The overall response to all infusions combined is the rating that will 
be recorded at resolution of bleed.
For non-commercial use only

BAX 802
Page 60 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 7
Efficacy Rating Scale for Treatment of Unrelated/Surgical Site Bleeding Episodes
Excellent
Full relief of pain and/or cessation of objective signs of bleeding (e.g., swelling, 
tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) 
after a single infusion. No additional infusion is required for the control of bleeding. 
Administration of further infusions to maintain hemostasis would not affect this scoring.
Good
Definite pain relief and/or improvement in signs of bleeding after a single infusion. 
Possibly requires more than 1 infusion for complete resolution.
Fair
Probable and/or slight relief of pain and slight improvement in signs of bleeding after a 
single infusion. Required more than 1 infusion for complete resolution.
None
No improvement or condition worsens.
As per Table 5, multiple infusions of BAX 802 may be administered for the treatment of 
a bleeding episode. The overall response to all infusions combined is the rating that will 
be recorded at resolution of bleed.
11.3 Factor VIII Activity
Blood will be obtained for assessment of FVIII activity at screening (tests to be 
performed at the central laboratory). Results from local laboratory will be used to 
make any dosing decisions.
Blood will be obtained for assessment of FVIII activity for patient management purposes 
at the following time points (tests to be performed at the local laboratory, with 
additional back-up samples to be tested in 1 batch at the central laboratory):

Within 30 minutes prior to the administration of the initial loading dose 
preoperatively and 30 ±5 minutes post-infusion. If re-dosing with BAX 802 is 
required to obtain the required FVIII levels, an additional blood sample needs to 
be drawn 30 ±5 minutes following the re-dosing with BAX 802.

Postoperatively until the GHEA3 visit: daily within 30 minutes prior to the infusion 
of BAX 802 and 30 ±5 minutes post-infusion. 
Pre- and post-dosing blood draws for FVIII activity level determination should 
also be performed for each BAX 802 administration.

FVIII activity will also be assessed if the subject has excessive, unexplained 
bleeding at any time intra-or postoperatively, or whenever deemed necessary 
according to the institution’s SOC.
For non-commercial use only

BAX 802
Page 61 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11.3.1 Blood Sampling and Processing for FVIII Analysis
At each blood sampling time point whole blood will be collected in blood sampling tubes 
will be collected in S-Monovette® tubes (Sarstedt, Nümbrecht, Germany) containing 
3.2% trisodium citrate, or equivalent blood drawing equipment (e.g., Vacutainer tubes), 
and immediately mixed. The citrated whole blood samples will be capped and transported 
at room temperature (i.e., 20 to 25°C) to the local clinical laboratory for centrifugation, 
processing, and storage. Monovettes must be kept in an upright position at all times to 
avoid leakage.
All samples taken through 6 hours post-dosing will be collected from an extremity other 
than that used for the infusion of study product. Thereafter, either extremity may be used 
to obtain samples.
If the subject has a central venous catheter, the central line should be used to administer 
the infusion and a peripheral venipuncture should be used to collect the blood samples. 
In the event that a blood sample must be drawn through the central line used for 
administration of IP, the line must first be flushed with 5 mL normal saline or other 
suitable catheter flush solution that does not contain anticoagulant. At least 5 mL of 
whole blood must be collected and discarded prior to obtaining the sample. 
All citrated plasma samples will be stored and shipped to the central laboratory at 
≤-70°C for testing. 
All back-up samples collected during the perioperative period will be shipped to the 
central laboratory as soon as possible in 1 batch and analyzed, as needed. 
Blood samples will be analyzed for FVIII activity (1-stage clotting assay and the 
chromogenic assay) at the central laboratory. The 1-stage FVIII activity assay will serve 
as the primary assay; the chromogenic assay of FVIII activity will be used to provide
supportive data. Local laboratories are expected to use a 1-stage clotting assay.
For non-commercial use only

BAX 802
Page 62 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12. ASSESSMENT OF SAFETY
12.1 Adverse Events
12.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP 
that does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom (e.g., rash, pain, discomfort, fever, dizziness, etc.), disease (e.g., peritonitis, 
bacteremia, etc.), or outcome of death temporally associated with the use of an IP, 
whether or not considered causally related to the IP.
12.1.1.1 Serious Adverse Event
An SAE is defined as an untoward medical occurrence that at any dose meets 1 or more 
of the following criteria:

Outcome is fatal/results in death (including fetal death)

Is life-threatening – defined as an event in which the subject was, in the judgment 
of the Investigator, at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death had it been more severe.

Requires inpatient hospitalization or results in prolongation of an existing 
hospitalization – inpatient hospitalization refers to any inpatient admission, 
regardless of length of stay.

Results in persistent or significant disability/incapacity (i.e., a substantial disruption 
of a person’s ability to conduct normal life functions)

Is a congenital anomaly/birth defect

Is a medically important event – a medical event that may not be immediately
life-threatening or result in death or require hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the definitions above. Examples of such events are:

Intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependence or drug abuse.

Reviewed and confirmed seroconversion for HIV, hepatitis A virus (HAV), 
hepatitis B virus (HBV), HCV, hepatitis E virus (HEV), or parvovirus B19 
(B19V).
For non-commercial use only

BAX 802
Page 63 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

Thrombo-embolic events (e.g., stroke, myocardial infarction, deep vein 
thrombosis, pulmonary embolism).

The confirmed development of de-novo anti-pFVIII inhibitory antibodies or 
increases of > 10 BU in pre-existing titers of anti-pFVIII inhibitory antibodies 
(see Section 12.1.1.1.1)
Planned hospitalization for any study procedures as per the protocol will not be 
considered as an SAE.
12.1.1.1.1 Inhibitory Serious Adverse Events
The development of de-novo anti-pFVIII inhibitory antibodies (≥0.6 BU) must be 
confirmed with a second blood draw 7 to 14 days after the initial confirmed positive de 
novo result (or repeat testing of original sample if a second draw is not possible). 
Confirmation of de novo inhibitory antibodies or a confirmed increase of > 10 BU in 
pre-existing titers of anti-pFVIII inhibitory antibodies must be reported as a SAE within 
24 hours, and followed up.
Increases in pre-existing titers of anti-pFVIII inhibitory antibodies will require a second 
confirmatory test 7 to 14 days after the initial confirmed positive increase (or repeat 
testing of original sample if a second draw is not possible). If the protocol-defined 
significant increase (> 10 BU) is confirmed, it will be reported as an SAE.
Safety will be further monitored by the Investigator and medical monitor to evaluate the 
clinical significance of the inhibitor level. Although the development of, or increase in, 
anti-pFVIII inhibitory antibody titers may not necessarily indicate a failure of response to 
BAX 802, the inhibitor levels and patient response will be closely monitored and an 
alternative therapy will be considered for lack of efficacy, if applicable.
12.1.1.2 Suspected Unexpected Serious Adverse Reaction
Any suspected adverse reaction to study treatment that is both serious and unexpected. 
The event(s) must meet all of the following:

Suspected adverse reaction

Serious

Unexpected

Assessed as related to study treatment
For non-commercial use only

BAX 802
Page 64 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Once determined to meet the criteria for a SUSAR, an SAE should be submitted to 
regulatory agencies expeditiously.
12.1.1.3 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.4 Unexpected Adverse Events
An unexpected AE is an AE whose nature, severity, specificity, or outcome is not 
consistent with the term, representation, or description used in the Reference Safety 
Information (RSI). “Unexpected” also refers to the AEs that are mentioned in the IB as 
occurring with a class of drugs or as anticipated from the pharmacological properties of 
the product, but are not specifically mentioned as occurring with the particular product 
under investigation. The expectedness of AEs will be determined by the sponsor using 
the Company Core Data Sheet for OBIZUR as the RSI. This determination will include 
considerations such as the number of AEs previously observed, but not on the basis of 
what might be anticipated from the pharmacological properties of a product.
12.1.1.5 Preexisting Diseases
Preexisting diseases that are present before entry in to the study are described in the 
medical history, and those that manifest with the same severity, frequency, or duration 
after IP exposure, will not be recorded as AEs. However, when there is an increase in the 
severity, duration, or frequency of a preexisting disease, the event must be described on 
the AE CRF.
12.1.2 Assessment of Adverse Events
For the purposes of this study, the following non-serious events experienced after the first 
IP exposure are collected under other study endpoints and thus are not reportable on the 
AE CRF, nor will they be included in the analysis of AEs:
Bleeding episodes are part of the underlying disease and therefore are not AEs; they will 
be assessed as part of the efficacy assessments. However, the Investigator may decide 
that the event is an AE if the event also would have occurred in a normal patient under 
the same circumstances. If a bleeding episode was caused by an injury, the injury will be 
reported as an AE. All bleeding episodes must be entered in the bleeding event CRF.
For non-commercial use only

BAX 802
Page 65 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
All other/Each AE from the first IP exposure until study completion or discontinuation 
date will be described on the AE CRF using the medical diagnosis (preferred), or, if no 
diagnosis could be established at the time of reporting the AE, a symptom or sign, in 
standard medical terminology in order to avoid the use of vague, ambiguous, or 
colloquial expressions (see definition in Section 12.1). Each AE will be evaluated by the 
Investigator for:

Seriousness as defined in Section 12.1.1.1

Severity as defined in Section 12.1.2.1

Causal relationship to IP exposure or study procedure as defined in Section 12.1.2.2
For each AE, the outcome (i.e., recovering/resolving, recovered/resolved, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, or unknown) and if 
applicable action taken (i.e., dose increased, dose not changed, dose reduced, drug 
interrupted, drug withdrawn, not applicable, or unknown) will also be recorded on the AE 
CRF. Recovering/resolving AEs will be followed until resolution, medically stabilized, or
30 days after the study completion/termination visit, whichever comes first. If the 
severity rating for an ongoing AE changes before the event resolves, the original AE 
report will be revised (i.e., the event will not be reported as separate AE). During the 
course of any AE, the highest severity rating will be reported.
Deviations from the protocol-specified dosage (including overdosing, underdosing, 
abuse, and withdrawal), treatment errors (including incorrect route of administration, use 
of an incorrect product, and deviations from the protocol-defined dosing schedule), 
failures of expected pharmacological actions, and unexpected therapeutic or clinical 
benefits will be followed with regard to occurrence of AEs, lack of efficacy, and/or other 
observations because these events may be reportable to regulatory authorities.
If an Investigator becomes aware of an SAE occurring in a subject after study 
completion, the SAE must be reported on the provided SAE Report Form within 24 hours 
after awareness; no additional reporting on CRFs is necessary.
For non-commercial use only

BAX 802
Page 66 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.1.2.1 Severity
The Investigator will assess the severity of each AE using his/her clinical expertise and 
judgment based on the most appropriate description below:

Mild

The AE is a transient discomfort and does not interfere in a significant manner
with the subject’s normal functioning level.

