A Phase 3b Continuation Study of the Safety and Efficacy of PEGylated Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in Previously Treated Patients With Severe Hemophilia A
Phase: PHASE3
Conditions: Hemophilia A
Sponsor: Baxalta now part of Shire

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CLINICAL STUDY PROTOCOL
PEGylated rFVIII (BAX 855)
A Phase 3b Continuation study of the Safety and Efficacy of PEGylated 
Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in 
Previously Treated Patients with Severe Hemophilia A
Short Title: Phase 3b Continuation Study of the Safety and Efficacy of Prophylactic 
BAX 855 in PTPs with Severe Hemophilia A
PROTOCOL IDENTIFIER: 261302
CLINICAL TRIAL PHASE 3b
AMENDMENT 1: 2013 OCT 02
Replaces: ORIGINAL: 2013 JUN 18
NCT Number: NCT01945593
EudraCT Number: 2013-002236-24
IND NUMBER: 15299
Study Sponsor(s):
Baxter Healthcare Corporation
One Baxter Way
Westlake Village, CA 91362
Baxter Innovations GmbH
Industriestrasse 67
A-1221 Vienna, AUSTRIA

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1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
Barbara Valenta-Singer, MD
 Clinical Development
Baxter Healthcare Corporation
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.
PPD

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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 
SERIOUS ADVERSE EVENT REPORT (SAER) 
FORM AND TRANSMITTED TO THE SPONSOR 
WITHIN 24 HOURS AFTER BECOMING AWARE OF THE EVENT
See 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:

AE, Section 12.1

SAE, Section 12.2

Assessment of AEs, Section 12.11

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3. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of 
Investigational Product 
(IP)
BAX 855
Name(s) of Active 
Ingredient(s)
PEGylated recombinant factor VIII (PEG-rFVIII)
CLINICAL CONDITION(S)/INDICATION(S)
Previously treated patients (PTPs) with severe hemophilia A (FVIII <1%)
PROTOCOL ID
261302
PROTOCOL TITLE
A Phase 3b Continuation study of the Safety and Efficacy of PEGylated 
Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in 
Previously Treated Patients with Severe Hemophilia A
Short Title
Phase 3b Continuation Study of the Safety and Efficacy of Prophylactic 
BAX 855 in PTPs with Severe Hemophilia A
STUDY PHASE
Phase 3b 
PLANNED STUDY PERIOD
Initiation
2013 OCT
Primary Completion
2016 DEC (100 exposure days [EDs])
Study Completion
2016 DEC (100 EDs)
Duration
The overall duration is approximately 36 months from study initiation to last 
subject last visit. 
STUDY OBJECTIVES AND PURPOSE
Study Purpose

To continue the evaluation of the safety and efficacy of prophylaxis with BAX 855 for the 
prevention and treatment of bleeding episodes in PTPs (children and adults from 0 to 75 years of 
age) with severe hemophilia A.
Primary Objective
The co-primary objectives of the study are:
1.
To determine the safety of BAX 855 based on the incidence of FVIII inhibitory antibody
development
2.
To determine the efficacy of BAX 855 based on the annualized bleed rate (ABR) of spontaneous 
bleeding episodes (episodes not associated with trauma)
Secondary Objective(s)
Efficacy
1.
To determine the total ABR (spontaneous and traumatic bleeding episodes) 
2.
To determine the rate of success of BAX 855 for treatment of breakthrough bleeding episodes
3.
To characterize the success of BAX 855 for treatment of bleeding episodes by the number of 
BAX 855 infusions for treatment and the length of intervals between bleeding episodes
4.
To determine total weight-adjusted consumption of BAX 855 for prophylaxis and for the treatment 
of bleeding episodes
5.
To assess Health-Related Quality of Life (HRQoL) over time for subjects receiving BAX 855

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Safety
1.
To determine the safety of BAX 855, as assessed by the occurrence of AEs and changes in vital 
signs and clinical laboratory parameters 
2.
To determine the immunogenicity of BAX 855
Exploratory Objective