The AE resolves spontaneously or may require minimal therapeutic 
intervention.

Moderate

The AE produces limited impairment of function and may require therapeutic 
intervention.

The AE produces no sequela/sequelae.

Severe

The AE results in a marked impairment of function and may lead to temporary 
inability to resume usual life pattern.

The AE produces sequela/sequelae, which require (prolonged) therapeutic 
intervention.
These severity definitions will also be used to assess the severity of an AE with a 
study-related procedure(s), if necessary.
12.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, for 
example, assessment of temporal relationships, dechallenge/rechallenge information, 
association (or lack of association) with underlying disease, presence (or absence) of a 
more likely cause, and physiological plausibility. For each AE, the Investigator will 
assess the causal relationship between the IP and the AE using his/her clinical expertise 
and judgment according to the following most appropriate algorithm for the 
circumstances of the AE:
Not related (both circumstances must be met)
Is due to underlying or concurrent illness, complications, concurrent 
treatments, or effects of concurrent drugs
For non-commercial use only

BAX 802
Page 67 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Is not associated with the IP (i.e., does not follow a reasonable temporal 
relationship to the administration of IP or has a much more likely alternative 
etiology).
Unlikely related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists
Possibly related (both circumstances must be met)
Follows a reasonable temporal relationship to the administration of IP
An alternative etiology is equally or less likely compared to the potential 
relationship to the IP
Probably related (both circumstances must be met)
Follows a strong temporal relationship to the administration of IP, which may 
include but is not limited to the following:
o
Reappearance of a similar reaction upon re-administration (positive 
rechallenge)
o
Positive results in a drug sensitivity test (skin test, etc.)
o
Toxic level of the IP as evidenced by measurement of the IP 
concentrations in the blood or other bodily fluid
Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related, the Investigator shall provide the 
alternative etiology. These causality definitions will also be used to assess the 
relationship of an AE with a study-related procedure(s), if necessary.
12.1.2.3 Safety Reporting
Adverse events/SAEs will be assessed at all study visits as outlined in the Schedule of 
Study Procedures and Assessments (see Table 9) and Section 12.1.
Adverse Events/SAEs are to be recorded on the AE page of the CRF. Each event should 
be recorded separately.
Any SAE, including death due to any cause, which occurs during this study, 
whether or not related to the IP, must be reported immediately (within 24 hours 
of the study center’s first knowledge of the event). 
For non-commercial use only

BAX 802
Page 68 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Any SAEs must be reported using the paper SAE Report Form to meet the 24 hour 
timeline requirement (for contacts and instructions refer to the SAE Report Form).
The initial SAE information reported on the applicable SAE Report Form must at least 
include the following:

Protocol number

Subject identification number and demographics (gender, age at onset of event 
and/or date of birth)

IP exposure

Medical Term for Event (Diagnosis preferably)

Description of the (S)AE, including:

Date of onset

(S)AE treatment (drug, dose, route of administration)

Causal relationship by the Investigator

Measures taken (i.e., action taken regarding IP in direct relationship to the AE)

Seriousness criteria (i.e., death, life-threatening, or other criterion)

Cause of death

Autopsy findings (if available)

Name, address, fax number, email, and telephone number of the reporting

Investigator
12.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the 
protocol, in order to protect subjects participating in a clinical trial from immediate harm. 
Urgent safety measures may be taken by the sponsor or clinical Investigator, and may 
include any of the following:
Immediate change in study design or study procedures
Temporary or permanent halt of a given clinical trial or trials
Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety
For non-commercial use only

BAX 802
Page 69 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The Investigator may take appropriate urgent safety measures in order to protect subjects 
against any immediate hazard to their health or safety. The measures should be taken 
immediately and may be taken without prior authorization from the sponsor. In the 
event(s) of an apparent immediate hazard to the subject, the Investigator will notify the 
sponsor immediately by phone and confirm notification to the sponsor in writing as soon 
as possible, but within 1 calendar day after the change is implemented. The sponsor will 
also ensure the responsible ethics committee (ECs) and relevant competent authority(s) 
are notified of the urgent safety measures in such cases according to local regulations.
12.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to IP are not 
considered AEs (according to the definition of AE, see Section 12.1). However, each 
serious untoward medical occurrence experienced before the first IP exposure (i.e., from 
the time of signed informed consent up to but not including the first IP exposure) will be 
described on the AE CRF (and SAE Report Form if CRF is not available). These events 
will not be considered as SAEs and will not be included in the analysis of SAEs.
For the purposes of this study, each of the following non-serious events experienced after 
the first exposure to IP will not be considered an AE, and thus, not included in the 
analysis of AEs:

Bleeding episodes are part of the underlying disease and therefore are not AEs; they 
will be assessed as part of the efficacy assessments. If a bleeding episode was 
caused by an injury, the injury would not be reported as an AE, unless it resulted in 
a medical finding other than a bleeding episode (e.g., abrasion of skin). Therefore, 
any hemophilia-related event (e.g., hemarthrosis [presenting as swelling, pain, and 
decreased range of motion], bruising, hemorrhages, or pain at bleeding episode site) 
will not be reported as AEs. However, the Investigator may decide that the event is 
an AE if the event also would have occurred in a normal patient under the same 
circumstances.
12.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to 
identity, quality, durability, reliability, safety and performance of the product but did not 
result in an AE. The NMCs include but are not limited to the following:

A failure of a product to exhibit its expected pharmacological activity and/or design 
function, e.g., reconstitution difficulty

Missing components
For non-commercial use only

BAX 802
Page 70 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL

Damage to the product or unit carton

A mislabeled product (e.g., potential counterfeiting/tampering)

A bacteriological, chemical, or physical change or deterioration of the product 
causing it to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the 
sponsor within 1 business day. If requested, defective product(s) will be returned to the 
sponsor for inspection and analysis according to procedures.
12.5 Medical, Medication, and Non-Drug Therapy History
At screening, the subject’s medical history will be described for the following body 
systems including severity (defined in Section 12.1.2.1) or surgery and start and end 
dates, if known: eyes, ears, nose, and throat; respiratory; cardiovascular; gastrointestinal; 
musculoskeletal; neurological; endocrine; hematopoietic/lymphatic; dermatological; and 
genitourinary.
Medical history will include the collection of hemophilia history, bleeding episode 
history, and history of aPCC or rFVIIA usage for 6 months prior to screening. Relevant 
medical and surgical history and all medications taken 3 months prior to screening will 
also be collected.
All medications taken and non-drug therapies received within 3 months before providing 
informed consent until completion/termination will be recorded on the concomitant 
medications and non-drug therapies CRFs.
12.6 Physical Examinations
At screening and subsequent study visits (as described in Table 9), a physical 
examination will be performed on the following body systems: general appearance, head 
and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and 
joints, lymph nodes, skin, and neurological. At screening, if an abnormal condition is 
detected, the condition will be described on the medical history CRF. At study visits, if a 
new abnormal or worsened abnormal pre-existing condition is detected, the condition will 
be described on the AE CRF. If the abnormal value was not deemed an AE because it 
was due to an error, due to a preexisting disease (described in Section 12.1.1.5), not 
clinically significant, a symptom of a new/worsened condition already recorded as an AE, 
or due to another issue that will be specified, the Investigator will record the justification 
on the source record.
For non-commercial use only

BAX 802
Page 71 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.7 Clinical Laboratory Parameters
Clinical chemistry and hematology assessments will be performed on whole blood and 
EDTA-anticoagulated serum, respectively, at the central laboratory. Details of blood 
sampling volumes are presented in the laboratory manual and master ICF.
12.7.1 Hematology, Clinical Chemistry, and Urinalysis
The hematology panel will consist of complete blood count (hemoglobin, HCT, 
erythrocytes [i.e., red blood cell count], and leukocytes [i.e., white blood cell count]) with 
differential (i.e., basophils, eosinophils, lymphocytes, monocytes, neutrophils) and 
platelet counts.
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, 
creatinine, and glucose.
The frequency of blood draws for clinical and hematology assessments is provided in 
Table 10. 
The urinalysis panel will consist of pH, protein, ketones, glucose, bilirubin, blood, 
urobilinogen, specific gravity by dipstick and microscopy if any findings are abnormal.
Urine will be obtained for assessment of urinalysis parameters as per Table 10.
12.7.2 Viral Serology
Viral serology testing will include HIV-1 and HIV-2 antibody, HAV (immunoglobulin M 
[IgM] and total antibodies), hepatitis B surface antigen (HBsAg), hepatitis B surface 
antibody (HBsAb), hepatitis B core antibody (HBcAb), HCV antibody, and parvovirus 
B19 (IgM and immunoglobulin G [IgG] antibodies). The HIV and HCV titer will be 
confirmed by PCR for all subjects reported as HIV and HCV positive. All viral serology 
assessments will be performed at screening. Any positive HBsAg test will be repeated 
using a new blood sample.
12.7.3 Immunogenicity
Immunogenicity assessments will include anti-pFVIII and hFVIII binding (IgG and IgM) 
and inhibitory antibodies and anti-BHK binding antibodies.
Blood samples will be collected for the assay of anti-pFVIII and hFVIII binding and 
inhibitory antibodies and anti-BHK binding antibodies at the times indicated in Table 9
and Table 10.
For non-commercial use only

BAX 802
Page 72 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
All FVIII assays related to study subject management decisions by the Investigator will 
be performed at the Investigator’s local laboratory.
A central reference laboratory will perform assays (anti-pFVIII, anti-hFVIII, and 
anti-BHK) on samples taken at the times indicated in Table 9 and Table 10.
Binding antibodies to human and porcine FVIII (both IgG and IgM) and binding 
antibodies to BHK proteins will be analyzed using validated enzyme-linked 
immunosorbent assays (ELISAs) using a multi-tiered approach consisting of screening 
assay, titer determination and confirmation of specificity. 
 