To assess patient satisfaction, patient activity levels, and health resource use over time for subjects 
receiving BAX 855
STUDY DESIGN
Study Type/ 
Classification/ 
Discipline
Safety and Efficacy
Control Type
No Control
Study Indication Type
Prevention and Treatment
Intervention model 
Parallel
Blinding/Masking
Open-label
Study Design
This is a phase 3b, prospective, open label, multi-center study to evaluate the 
safety and efficacy of BAX 855 for prophylactic use in approximately 200 male 
children and adult PTPs (0 to 75 years of age) with severe hemophilia A. The 
study plans to include subjects from other BAX 855 studies and BAX 855-naïve 
subjects. Subjects will receive BAX 855 for prophylaxis based on their previous 
treatment regimen and outcome for at least 100 EDs (as accumulated across all 
BAX 855 studies).
Other BAX 855 studies currently include the phase 2/3 pivotal study (Baxter 
clinical study 261201), surgery study (Baxter clinical study 261204), and 
pediatric PTP study (Baxter clinical study 261202).
Planned Duration of 
Subject Participation
The subject participation period is estimated to be approximately 6 to 36 months. 
All subjects will continue on study until a minimum of 100 EDs per subject has 
been achieved across all BAX 855 studies in which each subject participated. 
Following 100 EDs, subjects will be given the option to continue until the study 
is terminated.
Primary Outcome Measure 
Safety: Development of inhibitory antibodies to FVIII
Efficacy: Spontaneous ABR
Secondary Outcome Measure(s)
Efficacy
1.
Total ABR (spontaneous and traumatic bleeding episodes)
2.
Rate of success of BAX 855 for treatment of breakthrough bleeding episodes
3.
Number of BAX 855 infusions to treat bleeding episodes
4.
Time intervals between bleeding episodes
5.
Weight-adjusted consumption of BAX 855

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Safety 
1.
Occurrence of AEs and SAEs
2.
Changes in vital signs and clinical laboratory parameters (hematology, clinical chemistry, and 
lipids)
3.
Immunogenicity
a.
Binding antibodies (IgG and IgM) to FVIII, BAX 855, and PEG
b.
Anti-CHO antibodies
Patient Reported Outcomes (PROs)
Changes from baseline in the following:
1.
Bleed and pain severity as measured using the Haemo-SYM questionnaire
2.
HRQoL as assessed using the SF-36 questionnaire
Exploratory Outcome Measure(s)
1.
Patient satisfaction with treatment will be assessed using the Satisfaction Question Set
2.
Patient Activity Level
3.
Health resource use data (eg, physician office visits, hospitalizations, length of stay, days missed 
from work/school)
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Investigational 
Product(s) 
BAX 855
Dosage form: BAX 855 is formulated as a sterile, highly purified protein 
preparation in lyophilized form for intravenous (i.v.) infusion and is provided in 
single-dose vials, which may contain nominally 250, 500, 1000, and 2000 IU 
rFVIII/vial, along with a vial of diluent (2 or 5 mL sterile water for injection 
(SWFI) as available).
Dosage frequency: The BAX 855 dosage and infusion frequency for the initial 
prophylaxis period will be based on the subject’s treatment regimen and 
spontaneous ABR (sABR) outcome from previous BAX 855 studies, as follows:
A. Any subject treated on-demand from the phase 2/3 pivotal study with a 
sABR > 0, any subject from the surgery study, and any BAX 855-naïve 
subject will be treated with a fixed dose of 45± 5 IU/kg twice weekly. 
B. Any subject treated on prophylaxis from the phase 2/3 pivotal study, any 
subject from the pediatric PTP study, and any subject from other BAX 855
studies with a sABR > 0 will be treated with 45 to 80 (± 5) IU/kg twice 
weekly.
C. Any subject treated on prophylaxis or on-demand from the phase 2/3 
pivotal study, any subject from the pediatric PTP study, and any subject 
from other BAX 855 studies with a sABR = 0 may be treated with 30 to 80
(± 5) IU/kg every 5 days (q5d). 
After each consecutive 6 months of treatment, the BAX 855 dosage and/or 
frequency of infusions may be adjusted based on the subject’s sABR outcome as 
follows:
A. Subjects achieving a sABR > 0 on a twice weekly dosing schedule will 
continue with 45 to 80 (± 5) IU/kg twice weekly.
B. Subjects achieving a sABR = 0 on a twice weekly dosing schedule may 
switch to 30 to 80 (± 5) IU/kg q5d. 

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C. Subjects achieving a sABR = 0 on a q5d dosing schedule may switch to 30
to 80 (± 5) IU/kg every 7 days (q7d).
D. Subjects achieving a sABR ≤2 on a q5d or a q7d dosing schedule may 
continue on their current infusion frequency.
E. Subjects achieving a 2 < sABR ≤4 on a q7d dosing schedule may switch 
back to 30 to 80 (± 5) IU/kg q5d.
F. Subjects achieving a sABR > 2 on q5d or ABR > 4 on q7d may switch
back to 45 to 80 (± 5) IU/kg twice weekly.
From these recommended dosages and infusion frequencies, the investigator 
will determine the prescribed dosage (allowing ± 5 IU/kg for variation), 
whether or not the q5d or q7d infusion frequency will be employed, and 
whether or not the subject’s regimen will change after each 6 months of 
treatment.
Mode of Administration: intravenous bolus infusion
SUBJECT SELECTION 
Targeted Accrual
Approximately 250 PTP male subjects with severe hemophilia A.
Number of 
Groups/Arms/Cohorts
A single group of BAX 855 prophylaxis
Inclusion Criteria
BAX 855 naïve subjects who are ≥ 12 years of age can only be enrolled in this continuation study after 
enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve subjects who are < 12 years of age and in 
countries where the pediatric PTP study is being conducted can only be enrolled in this continuation study 
after enrollment in the pediatric PTP study is closed.
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subject and/or legal representative has/have voluntarily provided signed informed consent.
2.
Subject is from 0 to 75 years of age at screening.
3.
Subject is male with severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central 
laboratory at screening after at least a 72-hour washout period or a documented FVIII clotting 
activity < 1% (confirmation is only required for BAX 855 naïve subjects).
4.
Subject has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 
150 EDs. 
5.
Subject is currently receiving prophylaxis or on-demand therapy with FVIII.
6.
Subject has a Karnofsky (see Section 20.3) or Lansky performance score of ≥ 60.
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ 
count ≥200 cells/mm3, as confirmed by central laboratory at screening. 
8.
Subject is hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer 
will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic 
stable hepatitis.
9.
Subject is willing and able to comply with the requirements of the protocol.