 
 
The assessment of inhibitory antibodies to pFVIII and hFVIII will be determined using a 
Bethesda assay (with the Nijmegen modification if possible). Further details on blood 
collection, tube preparation and shipment will be provided in the Laboratory Manual.
12.7.4 Assessment of Laboratory Values
12.7.4.1 Assessment of Abnormal Laboratory Values
The Investigator’s assessment of each laboratory value will be recorded on the CRF. For 
each abnormal laboratory value, the Investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the Investigator
will indicate if the value constitutes a new AE (see definition in Section 12.1, and record
the sign, symptom, or medical diagnosis on the AE CRF), is a symptom or related to a
previously recorded AE, is due to a pre-existing disease (described in Section 12.1.1.5), 
or is due to another issue that will be specified. If the abnormal value was not clinically
significant, the Investigator will indicate the reason, i.e., because it is due to a preexisting 
disease, due to a laboratory error, or due to another issue that will be specified.
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically
indicated. Any abnormal value that persists should be followed at the discretion of the 
Investigator.
12.7.5 Backup Samples and Biobanking
Backup samples taken and stored short-term may be used for re-testing, follow-up of an 
AE(s) or other test results (such as FVIII activity and antibody testing), and/or assay 
development.
For non-commercial use only

BAX 802
Page 73 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
After study testing is completed, the remaining samples may be stored in a coded form 
for no more than 2 years after final study report completion and then the samples will 
subsequently be destroyed.
For this study, no samples will be taken or stored long-term in a biobank for future 
analyses.
12.8 Vital Signs
Vital signs will include body temperature (°C or °F), respiratory rate (breaths/min), pulse 
rate (beats/min), systolic and diastolic blood pressure (mmHg). height (in or cm), and 
weight (lb or kg). 
Height and weight is measured only once at screening.
All other vital signs will be measured at screening and within 30 minutes before and 
30 ±5 minutes after administration of IP, at least on Day1, 2, 3 and 7 until GHEA3 Visit, 
at GHEA3 Visit, the antibody testing Visit, at any unscheduled assessments, and at the 
End of Study Visit. Blood pressure will be measured when subjects are in the
supine position.
Vital sign values are to be recorded on the CRF. For each abnormal vital sign value, the 
Investigator will determine whether or not to report an AE (see definition in Section 12.1
and record the medical diagnosis (preferably), symptom, or sign on the AE CRF). 
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
Investigator.
12.9 Karnofsky Performance Test
The Karnofsky Performance Test is a status scale (0 to 100) utilized to measure the level 
of activity and medical care requirements in subjects. It is an Investigator based 
assessment of patient status which evaluates the subjects’ ability to carry on normal life 
activities, as well as the symptoms of their disease.19 Subjects will be scored using this 
scale at screening.
For non-commercial use only

BAX 802
Page 74 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
12.10 Special Treatment Considerations
Patients will be screened for eligibility in the study as described in the 
inclusion/exclusion criteria (Section 9.1 and Section 9.2), and will be informed of the 
study specific restrictions and requirements of the study. Patients who are not willing to 
comply with the study requirements and restrictions of the study will not be eligible for 
enrollment.
All biological agents carry the risk of systemic allergic/hypersensitivity reactions. 
Clinical manifestations of these reactions may include, but are not limited to:

skin rash

pruritus (itching)

urticaria (hives)

angioedema (e.g., swelling of the lips and/or tongue)

anaphylactic reaction.
Proteins may also cause redness, itching, swelling, or pain locally at the infusion site.
Sometimes, these reactions can be life-threatening. Therefore, all patients should be 
closely monitored for signs or symptoms that could result from such reactions, educated 
on the signs or symptoms of these types of reactions, and instructed to contact the study 
site immediately if any of the symptoms are experienced following an injection. 
If a patient experiences an acute allergic/hypersensitivity reaction after an injection of IP, 
he should be managed appropriately and given instruction to receive relevant supportive 
care. Additionally, for an event judged by the Investigator to be a potential systemic 
allergic/hypersensitivity reaction, blood samples will be collected for anti-pFVIII, anti 
hFVIII, and anti-BHK binding antibodies. Serious adverse events related to development 
or worsening of inhibitors are described in Section 12.1.1.1.1.
Patients who experience a potentially severe allergic reaction will be discontinued from 
study drug, they will complete an End of Study Visit, and will be monitored for 
stabilization, or resolution of the AE. Premedication to prevent allergic reactions will not 
be permitted as severe allergic reactions are an outcome measure for this study. 
For non-commercial use only

BAX 802
Page 75 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13. STATISTICS
All details regarding the statistical analysis and the preparation of tables, listings, and 
figures will be described in the statistical analysis plan (SAP). 
13.1 Sample Size and Power Calculations
The total sample size for the study is 12 evaluable subjects, which includes at least 
12 surgeries/procedures in 12 evaluable male subjects (at least 5 major 
surgeries/procedures in 5 evaluable subjects) and at least 2 of the 12 subjects are 
adolescents (≥ 12 to < 18 years old). The sample size, as defined in the protocol, was 
chosen to provide sufficient evidence of safety and effectiveness for this indication and is 
not based on statistical considerations.
Evaluable subjects are defined as subjects who met all study entry criteria and who had at 
least 1 hemostatic efficacy assessment as per Section 8.4.1.
13.2 Analysis Sets
Classification into the analysis sets will be conducted prior to the database lock.
13.2.1 Safety Analysis Set
The safety analysis set (SAS) will be comprised of all subjects who received any amount 
of BAX 802.
13.2.2 Efficacy Datasets
13.2.2.1 Full Analysis Set 
The FAS will be comprised of all surgeries with at least 1 available hemostatic 
assessment.
13.2.2.2 Per-Protocol Analysis Set
The per-protocol (PPAS) analysis set will be comprised of all surgeries with evaluable 
ratings for all 3 perioperative hemostatic efficacy assessments, whose subjects met all 
study entry criteria and had no major protocol violations that might impact hemostatic 
efficacy assessments.
For non-commercial use only

BAX 802
Page 76 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.3 Handling of Missing, Unused, and Spurious Data
A subject who withdraws prior to the last planned observation in a trial period will be 
included in the analyses up to the time of withdrawal.
For surgeries with ≤2 missing hemostatic assessments that did not necessitate rescue 
therapies, the rating of “fair” will be imputed for the missing assessment. These surgeries 
will be included in the FAS.
13.4 Methods of Analysis
For qualitative parameters, the population size (N for sample size and n for available 
data) and the proportion (of available data) for each class of parameters will be presented. 
Quantitative parameters will be summarized by the population size (N for sample size 
and n for available data), mean, standard deviation, median, minimum, and maximum 
values.
13.4.1 Primary Outcome Measure
The primary efficacy measure will be the overall assessment of hemostatic efficacy 
assessed intraoperatively and at postoperative Day 1 (postoperative period, i.e., from end 
of surgery to 24 ±6 hours post-surgery) by the surgeon and perioperatively at 24 to 72 
hours after the last perioperative treatment dose of BAX 802 or discharge (whichever is 
earlier) by the Investigator (hemophilia physician), and where possible, by both the 
Investigator and the operating surgeon (assessment by both is strongly recommended), 
and will be the sum of intraoperative, postoperative, and perioperative GHEA scores as
rated “excellent”, “good”, “fair” or “none”. In cases where there are differing 
assessments, the Investigator’s assessment will be used.
Wherever possible (except for intraoperative assessment), bleeding should be assessed by 
both operating surgeon and Investigator. To achieve the hemostatic efficacy success 
criteria, the study needs to achieve a ≥70% rate of hemostatic efficacy assessments with 
an “excellent” or “good” outcome in at least 12 procedures. 
Hemostatic efficacy success is defined as an “excellent” or “good “outcome for ≥70% of 
hemostatic efficacy assessments.
Due to the possibility of a subject undergoing multiple surgeries, the statistical 
analysis of the primary outcome measure will be reported on the by-surgery level 
(i.e., not by the number of subjects). In cases where two or more surgical procedures 
are performed in the same intraoperative settings (under the same anesthesia, 
e.g., bilateral knee replacement) the surgery will be counted as one surgery. 
For non-commercial use only