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Exclusion Criteria
Subjects, those who meet ANY of the following criteria are not eligible for this study:
1.
Subject has detectable FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of 
the Bethesda assay) as confirmed by central laboratory at screening.
2.
Subject has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the 
Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any time prior to screening.
3.
Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A 
(eg, qualitative platelet defect or von Willebrand’s disease).
4.
Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or Tween 80.
5.
Subject has severe chronic hepatic dysfunction [eg, ≥ 5 times upper limit of normal alanine 
aminotransferase (ALT), as confirmed by central laboratory screening, or documented at a local 
laboratory within 6 months prior to screening, or a documented INR > 1.5]
6.
Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central 
laboratory at screening, or documented at a local laboratory within 6 months prior to screening.
7.
Subject has current or recent (< 30 days) use of other PEGylated drugs prior to study participation 
or scheduled use of such drugs during study participation. 
8.
Subject has participated in another clinical study involving an IP other than BAX 855 or device 
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.
9.
Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the 
opinion of the investigator, would affect subject safety or compliance.
10. Subject is a family member or employee of the investigator.
STATISTICAL ANALYSIS
Sample Size Calculation
In total, approximately 250 subjects will be enrolled in this study. This sample size is based on the sample 
size calculations of the other BAX 855 studies (including the phase 2/3 pivotal, surgery, pediatric PTP), as 
well as the guidance EMA/CHMP/BPWP/144533/2009. 
Planned Statistical Analysis
Primary Analysis
The number and proportion (Clopper-Pearson exact 95% CI) of subjects who develop inhibitory antibodies 
to FVIII will be provided. Only the inhibitory antibodies developed after the first exposure to BAX 855 will 
be included in the analysis.
The primary outcome measure, the spontaneous ABR, will be assumed to have a negative binomial 
distribution, and the mean ABR (95% CI) will be estimated using a general estimating equation (GEE) 
model framework (with a logarithmic link function which is the default for the negative binomial 
distribution) with treatment regimen as a fixed effect, subject effect as a random effect, age at baseline as a 
continuous covariate, and the logarithm of follow-up time (in years) as an offset.
Secondary Analyses

The total ABR (spontaneous and traumatic bleedings) will be estimated and similarly described as the 
primary efficacy outcome.

Rate of Success of BAX 855 for treatment of breakthrough bleeding episodes

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Success will be defined as a rating of excellent or good using the efficacy rating scale for treatment of 
bleeding episodes, 24 hours after initiation of BAX 855 treatment for the bleeding episode.
Success proportion (95% CI) will be estimated within a general estimating equation (GEE) model 
framework. The model will account for the fixed effects of bleeding severity, and the random subject effect. 
For the dependent variable (success: yes/no) a binomial distribution and a log link will be assumed, and for 
the subject effect (defined by a repeated statement) an independence correlation structure will be used to 
start the estimation. Estimated model parameter values and CI limits will then be back-transformed to the 
original scale by exponentiation.

Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
Frequency tables will be prepared for the number of infusions required for the treatment of a bleed. 
The median number of infusions (and nonparametric 95% CI) will be estimated. 

Time Intervals Between Bleeding Episodes
The average time interval between 2 consecutive bleeding episodes will be computed for each 
subject. If a subject does not have any bleeding episode then the observation will be censored at the 
end of the follow-up time of the respective subject. The median (95% CI) of those average time 
intervals between 2 bleeding episodes will be estimated.

Weight-Adjusted Consumption of BAX 855
Consumption of BAX 855 will be summarized as average number of BAX 855 infusions and average 
weight-adjusted consumption of BAX 855 per month. 

Haemo-SYM
Higher scores on the Haemo-SYM indicate worse symptom severity. Changes from Baseline to End 
of Treatment in the Haemo-SYM scores will be tested for statistical significance, using a Wilcoxon 
test for paired samples. Improvement in the Haemo-SYM pain subscale of at least 11 points 
decreasing will be considered a meaningful improvement (a 1 point change on each pain question). 
Number and proportion of subjects with meaningful improvement in the Haemo-SYM pain subscale 
will be tabulated. 
SF-36
Lower scores on SF-36 indicate worse HRQoL. Changes from Baseline to End of Treatment in the 
SF-36 scores will be tested for statistical significance using a Wilcoxon test for paired samples. 
Improvement in the SF-36 scale of at least 3 points increasing will be considered a meaningful 
improvement. The number and proportion of subjects with meaningful improvement in SF-36 will be 
tabulated.
Safety Analysis
Frequency counts and percentages will be calculated for SAEs, occurrence of inhibitory and binding 
antibodies, occurrence of severe allergic reactions, and occurrence of thrombotic events. 
AEs that occurred during or after treatment will be presented in summary tables. AEs will be cross-tabulated 
for relatedness, seriousness, and severity. AEs will be categorized according to the MedDRA dictionary and 
summarized by system organ class and preferred term. 
Interim Safety Reviews
The first interim safety review will be done when 35 subjects complete 6 months of BAX 855 treatment with 
30 to 80 IU/kg q5d. 
Descriptive statistics of ABR of this period will be provided, in addition, the number and percentage (95% 
CI) of subjects with ABR = 0 in this 6-month observation period will be provided.

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The second interim safety review will be done when 20 subjects complete 6 months of BAX 855 treatment 
with 30 to 80 IU/kg q7d.
The analysis of this interim will be the same as the first interim safety review.
An additional safety review is planned upon completion of the phase 2/3 pivotal study.

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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 ........................................................................................... 11
5. LIST OF ABBREVIATIONS .................................................................................... 16
6. BACKGROUND INFORMATION .......................................................................... 19
6.1 Description of Investigational Product ............................................................... 19
6.2 Clinical Condition/Indication .............................................................................. 20
6.3 Population To Be Studied..................................................................................... 20
6.4 Findings from Nonclinical and Clinical Studies................................................. 21
6.4.1 Findings from Clinical Studies ..................................................................... 21
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 22
6.6 Compliance Statement.......................................................................................... 22
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 23
7.1 Study Purpose ....................................................................................................... 23
7.2 Primary Objectives............................................................................................... 23
7.3 Secondary Objectives ........................................................................................... 23
7.3.1 Efficacy ........................................................................................................... 23
7.3.2 Safety............................................................................................................... 23
7.4 Exploratory Objectives......................................................................................... 23
8. STUDY DESIGN......................................................................................................... 24
8.1 Brief Summary...................................................................................................... 24
8.2 Overall Study Design............................................................................................ 24
8.3 Duration of Study Period(s) and Subject Participation .................................... 25
8.4 Outcome Measures ............................................................................................... 25
8.4.1 Primary Outcome Measures......................................................................... 25
8.4.1.1 Safety........................................................................................................ 25
8.4.1.2 Efficacy .................................................................................................... 25
8.4.2 Secondary Outcome Measures ..................................................................... 26

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8.4.2.1 Efficacy .................................................................................................... 26
8.4.2.2 Safety........................................................................................................ 26
8.4.2.3 Patient Reported Outcomes................................................................... 26
8.4.3 Exploratory Outcomes Measure .................................................................. 26
8.4.4 Randomization and Blinding........................................................................ 26
8.5 Study Stopping Rules............................................................................................ 26
8.6 Investigational Product(s).................................................................................... 27
8.6.1 Packaging, Labeling, and Storage................................................................ 27
8.6.2 Administration ............................................................................................... 27
8.6.3 Description of Treatment.............................................................................. 28
8.6.3.1 Treatment of Bleeding Episodes............................................................ 31
8.6.3.2 Immune Induction for Inhibitor Development.................................... 32
8.6.4 Treatment for Surgery or Dental Procedures............................................. 33
8.6.5 Investigational Product Accountability ....................................................... 33
8.7 Source Data ........................................................................................................... 34
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 34
9.1 Inclusion Criteria.................................................................................................. 34
9.2 Exclusion Criteria................................................................................................. 35
9.3 Withdrawal and Discontinuation ........................................................................ 36
10. STUDY PROCEDURES .......................................................................................... 37
10.1 Informed Consent and Enrollment ................................................................... 37
10.2 Subject Identification Code................................................................................ 37
10.3 Screening and Study Visits................................................................................. 38
10.3.1 Screening Visit ............................................................................................. 38
10.3.2 Start of Prophylaxis Visit............................................................................ 41
10.3.3 Follow-up Visits (at 6 Weeks and Every 3 Months) ................................. 42
10.3.4 End of Study Visit........................................................................................ 43
10.3.5 Patient Reported Outcomes (PROs) .......................................................... 43
10.4 Medications and Non-Drug Therapies.............................................................. 45
10.5 Subject Diary....................................................................................................... 46
10.6 Subject Completion/Discontinuation ................................................................ 46
10.7 Procedures for Monitoring Subject Compliance............................................. 47
11. ASSESSMENT OF EFFICACY.............................................................................. 47
11.1 Annualized Bleed Rate (ABR) ........................................................................... 47
11.2 Rate of Success of BAX 855 for Treatment of Bleeding Episodes.................. 48
11.3 Number of BAX 855 Infusions Needed for the Treatment of Bleeding 
Episodes ................................................................................................................. 48
11.4 Time Intervals Between Bleeding Episodes...................................................... 48
11.5 Weight-Adjusted Consumption of BAX 855 .................................................... 48