BAX 802
Page 77 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Blood loss assessment from those surgeries will be assessed as one. In the event that the 
subject is planning to have additional surgery in the future, they will need to complete the 
study and be re-screened again (if > 3 months from the screening) to ensure that they 
continue to meet the eligibility criteria.
Point estimates and corresponding 2-sided exact Clopper-Pearson confidence intervals 
(CIs) at the 95% confidence level will be calculated for the rate of hemostatic efficacy 
assessments with excellent/good outcome for descriptive purposes.
The proportion of all surgeries and of all major surgeries with hemostatic success will be 
reported along with exact 95% CIs. A treatment success will be defined as a rating of 
excellent or good.
The primary efficacy analysis will be based on the FAS population. As a supportive 
analysis, the same analyses will also be carried out on the PPAS population.
A sensitivity analysis based on the first surgery will be performed if more than 20% of 
subjects have multiple surgeries. Any blood loss which is considered as unrelated 
bleeding (defined as any bleeding occurring at a different anatomical site other than the 
surgery site during the postoperative period, see Section 11.2.5) will not be taken into 
account for while making assessment of hemostatic efficacy for the primary efficacy 
measure.
13.4.2 Secondary Outcome Measures 
13.4.2.1 Secondary Hemostatic Efficacy Analysis
Secondary outcome measures will be reported at the surgery level rather than the subject 
level. Descriptive statistics will be used to summarize the actual blood loss and 
transfusion requirements. 
The summary of average daily and total weight-adjusted doses (average through 
postoperative 24 to 72 hours after last perioperative treatment dose of BAX 802 or 
discharge [whichever is earlier]) of BAX 802 per subject as well as the occurrence of 
bleeding episodes will be provided using descriptive statistics. 
The proportion of major surgeries with good or excellent hemostatic score together with 
its 2-sided 95% CI will be reported for descriptive purposes.
The secondary efficacy analysis will be performed on the FAS only.
For non-commercial use only

BAX 802
Page 78 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.2.2 Safety Analysis
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be summarized by presenting the number and proportion of subjects 
having any AE, having an AE in each system organ class, and having each individual AE 
as reported by preferred term. In the summaries, AEs will be counted only once per 
patient. If a patient reports the same AE more than once, it will be counted with its worst 
severity and closest relationship to the study product.
The number of subjects who experienced SAEs and the number of SAEs will be 
tabulated. In addition, the number of subjects who experienced AEs related to IP and the 
number of IP-related AEs will be tabulated and subcategorized for thrombo-embolic
events, inhibitory and total binding antibodies (IgG and IgM) to pFVIII and hFVIII, and 
binding antibodies to BHK proteins.
A listing of all AEs will be presented by subject identifier, age, preferred term, and 
reported term of the AE, duration, severity, seriousness, action taken, outcome, causality 
assessment, onset date, stop date, and medication or non-drug therapy to treat the AE. An 
overview table for AEs will be provided, presenting the number of AEs, the number of 
subjects with AEs and the corresponding percent of subjects in total, and by seriousness 
and relationship to study treatment. An additional summary table will present the total 
number of (mild, moderate, severe) AEs by system organ class and preferred term with 
relationship to IP.
Summary statistics over time will be presented for the continuous laboratory parameters. 
Descriptive statistics of changes from baseline (prior to BAX 802 loading dose before the 
surgery) by study visits will also be presented.
A frequency table of results of categorical laboratory parameters will be produced. 
Furthermore, laboratory abnormalities will be analyzed by shift tables where each subject 
will be counted only once with the worst grade in the summary tables. 
All laboratory data will be listed with abnormal values.
Vital signs assessments as well as the corresponding changes from baseline will be 
summarized descriptively at each scheduled or unscheduled assessment.
The safety analysis will be based on the SAS.
For non-commercial use only

BAX 802
Page 79 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
13.4.1 Exploratory Outcome Measures 
 
.
 
 
.
 
. 
 
 
.
Further details will be included in the SAP.
13.5 Planned Interim Analysis of the Study
No interim analyses are planned for this study.
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The Investigator/study site will cooperate and provide direct access to study documents 
and data, including source documentation for monitoring by the study monitor, audits by
the sponsor or sponsor’s representatives, review by the Institutional Review Board (IRB) 
or Ethics Committee (EC), and inspections by applicable regulatory authorities, as 
described in the Clinical Trial Agreement (CTA). If contacted by an applicable regulatory
authority, the Investigator will notify the sponsor of contact, cooperate with the authority, 
provide the sponsor with copies of all documents received from the authority, and allow 
the sponsor to comment on any responses, as described in the CTA.
For non-commercial use only

BAX 802
Page 80 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The Investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable national and local regulatory requirements 
as described in the CTA. The Investigator is ultimately responsible for the conduct of all 
aspects of the study at the study site and verifies by signature the integrity of all data 
transmitted to the sponsor. The term “Investigator” as used in this protocol as well as in 
other study documents, refers to the Investigator or authorized study personnel that the 
Investigator has designated to perform certain duties. Sub-Investigators or other 
authorized study personnel are eligible to sign for the Investigator, except where the 
Investigator’s signature is specifically required.
15.1.1 Investigator Report and Final Clinical Study Report
The Investigator, or coordinating Investigator(s) for multicenter studies, will sign the 
clinical study report. The coordinating Investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the Investigator and study site personnel understand 
all requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an Investigator. Training may be provided at an Investigator’s meeting, 
at the study site, and/or by instruction manuals. In addition, the study monitor will be 
available for consultation with the Investigator and will serve as the liaison between the 
study site and the sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts 
the study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory
guidelines/requirements. The Investigator will permit the study monitor to visit the study
site at appropriate intervals, as described in the CTA. Monitoring processes specific to 
the study will be described in the clinical monitoring plan.
For non-commercial use only

BAX 802
Page 81 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
15.4 Safety Monitoring
The safety of the subjects in this study shall be monitored by an external DSMB 
comprised of experts in the field of hemophilia research and clinical care.
The DSMB will review safety data at predefined intervals and make recommendations to 
the study team on study conduct including dose escalation and modifications to study 
plan. Details of the composition and responsibilities of the DSMB will be provided in a 
DSMB charter.
15.5 Auditing
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory
guidelines/requirements. The Investigator will permit auditors to visit the study site, as 
described in the CTA. Auditing processes specific to the study will be described in the 
audit plan.
15.6 Non-Compliance with the Protocol
The Investigator may deviate from the protocol only to eliminate an apparent immediate 
hazard to the subject. In the event(s) of an apparent immediate hazard to the subject, the 
Investigator will notify the sponsor immediately by phone and confirm notification to the 
sponsor in writing as soon as possible, but within 1 calendar day after the change is 
implemented. The sponsor (Baxalta) will also ensure the responsible EC and relevant 
competent authority is notified of the urgent measures taken in such cases according to 
local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the sponsor may terminate the Investigator’s participation. The sponsor will 
notify the EC and applicable regulatory authorities of any Investigator termination.
15.7 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments. Local 
laboratories are requested to provide their laboratory specifications for each assay used.
For non-commercial use only

BAX 802
Page 82 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16. ETHICS
16.1 Subject Privacy
The Investigator will comply with applicable subject privacy regulations/guidance as 
described in the CTA.
16.2 Ethics Committee and Regulatory Authorities
Before patients participate in this study, the protocol, informed consent form, any
promotional material/advertisements, and any other written information will be reviewed 
and approved/given favorable opinion by the EC and applicable regulatory authorities. 
The IB will be provided for review. The EC’s composition or a statement that the EC’s 
composition meets applicable regulatory criteria will be documented. The study will 
commence only upon the sponsor’s receipt of approval/favorable opinion from the EC 
and, if required, upon the sponsor’s notification of applicable regulatory authority(s) 
approval, as described in the CTA.
If the protocol or any other information given to the subject is amended, the revised 
documents will be reviewed and approved/given favorable opinion by the EC and 
applicable regulatory authorities, where applicable. The protocol amendment will only be 
implemented upon the sponsor’s receipt of approval and, if required, upon the sponsor’s 
notification of applicable regulatory authority(s) approval.
16.3 Informed Consent
Investigators will choose patients for participation considering the study eligibility
criteria. The Investigator will exercise no selectivity so that no bias is introduced from 
this source.
All patients and/or their legally authorized representative must sign an ICF before 
entering into the study according to applicable national and local regulatory requirements 
and ICH GCP. An assent form may be provided and should be signed by patients less 
than 18 years of age. Before use, the ICF will be reviewed by the sponsor and approved 
by the EC and regulatory authority(s), where applicable, (see Section 16.2). The ICF will 
include a comprehensive explanation of the proposed treatment without any exculpatory
statements, in accordance with the elements required by ICH GCP and applicable 
national and local regulatory requirements. Patients or their legally authorized 
representative(s) will be allowed sufficient time to consider participation in the study. By
signing the ICF, patients or their legally authorized representative(s) agree that they will 
complete all evaluations required by the study, unless they withdraw voluntarily or are 
terminated from the study for any reason.
For non-commercial use only

BAX 802
Page 83 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
The sponsor will provide to the Investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The ICF will be 
updated, if necessary. This new information and/or revised ICF that has been approved by 
the applicable EC and regulatory authorities, where applicable, will be provided by the 
Investigator to the subjects who consented to participate in the study (see Section 16.3).
For non-commercial use only

BAX 802
Page 84 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The Investigator will comply with the confidentiality policy as described in the CTA. 
17.2 Study Documentation and Case Report Forms
The Investigator will maintain complete and accurate paper format study documentation 
in a separate file. Study documentation may include information defined as “source data” 
(see Section 8.8), records detailing the progress of the study for each subject, signed 
informed consent forms, correspondence with the EC and the study monitor/sponsor, 
screening information, CRFs, SAERs, laboratory reports (if applicable), and data 
clarifications requested by the sponsor.
The Investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry 
will be crossed out entirely, remaining legible; and 2) each correction must be dated and 
initialed by the person correcting the entry; the use of correction fluid and erasing are 
prohibited.
The Investigator is responsible for the procurement of data and for the quality of data 
recorded on the CRFs. CRFs will be provided in electronic form.
If electronic format CRFs are provided by the sponsor, only authorized study site 
personnel will record or change data on the CRFs. If data is not entered on the CRFs 
during the study visit, the data will be recorded on paper, and this documentation will be 
considered source documentation. Changes to a CRF will require documentation of the 
reason for each change. An identical (electronic/paper) version of the complete set of 
CRFs for each subject will remain in the Investigator file at the study site in accordance 
with the data retention policy (see Section 17.3).
The handling of data by the sponsor, including data quality assurance, will comply with 
regulatory guidelines (e.g., ICH GCP) and the standard operating procedures of the 
sponsor. Data management and control processes specific to the study will be described 
in the data management plan.
17.3 Document and Data Retention 
The Investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention 
policy, as described in the Clinical Study Agreement.
For non-commercial use only