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12. ASSESSMENT OF SAFETY................................................................................... 49
12.1 Adverse Events.................................................................................................... 49
12.2 Serious Adverse Event........................................................................................ 49
12.3 Urgent Safety Measures ..................................................................................... 50
12.4 Non-Serious Adverse Event ............................................................................... 50
12.5 Severity ................................................................................................................ 50
12.6 Causality .............................................................................................................. 51
12.7 Preexisting Diseases ............................................................................................ 52
12.8 Unexpected Adverse Events............................................................................... 52
12.9 Untoward Medical Occurrences........................................................................ 53
12.10 Non-Medical Complaints ................................................................................. 53
12.11 Assessment of Adverse Events......................................................................... 53
12.12 Medical, Medication, and Non-Drug Therapy History................................. 55
12.13 Physical Examinations...................................................................................... 56
12.14 Clinical Laboratory Parameters...................................................................... 56
12.14.1 Hematology, Clinical Chemistry, and Lipid Panel................................. 56
12.14.2 Blood Type.................................................................................................. 57
12.14.3 Factor VIII Activity and Antigen............................................................. 57
12.14.4 Immunogenicity Assays............................................................................. 57
12.14.5 Viral Serology............................................................................................. 58
12.14.6 Assessment of Laboratory Values ............................................................ 58
12.14.6.1 Assessment of Abnormal Laboratory Values................................... 58
12.14.7 Biobanking.................................................................................................. 59
12.15 Vital Signs.......................................................................................................... 59
13. STATISTICS............................................................................................................. 59
13.1 Sample Size and Power Calculations ................................................................ 59
13.2 Datasets and Analysis Cohorts .......................................................................... 60
13.2.1 Safety Analysis Set....................................................................................... 60
13.2.2 Full Analysis Set........................................................................................... 60
13.2.3 Per Protocol Analysis Set............................................................................ 60
13.3 Handling of Missing, Unused, and Spurious Data........................................... 60
13.4 Methods of Analysis............................................................................................ 60
13.4.1 Primary Outcome Measure......................................................................... 60
13.4.1.1 Primary Safety Outcome Measure...................................................... 60
13.4.1.2 Primary Efficacy Outcome Measure .................................................. 60
13.4.2 Secondary Outcome Measures ................................................................... 61
13.4.2.1 Total ABR.............................................................................................. 61
13.4.2.2 Rate of Success of BAX 855 for Treatment of Breakthrough 
Bleeding Episodes ................................................................................... 61
13.4.2.3 Number of BAX 855 Infusions for the Treatment of Bleeding 
Episodes ................................................................................................... 61
13.4.2.4 Time Intervals Between Bleeding Episodes........................................ 61
13.4.2.5 Weight-Adjusted Consumption of BAX 855...................................... 61