BAX 802
Page 85 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
18. FINANCING AND INSURANCE
The Investigator will comply with Investigator financing, Investigator/sponsor insurance, 
and subject compensation policies, if applicable, as described in the CTA.
19. PUBLICATION POLICY
The Investigator will comply with the publication policy as described in the CTA. 
For non-commercial use only

BAX 802
Page 86 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20. SUPPLEMENTS
20.1 Procedures per Study Period
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502
1. Screening
Written Informed Consent must be obtained prior to any study-related procedures
Screening activities should be performed within 45 days prior to the planned elective surgery.
The following screening procedures are required:

Eligibility evaluation (review of inclusion/exclusion criteria)

Relevant medical and surgical history (including Hemophilia history, bleeding episode history, 
history of aPCC or rFVIIA usage for 6 months prior to screening)

Review of concomitant medications/non-drug therapies and all medications taken 3 months prior to 
screening

Physical examination (see Section 12.6)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and measure body weight 
and height; see Section 12.8)

Karnofsky performance test assessment (see Section 12.9)

Clinical laboratory assessments (see Table 10).
For non-commercial use only

BAX 802
Page 87 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502
2. Preoperative Procedures
Subjects will return to the study site prior to their scheduled surgery as instructed by site staff. Subjects will 
undergo the following procedures:
Prior to surgery
The following procedures should be performed before surgery and must be available by at the latest 2 hours 
before the start of surgery:

Accurate prediction of volume of expected blood loss intraoperatively (from completion of the 
procedure until approximately 24 hours post-surgery) and for the overall perioperative time period 
(up to 24 to 72 hours after the last perioperative treatment dose of BAX 802 or discharge), which is 
to be timestamped into the source documentation and/or blood loss form prior to the surgery.
Loading Dose and Post Dosing Laboratory Assessment
Within 1 to 2 hours before initiating surgery, the subject will receive a loading dose of BAX 802 to raise 
the plasma level of FVIII to ≥80% for major and to ≥50% for minor surgical, dental and invasive 
procedures.
Subjects will undergo the following procedures:

Prior to BAX 802 loading dose:

Record AEs, concomitant medications, and non-drug therapy use

Physical examination

Vital signs (pulse rate, respiratory rate, blood pressure, and temperature) 

Laboratory Assessments including:
o
Hematology (without differential but including platelets)
o
Clinical chemistry  
o
Within 30 minutes before loading dose, blood draw for:

FVIII activity 

BAX 802 loading dose:

Loading dose of BAX 802 to raise the plasma level of FVIII to ≥80% of normal for major and 
to ≥50% for minor surgical, dental and invasive procedures. It will be administered within 1 to 
2 hours prior to surgery (prior to incision/intubation). 

After BAX 802 loading dose:

Laboratory assessment of FVIII activity: 30 ±5 minutes after infusion of the loading dose

Vital signs (pulse, respiratory rate, blood pressure and temperature) will be recorded 
30 ±5 minutes after infusion

Confirmation that FVIII is adequate just prior to intubation/incision. Administration of 
additional dose of BAX 802, if required. If another dose of BAX 802 is necessary, an additional 
post-infusion FVIII activity determination must be performed 30 ±5 minutes following the 
infusion.

All samples taken through 6 hours post-infusion will be collected from an extremity other than 
that used for the infusion of study product. Thereafter, either extremity may be used to obtain 
samples.
The surgery may begin only if FVIII is in target range (Table 5 and Section 8.7.3.3.2).
Throughout: Monitoring of AEs and concomitant medication and non-drug therapy use.
For non-commercial use only

BAX 802
Page 88 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502
3. Intraoperative Procedures (end of surgery = Day 0)
During the surgical procedure:

Record AEs and concomitant medication and non-drug therapy use

Record blood product usage, (e.g. whole blood, red blood cells, platelets and plasma. 

Administer additional BAX 802 infusions according to the dosing regimen (Table 5) 

Record intraoperative blood loss and transfusion requirements
If the subject has excessive or unexplained bleeding, draw blood for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary, subjects 
switching to rescue medication are required to come to the End of study Visit 42 ± 7 days following the last 
perioperative dose of BAX 802. 
After the surgical procedure:

Record the volume of blood loss during surgery and amount of total blood product usage, (e.g. 
whole blood, red blood cells, platelets and plasma Assess intraoperative hemostatic efficacy (Global
Hemostatic Efficacy Assessment, GHEA1, Table 2) (at the end of surgery) 

Take sample for FVIII activity immediately after surgery completion, with dose adjustments as 
necessary on the day of surgery (see Section 10.5)

Take sample for FVIII activity within preferably 4 to 6 hours following surgery, with dose 
adjustments as necessary on the day of surgery (see Section 10.5)
If the subject has excessive or unexplained bleeding, draw blood for FVIII activity. Treat by whatever 
means necessary until adequate hemostasis is achieved. If rescue medications become necessary (see 
Section 10.5), subjects switching to rescue medication are required to come to the End Of study Visit  42 ± 
7 days following the last perioperative dose of BAX 802.
For non-commercial use only

BAX 802
Page 89 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502
4. Postoperative Procedures (Day 1 to GHEA3 Visit)

For subjects undergoing major surgery: keep pre-infusion FVIII levels at least at 80% of normal for 
the first postoperative 72 hours and at least at 50% during postoperative Day 4 to Day 7. It is 
recommended that the FVIII levels do not fall below 30% from Day 8 until GHEA3 Visit.

For subjects undergoing minor surgery: keep pre-infusion FVIII levels at least at 50% of normal for 
the first postoperative 72 hours. It is recommended that the FVIII levels do not fall below 30% from 
Day 4 onwards (if not yet discharged and GHEA3 not yet performed).
From Postoperative Day 1 (i.e., the day following the day of the surgical/invasive procedure), 
and daily until the GHEA3 Visit the following assessments will be performed:

Record AEs and concomitant medication and non-drug therapy use

Record blood loss on a daily basis and at drain removal, if applicable

Record transfusion requirements

GHEA:
o
GHEA2 (Table 3): assessment of postoperative hemostatic efficacy of BAX 802
performed at Day 1 by the operating surgeon/Investigator
o
GHEA3 (Table 4): assessment of perioperative hemostatic efficacy of BAX 802 at 24 to 
72 hours after the last perioperative treatment dose of BAX 802 or discharge (whichever 
is earlier) performed by the Investigator, and where possible, also by the operating 
surgeon
In cases such as minor surgeries/procedures, there might be a possibility that the subject is 
discharged < 24 hours following the surgery/procedure but continues receiving BAX 802 in 
hospital (e.g., day hospital) setting. In these cases, the GHEA2 hemostatic efficacy assessment 
should be performed the following day. Also, the GHEA3 Visit should be performed within 24 
to 72 hours after the last perioperative treatment dose of BAX 802. Both GHEA2 and GHEA3 
assessments can be performed on the day after the surgery/procedure if the subject does not 
need any further BAX 802 administration for perioperative management.

Perform physical examination and vital signs as per Table 9.

Blood draws for FVIII activity determination and hematology should be performed coincident 
with an early morning dose to the greatest extent possible.

FVIII activity assays at the local and the central laboratories as per Section 8.7.3.3.3. Additional 
BAX 802 doses will be administered as per Table 5. FVIII activity assays pre infusion (within 
30 minutes) and post infusion (30 ±5 minutes) for each IP administration, and at other time 
points as deemed necessary by the surgeon or Investigator throughout the study 
o
1-stage clotting and chromogenic for the central laboratory
o
1-stage clotting for local laboratories

Samples for laboratory testing will be taken daily during Day 1 to 7 post-surgery and then 
subsequently once weekly:
o
Hematology
o
Clinical chemistry

If the subject has excessive or unexplained bleeding, draw blood for FVIII activity. Treat by 
whatever means necessary until adequate hemostasis is achieved. If rescue medications become 
necessary, subjects switching to rescue medication are required to come to the End of study Visit 42 
± 7 days following the last perioperative dose of BAX 802.
For non-commercial use only

BAX 802
Page 90 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502

If the subject is discharged from surgical facility on the day of the procedure, he should attend the 
site on Day 1 to perform the postoperative hemostatic efficacy assessment (Day 1 assessment) and 
the overall perioperative assessment. In this case, physical examination, vital signs, laboratory 
assessments, adverse events, and concomitant medications must also be assessed. If the subject is 
discharged from surgical facility after Day 1 but prior to the overall perioperative assessment, he 
should return to the site for that assessment as well as the required physical examination, vital signs, 
laboratory assessments, adverse events, and concomitant medications assessments.
5. GHEA3 Visit
The perioperative hemostatic efficacy assessment (GHEA 3) will be performed 24 to 72 hours after the last 
perioperative treatment dose of BAX 802 or at discharge, whichever is earlier. In cases such as minor 
surgeries/procedures, there might be a possibility that the subject is discharged < 24 hours following the 
surgery/procedure but continues receiving BAX 802 in hospital (e.g., day hospital) setting. In these cases, 
the GHEA2 hemostatic efficacy assessment should be performed the following day. Also, the GHEA3 Visit 
should be performed within 24 to 72 hours after the last perioperative treatment dose of BAX 802. Both 
GHEA2 and GHEA3 assessments can be performed on the day after the surgery/procedure if the subject 
does not need any further BAX 802 administration for perioperative management.
Procedures to be performed for each subject at GHEA 3 Visit:

Assessment of blood loss

Assessment of transfusion requirements

Review of concomitant medications/non-drug therapies

physical examination 

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate)

Clinical laboratory assessments (Table 10)

Immunogenicity assays:

 

Anti-BHK binding antibody titers
6. Antibody Testing Visit
A visit will be performed between 7 to 14 days after the last perioperative treatment dose of BAX802. 
Study procedures will be performed as per Table 9 and blood samples will be collected for antibody testing 
and other tests as per Table 10. De novo or clinically significant increases in antibodies will require a 
confirmatory blood sample collection 7 to 14 days after the initial positive result.
Procedures to be performed for each subject at Antibody Testing Visit:

Immunogenicity assays:

 
(Note: these will be performed only if at least 72 hours must have elapsed 
since the previous BAX 802 administration)
Anti-BHK binding antibody titers
For non-commercial use only

BAX 802
Page 91 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 8
Summary of Required Procedures for Baxalta Clinical Study 241502
7. End of Study [EOS] Visit (42 ± 7 days of last dose of BAX 802)
EOS Visit will be performed 42 ± 7 days following the last perioperative dose of Bax802. 
Procedures to be performed for each subject at EOS Visit:

Assessment of blood loss

Assessment of transfusion requirements

Review of concomitant medications/non-drug therapies

physical examination 

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate)

Clinical laboratory assessments (Table 10)

Immunogenicity assays:

 
Anti-BHK binding antibody titers
Unrelated Bleeding Episodes During the Postoperative Period:
An unrelated bleeding episode is defined as any bleeding occurring at a different anatomical site than the 
surgery site during the postoperative period. Refer to Section 11.2.5, Table 9, and Table 10.
For non-commercial use only

BAX 802
Page 92 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.2 Study Flow Chart
Figure 2
Visit Schedule
                                                                                                                                                                                                
                                                                                                                                                                                        45 days 
                                                                                                                                                                         1 day
                                                                                                                                                                      variable
                                                                                                                                                                      42±7 days post last dose
Enrollment Screening
Pre-op procedures
Surgery (Day 0)
Post-op procedures (Day 1 and daily 
until discharge)
EOS visit + Inhibitor assessment
I/E criteria confirmed, including anti-
human and anti-porcine FVIII titer 
assessment
Discharge
For non-commercial use only

BAX 802
Page 93 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.3 Schedule of Study Procedures and Assessments
Table 9
Schedule of Study Procedures and Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Procedures for 
Unrelated/Surgical 
Site Bleeding 
Episodes During 
the Postoperative 
Period (see Sections 
11.2.3 and 11.2.5)d
Visit
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures
Antibody Testing 
Visita
End of Study 
Visitb
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During 
surgery
Day 1 and daily 
thereafter until 
GHEA3c
7 to 14 days after 
last perioperative 
treatment dose of 
BAX 802
42 ± 7 days after 
last perioperative 
treatment dose of 
BAX 802
Eligibility criteria, 
including medical historye
X
Prediction of 
intraoperative blood lossf
X
Medications and non-drug 
therapies
X
X
X
X
X
X
X
Physical examination
X
X
Xg (as required)
X
X
Adverse events
X
X
X
X
X
X
Laboratory assessmentsh
X
Xi
X
Xj
X
X
X
Vital signsk
X
X
X
X
X
X
Karnofsky Performance 
Test
X
Approved FVIII 
maintenance plan
X
For non-commercial use only

BAX 802
Page 94 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 9
Schedule of Study Procedures and Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Procedures for 
Unrelated/Surgical 
Site Bleeding 
Episodes During 
the Postoperative 
Period (see Sections 
11.2.3 and 11.2.5)d
Visit
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures
Antibody Testing 
Visita
End of Study 
Visitb
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During 
surgery
Day 1 and daily 
thereafter until 
GHEA3c
7 to 14 days after 
last perioperative 
treatment dose of 
BAX 802
42 ± 7 days after 
last perioperative 
treatment dose of 
BAX 802
IP treatment
X (loading 
dose; Table 5)
X (as required; 
Table 5)
X (as required; 
Table 5)
Refer to Table 6
Hemostatic Efficacy 
Assessments (GHEA1, 
GHEA2, and GHEA3)
GHEA1 at the 
end of surgery 
as per Table 2
GHEA2 at 12 to 
24 hours (Day 1) as 
per Table 3
GHEA3 at 24 to 
72 hours after the last
perioperative 
treatment dose of 
study drug is 
administered or 
discharge (whichever 
is earlier), as per 
Table 4
At 24 ±2 hours after 
the initiation of 
treatment and at the 
resolution of bleed 
(if not resolved 
within 24 hours) 
using a 4-point 
efficacy rating scale 
(Table 7)
Transfusion requirements
and blood lossl
X
X
X
X
Continued on Next Page
For non-commercial use only

BAX 802
Page 95 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
Key: EOS = End of Study Visit; OR = operating room
a The Antibody Testing Visit is required. Any de novo (> 0.6 BU) or significantly increased (> 10 BU) results will require confirmatory blood assessments 
an additional 7 to 14 days later, which is to include the procedures identified here with data recorded as an unscheduled visit.
b The End of Study Visit also applies to subjects who withdraw or discontinue prematurely. 
c If the subject is discharged from surgical facility on the day of the procedure, he should return to the site on Day 1 to perform the postoperative 
hemostatic efficacy assessment (Day 1 assessment) and the overall peri-operative assessment. In this case, physical examination, vital signs, laboratory 
assessments, adverse events, and concomitant medications/non-drug therapies must also be assessed. If the subject is discharged from surgical facility 
after Day 1 but prior to the overall peri-operative assessment, he should return to the site for that assessment as well as the required physical examination, 
vital signs, laboratory assessments, adverse events, and concomitant medications assessments.
d May also be collected as an unscheduled visit.
e Occurs prior to any study-specific procedures; as per Section 12.5, includes hemophilia history, bleeding episode history, history of aPCC or rFVIIA 
usage for 6 months prior to screening.
f Preoperative prediction of expected blood loss for a subject with severe hemophilia A with inhibitors and a comparable healthy individual with the same 
demographic characteristics will be estimated and documented as per Section 11.2.1. This could also be performed days/weeks before the surgery, during 
the screening period.
g Perform physical examination (see Section 12.6) on Days 1, 2, 3, and 7 post surgery (if a subject remains admitted).
h For laboratory assessments, see Table 10.
i Within 30 minutes pre-dose and 30 ±5 minutes post-dose for FVIII activity.
j Blood draws for FVIII activity determination (see Section 11.3) and hematology should be performed coincident with an early morning dose to the 
greatest extent possible. Samples for laboratory testing (hematology and clinical chemistry) will be taken daily until GHEA 3-Visit from Day 1 through 7 
post-surgery and then subsequently once weekly. 
k Vital signs (see Section 12.8) will include body temperature, pulse rate, blood pressure, respiratory rate. Blood pressure will be measured when subjects 
are in the supine position. Height and weight will be measured once at Screening.  Vital signs will be measured generally at 30 minutes before and 
30 ± 5 minutes after each administration of IP. In addition it needs to be measured at Screening, on Days 1, 2, 3 and 7 post surgery (if a subject remains 
admitted), at the AntibodyTestingVisit and the End of study Visit.
l Record blood loss on a daily basis and at drain removal; record blood product usage, whole blood, red blood cells, platelets and plasma
For non-commercial use only

BAX 802
Page 96 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.4 Clinical Laboratory Assessments
Table 10
Clinical Laboratory Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Laboratory 
Assessments for 
Unrelated/Surgical 
Site Bleeding 
Episodes During 
the Postoperative 
Period (see 
Section 11.2.5)c
Visit
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures
Antibody 
Testing Visita
End of Study 
Visitb
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During surgery
Day 1 and daily 
thereafter until 
GHEA3
7-14 days after 
last 
perioperative 
treatment dose 
of BAX 802
42 ± 7 days after 
last 
perioperative 
treatment dose 
of BAX 802
FVIII activity 
(clotting and
chromogenic assay 
at central laboratory; 
clotting assay at 
local laboratory)
Citrated 
plasma
C
L and C within 
30 minutes 
before loading 
dose, then 
30 ±5 minutes 
after loading 
dosed
Optional 
sampling, as 
deemed 
necessary: 
L and C
Also, if subject 
has excessive or 
unexplained 
bleeding
L and Ce
L and C
Optional sampling, 
as deemed 
necessary: L and C
PT and aPTT
Citrated 
plasma
C and L
Chemistryf
Serum
C
L and C
(L)
L
Daily Days 1 to 7
C (L)
C (L)
For non-commercial use only

BAX 802
Page 97 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Table 10
Clinical Laboratory Assessments
Period
Screening
Preoperative
Intraoperative
Postoperative
End of Study
Laboratory 
Assessments for 
Unrelated/Surgical 
Site Bleeding 
Episodes During 
the Postoperative 
Period (see 
Section 11.2.5)c
Visit
Screening
Preoperative 
procedures
Intraoperative 
procedures
Postoperative: 
Daily procedures
Antibody 
Testing Visita
End of Study 
Visitb
Time point
Up to 
45 days 
prior to 
Day 0
Day 0
~60 to 120 
minutes prior 
to surgery
Day 0
During surgery
Day 1 and daily 
thereafter until 
GHEA3
7-14 days after 
last 
perioperative 
treatment dose 
of BAX 802
42 ± 7 days after 
last 
perioperative 
treatment dose 
of BAX 802
Hematology
Whole 
blood
Cg
Lh
(L)
L
Daily Days 1 to 7
C (L)
C (L)
Urinalysis
Urine
C
C
C
Viral serologyi
Serumj
C
 
 
 
 
 
Citrated 
plasma
Cg
C
C
Anti-BHK binding 
Antibody titers
Citrated 
plasma
C
C
C
Continued on Next Page
For non-commercial use only

BAX 802
Page 98 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
Continued
Key: C = central laboratory; EOS = End of Study Visit; L = local laboratory; (L) = local testing optional, to aid in clinical management of patients.
a The Antibody Testing Visit is required. Any de novo (> 0.6 BU) or significantly increased (> 10 BU) results will require confirmatory blood assessments 
an additional 7 to 14 days later, which is to include the procedures identified here with data recorded as an unscheduled visit.
b The End of Study Visit also applies to subjects who withdraw or discontinue prematurely. 
c May also be collected as an unscheduled visit.
d It is recommended that the surgery starts after FVIII levels have achieved target levels. If FVIII activity post loading dose is close to the target level, a 
supplement dose of BAX 802 should be administered without further delaying the surgery. If FVIII activity post loading dose is not close to the target 
level, a supplement dose of BAX 802 should be administered and surgery delayed until FVIII levels have achieved target levels or are in close range.
e FVIII activity should be monitored postoperatively as per instructions in Table 5 and Section 8.7.3.3.3.
f Sodium, potassium, chloride, bicarbonate, protein, albumin, ALT, AST, total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and 
glucose.
g Hematology and antibody testing should be performed during screening at least 2 weeks before the planned surgery day as hematocrit and anti-pFVIII 
inhibitor titer values are required for loading dose calculation.
h Hematology, without differential but including platelets.
i HIV-1 and HIV-2 antibody, HAV (IgM and total antibodies), HBsAg, HBsAb, HBcAb, HCV Ab, and parvovirus B19 (IgM and IgG antibodies). CD4 
for HIV positive patients and HCV-RNA or HIV-RNA for 
confirmatory testing of HIV or HCV positive results, respectively.
j Citrated plasma for HCV-RNA or HIV-RNA confirmatory testing.
For non-commercial use only

BAX 802
Page 99 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.5 Global Efficacy Assessments Scores
Table 11
Combinations of Individual Efficacy Assessments
(GHEA1, GHEA2, and GHEA3) and GHEA Score
Individual 
Assessment Scores
(GHEA1, GHEA2, and GHEA3)
GHEA
3 3 3
Excellent
3 3 2
Excellent
3 2 2
Excellent
3 3 1
Good
3 2 1
Good
3 1 1
Good
2 2 2
Good
2 2 1
Good
2 1 1
Fair
1 1 1
Fair
3 3 0
None
3 2 0
None
3 1 0
None
3 0 0
None
2 2 0
None
2 1 0
None
2 0 0
None
1 1 0
None
1 0 0
None
0 0 0
None
For non-commercial use only

BAX 802
Page 100 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
20.6 Definitions
20.6.1 Joint Bleeds
Features of an acute joint bleed include some or all of the following: ‘aura’, pain, 
swelling, warmth of the skin over the joint, decreased range of motion and difficulty in 
using the limb compared with baseline or loss of function. 
The earliest clinical signs of a joint bleed are increased warmth over the area and 
discomfort with movement, particularly at the ends of range.
Later symptoms and signs include pain at rest, swelling, tenderness, and extreme loss of 
motion.
In patients with advanced arthropathy it may be difficult to distinguish pain-related 
arthritis from that associated with an acute bleed. Rapid resolution of pain following 
infusion of factor concentrates (typical of an acute hemarthrosis) or improvement of pain 
associated with activity soon after a period of rest (typical of chronic arthritis) can help 
distinguish between the two.
20.6.2 Muscle Bleeds
Muscle bleeds can occur in any muscle of the body, usually from a direct blow or a 
sudden stretch. A muscle bleed is defined as an episode of bleeding into a muscle, 
determined clinically and/or by imaging studies, generally associated with pain and/or 
swelling and functional impairment over baseline.
For further definitions of central nervous system, gastrointestinal, and abdominal 
hemorrhages see the Guidelines for the management of hemophilia from the WFH.5,20
For non-commercial use only

BAX 802
Page 101 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
21. REFERENCES
1.
Coppola A, Di Capua M, Di Minno MND, et al. Treatment of hemophilia: A 
review of current advances and ongoing issues. J Blood Med. 2010;1:183-195.
2.
Janbain M, Leissinger CA, Kruse-Jarres R. Acquired hemophilia A: emerging 
treatment options. J Blood Med. 2015;6:143-150.
3.
Mansouritorghabeh H. Clinical and laboratory approaches to hemophilia A. Iran J 
Med Sci. 2015;40(3):194-205.
4.
Berntorp E, Shapiro A, Astermark J, et al. Inhibitor treatment in haemophilias A 
and B: summary statement for the 2006 international consensus conference. 
Haemophilia. 2006;12 Suppl 6:1-7.
5.
World Federation of Hemophilia Treatment Guidelines Working Group. Guidelines 
for the management of hemophilia 2nd Edition. Guidelines for the management of 
hemophilia 2nd Edition; 2012:80. Web Link: 
http://www1.wfh.org/publication/files/pdf-1472.pdf
6.
Santagostino E, Escobar M, Ozelo M, et al. Recombinant activated factor VII in the 
treatment of bleeds and for the prevention of surgery-related bleeding in congenital 
haemophilia with inhibitors. Blood Rev. 2015;29 Suppl 1:S9-S18.
7.
Valentino LA, Cooper DL, Goldstein B. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX. Haemophilia 589. Vol. 17. Surgical experience with rFVIIa 
(NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors 
VIII or IX; 2011:11-579. Web Link: 
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2516.2010.02460.x/epdf
For non-commercial use only

BAX 802
Page 102 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
8.
Kempton CL, White GC, II. How we treat a hemophilia A patient with a factor VIII 
inhibitor. Blood. 2009;113(1):11-17.
9.
Kasper CK. Effect of prothrombin complex concentrates on factor VIII inhibitor 
levels. Blood. 1979;54:1358-1368.
10.
Young G, Sørensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS. 
Thrombin generation and whole blood viscoelastic assays in the management of 
hemophilia: current state-of-art and future perspectives. Blood. 2013;121(11):1944-
1950.
11.
Kempton CL, Abshire TC, Deveras RA, et al. Pharmacokinetics and safety of OBI-
1, a recombinant B domain-deleted porcine factor VIII, in subjects with 
haemophilia A. Haemophilia. 2012;18(5):798-804.
12.
Mahlangu JN, Andreeva TA, Macfarlane DE, Walsh C, Key NS. Recombinant B-
domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of 
bleeding in patients with congenital haemophilia A and inhibitors. Haemophilia. 
2017;23(1):33-41.
13.
Kruse-Jarres R, St Louis J, Greist A, et al. Efficacy and safety of OBI-1, an 
antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with 
acquired haemophilia A. Haemophilia. 2015;21(2):162-170.
14.
Brettler DB, Forsberg AD, Levine PH, et al. The use of porcine factor VIII 
concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor 
VIII. A multicenter US experience. Arch Intern Med. 1989;149(6):1381-1385.
15.
Hay CRM, Lozier JN, Lee CA, et al. Safety profile of porcine factor VIII and its 
use as hospital and home-therapy for patients with haemophilia-A and inhibitors: 
the results of an international survey. Thromb Haemost. 1996;75(1):25-29.
For non-commercial use only

BAX 802
Page 103 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
16.
Baxter Healthcare Corporation. Package Insert: OBIZUR [antihemophilic factor 
(recombinant), porcine sequence] lyophilized powder for solution for intravenous 
injection.;2014. Web Link: 
https://www.baxter.com/assets/downloads/obizur_pI.pdf
17.
Lee CA. The evidence behind inhibitor treatment with porcine factor VIII. 
Pathophysiol Haemost Thromb. 2002;32 Suppl 1:5-8.
18.
Kasper C. Diagnosis and Management of Inhibitors to Factors VIII and IX - An 
Introductory Discussion for Physicians. Vol. 34. Diagnosis and Management of 
Inhibitors to Factors VIII and IX - An Introductory Discussion for Physicians: 
World Federation of Hemophilia (WFH); 2004:22. Web Link: 
http://www1.wfh.org/publications/files/pdf-1178.pdf
19.
Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents 
in cancer. In: MacLeod CM, ed. Evaluation of Chemotherapeutic Agents. New 
York: Columbia University Press; 1949:191-205.
20.
Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, 
Srivastava A. Definitions in hemophilia: Communication from the SSC of the 
ISTH. J Thromb Haemost. 2014;12(22):1935-1939.
For non-commercial use only

BAX 802
Page 104 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
22. SUMMARY OF CHANGES 
Protocol 241502: Amendment 6, 2017 DEC 14
Replaces: Amendment 4, 2017 JUN 28
In this section, changes from the previous version of the Protocol Amendment 4, dated 
2017 JUN 28, are described and their rationale is given.
1.
Throughout the document
Description of Change: Minor editorial changes to align with most current protocol 
template version, to update the list of abbreviations, administrative changes to the 
study team, and for improved clarity and consistency. 
Purpose of Change: For consistency with the current Baxalta protocol template, and 
to improve clarity and consistency (note: minor edits and deletions that do not 
substantively change the protocol or are administrative in nature are not 
individually listed below). Note that changes that are found in the synopsis and 
more than one section in the body may have minor differences in wording; the 
common substantive changes are presented here.
2.
Throughout the document
Description of Change: the utilization and the definition of the term “blood 
products” was harmonized throughout the protocol. 
Purpose of Change: For greater clarity and consistency
3.
Section 2 “SAE Reporting”
Description of Change: the standard protocol template text describing the SAE 
reporting process was made more specific.
Purpose of Change: For greater clarity and to prevent any ambiguity
4.
Synopsis; Section 8.3 “Duration of Study Period(s) and Subject Participation” 
Description of Change: the initiation of the trial and the total planned duration of 
the trial were updated. 
Purpose of Change: Information update
For non-commercial use only

BAX 802
Page 105 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
5.
Synopsis; Section 8.3 “Duration of Study Period(s) and Subject Participation”, 
Section 10.4.4 “End of Study Visit” 
Section 10.7 “Subject Completion/Discontinuation”, Table 9 and Table 10
Description of Change: The timing of the End of Study Visit for each patient was 
harmonized throughout the study protocol. 
Purpose of Change: For greater clarity and to prevent any ambiguity
6.
Synopsis, Section 8.4.1 Primary Outcome Measures, 
Section 10.4.1 “GHEA3 Visit” and Table 8 Summary of Required Procedures
Description of Change: Information was added to the description of the GHEA 3 
assessment 
Purpose of Change: For greater clarity and to prevent any ambiguity
7.
Synopsis, Section 8.4.1 Primary Outcome Measures and 
Table 8 “Summary of Required Procedures”
Description of Change: The requirement to return to the site for a GHEA 2 
assessment in case of a discharge within 24 hours after the surgery was introduced.
Purpose of Change: To ensure the GHEA 2 data is collected for each patient
8.
Synopsis and Section 13.4.1 Primary Outcome Measure
Description of Change: Deleted “If discharge is delayed for a reason other than 
surgery related bleeding (e.g., pneumonia), an assessment at 24 to 78 hours after 
last perioperative treatment dose of BAX 802 will ensure that the overall 
perioperative assessment is completed close to the last administered study drug 
dose. “ 
Purpose of Change: To align with the revised definition of the GHEA 3 visit 
9.
8.2.2 “Dose Selection Rationale”,
8.7.3.3 “Dosing Schedule and Requirements” and 
Table 5 “Dosing for Perioperative Management”
Description of Change: The units in which BAX 802 loading dose and anti-pFVIII 
inhibitor titer are expressed were added
Purpose of Change: For greater clarity
10. Section 8.3 “Duration of Study Period(s) and Subject Participation”
Description of Change: The following sentence was added: “A subject is 
considered enrolled by signing the Informed Consent Form.”
Purpose of Change: For consistency with the information in the Synopsis
For non-commercial use only

BAX 802
Page 106 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
11. Table 5 “Dosing for Perioperative Management” and 
Table 8 “Summary of Required Procedures”
Description of Change: added that the recommended doses are for subjects for 
whom the “GHEA3  [was] not yet performed”
Purpose of Change: For greater clarity and to prevent any ambiguity
12. Section 8.7.3.3.2 “Preoperative and Loading Dose”; 
Section 8.7.3.3.3 “Postoperative Dosing” and Section 10.6 “Rescue Medication”
Description of Change: the following warning was added, “Although peak levels 
above 200% may be achieved, it is recommended that the plasma levels of FVIII 
are not sustained above 200% of normal.” 
Purpose of Change: For clarification of dosing, as recommended by the DSMB.
13. Section 8.7.3.3.3 “Postoperative Dosing” and Section 10.6 “Rescue Medication”
Description of Change: advice was added to increase frequency and /or dose of 
study drug to achieve the recommended FVIII trough levels
Purpose of Change: For greater clarity and to address DSMB concern of 
underdosing with BAX 802 in the postoperative period. 
14. Section 8.7.3.3.3 “Postoperative Dosing” 
Description of Change: recommendation was added on how to proceed with dose 
adjustment when dosing intervals are to frequent to obtain post-dose FVIII level 
results prior to next dosing. 
Purpose of Change: For greater clarity and to address DSMB concern of 
underdosing with BAX 802 in the postoperative period.
15. Section 8.7.3.3.4 “Dosing for Unrelated/Surgical Site Bleeding Episodes during the 
Postoperative Period” 
Description of Change: re-phrased the information regarding follow-up treatment 
with SOC product if subject cannot continue receiving the IP at the study site, or 
subject cannot travel to the site. 
Purpose of Change: For greater clarity.
16. Section 10.4 “Study Periods” and Section 20.1 Procedures per Study Period
Description of Change: the description of the End of Study Visit previously part of 
Section 10.4.1 was made a new distinct Section 10.4.4 “End of Study Visit”
Purpose of Change: For greater clarity
For non-commercial use only

BAX 802
Page 107 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
17. Section 10.4 “Study Periods”, Section 11.2.5 “Hemostatic Efficacy Rating for 
Treatment of Unrelated/Surgical Site Bleeding Episodes” 
Section 11.3 “Factor VIII Activity”, 
Section 20.1 Procedures per Study Period, Table 9 and Table 10
Description of Change: the Discharge Visit Section was renamed “GHEA3 Visit 
and the timing of this visit was re-defined.
Purpose of Change: For greater clarity
18. Section 10.4.4 “End of Study Visit”
Description of Change: Information was added: “The End of Study Visit should be 
performed in ALL subjects who have received at least a dose of BAX 802 during 
Study 241502. This applies also to subjects who receive dose(s) of BAX 802 and 
do not undergo surgery and withdraw from the study AND to subjects who receive 
any rescue medications and subsequently withdraw from the study. “
Purpose of Change: For greater clarity
19. Section 10.5 “Medication and Non-Drug Therapies
Description of Change: precision was added regarding the period during which the 
listed non-permitted medications are not allowed.
Purpose of Change: For greater clarity and to prevent any ambiguity
20. Section 10.6 “Rescue Medications”
Description of Change: additional precisions were added to the recommendation for 
when the use of rescue medication should be considered by the investigator.
Purpose of Change: For greater clarity and to address DSMB concern of 
underdosing with BAX 802 in the postoperative period.
21. Section 10.6 “Rescue Medications” and Table 8, Section 3 and Section 4
Description of Change: the requirement for patients who switched to rescue 
medication to attend the End of Study Visit was added in this section.
Purpose of Change: To align with the definition of End of Study Visit in 
Section 10.4.4
22. Section 11.2.3 Bleeding episodes”, and 
Section 11.2.5 “Hemostatic Efficacy Rating for Treatment of Unrelated/Surgical 
Site Bleeding Episodes”
Description of Change: the definition of “surgical site bleeding episodes” was 
simplified
Purpose of Change: For greater clarity
For non-commercial use only

BAX 802
Page 108 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
23. Section 12.7 Clinical Laboratory Parameters and Table 10
Description of Change: Duplicated information was deleted and a reference to the 
sample sample collection schedule added. 
Purpose of Change: For greater clarity
24. Section 12.8 Vital Signs and Table 9
Description of Change: Additional information was inserted regarding vital sign 
assessment schedule.
Purpose of Change: For greater clarity
25. Section 20.1 Procedures per Study Period
Description of Change: Table 8 was revised to incorporate the changes made to the 
required procedures described in the protocol
Purpose of Change: For consistency with the information in the study protocol body.
26. Section 20.3 “Schedule of Study Procedurals Assessments”
Description of Change: Table 9 was updated to incorporate the revisions related to 
the schedule of study procedures and assessments
Purpose of Change: For consistency with the information in the study protocol body.
27. Section 20.3 “Schedule of Study Procedurals Assessments”
Description of Change: procedures and laboratory assessments for unrelated/surgical 
site bleeding episodes during the postoperative period were presented in a new 
layout in Table 9 and Table 10, respectively.
Purpose of Change: For greater clarity.
For non-commercial use only

BAX 802
Page 109 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX 802) in Subjects with Congenital Hemophilia A with Factor VIII Inhibitors 
Undergoing Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 6: 2017 DEC 14
Replaces: AMENDMENT 4: 2017 JUN 28
OTHER ID(s)
NCT Number: NCT02895945
EudraCT Number: 2015-005521-39
IND NUMBER: BB-IND 014798
By signing below, the Investigator acknowledges that he/she has read and understands 
this protocol, and will comply with the requirements for obtaining informed consent from 
all study subjects prior to initiating any protocol-specific procedures, obtaining written 
initial and ongoing EC(s) protocol review and approval, understands and abides by the 
requirements for maintenance of source documentation, and provides assurance that this 
study will be conducted according to all requirements as defined in this protocol, Clinical 
Trial Agreement, ICH GCP guidelines, and all applicable national and local regulatory 
requirements.
Signature of Principal Investigator
Date
Print Name of Principal Investigator
For non-commercial use only

BAX 802
Page 110 of 110
Clinical Study Protocol Identifier: 241502
2017 DEC 14
BAXALTA CONFIDENTIAL – RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL
INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: BAX 802
STUDY TITLE: A Phase 3, Multicenter, Single-arm, Open-label Study of the 
Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII 
(BAX 802) in Subjects with Congenital Hemophilia A with Factor VIII Inhibitors 
Undergoing Surgical or Other Invasive Procedures
PROTOCOL IDENTIFIER: 241502
CLINICAL TRIAL PHASE 3
AMENDMENT 6: 2017 DEC 14
Replaces: AMENDMENT 4: 2017 JUN 28
OTHER ID(s)
NCT Number: NCT02895945
EudraCT Number: 2015-005521-39
IND NUMBER: BB-IND 014798
By signing below, the Investigator acknowledges that he/she has read and understands 
this protocol, and provides assurance that this study will be conducted according to all 
requirements as defined in this protocol, Clinical Trial Agreement, ICH GCP guidelines, 
and all applicable national and local regulatory requirements.
Signature of Coordinating Investigator
Date
Print Name and Title of Coordinating Investigator
Signature of Sponsor Representative
Date
, MD
, Clinical Programs and Therapeutic Area Head
Baxalta Innovations GmbH
For non-commercial use only