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13.4.3 Patient Reported Outcomes........................................................................ 62
13.4.3.1 Haemo-SYM.......................................................................................... 62
13.4.3.2 SF-36 ...................................................................................................... 62
13.4.4 Safety Analysis ............................................................................................. 62
13.4.5 Exploratory Outcome Measures ................................................................ 62
13.5 Planned Interim Safety Review of the Study.................................................... 62
13.5.1 Interim Safety Review 1 .............................................................................. 63
13.5.2 Interim Safety Review 2 .............................................................................. 63
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 63
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 63
15.1 Investigator’s Responsibility.............................................................................. 63
15.1.1 Investigator Report and Final Clinical Study Report.............................. 64
15.2 Training ............................................................................................................... 64
15.3 Monitoring........................................................................................................... 64
15.4 Auditing ............................................................................................................... 64
15.5 Non-Compliance with the Protocol ................................................................... 64
15.6 Laboratory and Reader Standardization ......................................................... 65
16. ETHICS ..................................................................................................................... 65
16.1 Subject Privacy ................................................................................................... 65
16.2 Ethics Committee and Regulatory Authorities................................................ 65
16.3 Informed Consent ............................................................................................... 65
16.4 Data Monitoring Committee.............................................................................. 66
17. DATA HANDLING AND RECORD KEEPING................................................... 66
17.1 Confidentiality Policy ......................................................................................... 66
17.2 Study Documentation and Case Report Forms ............................................... 66
17.3 Document and Data Retention........................................................................... 67
18. FINANCING AND INSURANCE........................................................................... 67
19. PUBLICATION POLICY........................................................................................ 67
20. SUPPLEMENTS....................................................................................................... 68
20.1 Schedule of Study Procedures and Assessments.............................................. 68
20.2 Clinical Laboratory Assessments ...................................................................... 70
20.3 Karnofsky Score.................................................................................................. 72
21. REFERENCES.......................................................................................................... 73

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22. SUMMARY OF CHANGES.................................................................................... 74
Tables
Table 1 BAX 855 Dosage and Infusion Frequency Schedule and Recommended 
Adjustments .............................................................................................................. 29
Table 2 BAX 855 and ADVATE Treatment Guidelines for Bleeding Episodes ............ 32
Table 3 Efficacy Rating Scale for Treatment of Bleeding Episodes at 24 ± 2 Hours 
from the Initiation of Treatment ............................................................................... 32
Table 4 Comparison of End of Study Assessments from the Other BAX 855 Studies 
(Phase 2/3 Pivotal, Surgery, and Pediatric PTP) and Screening Assessments from 
this Continuation Study............................................................................................. 39

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5. LIST OF ABBREVIATIONS
Abbreviation
Definition
ABR
annualized bleed rate
AE
adverse event
ALT
alanine aminotransferase (SGPT)
AST 
aspartate aminotransferase (SGOT)
AUC 
area under the curve
AUC(0-∞)
area under the plasma concentration curve from 0 to infinity
BAX 855
product code name for Baxter’s PEGylated recombinant FVIII (rFVIII)
BU 
Bethesda unit
US CFR 
US Code of Federal Regulations
CHO 
Chinese hamster ovary
CI
confidence interval
CL 
total body clearance 
Cmax 
maximum plasma concentration
(e)CRF 
(electronic) case report form
DI
dose intensification
DMC
data monitoring committee
EC 
ethics committee
ED
exposure day
ELISA
enzyme-linked immunoabsorbent assay
EMA
European Medicines Agency
FAS
full analysis set
FVIII 
factor VIII
GCP 
Good Clinical Practice
GEE
general estimating equation
GLM
general linear model
HAV
hepatitis A virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV 
hepatitis C virus
HCV Ab
hepatitis C virus antibody

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Abbreviation
Definition
HDL
high density lipoprotein
HIV 
human immunodeficiency virus
h
hour(s)
HRQoL
health-related quality of life 
IB
Investigator Brochure
ICH 
International Conference on Harmonisation
ICF
informed consent form
IgA
Immunoglobulin A
IgE
Immunoglobulin E
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IP 
investigational product
ITI
immune tolerance induction
IU 
international unit (s)
INR
international normalized ratio
IR
incremental recovery over time
i.v.
intravenous(ly)
LDL
low density lipoprotein
MedDRA
Medical Dictionary for Regulatory Activities
Mo
Month
MRT 
mean residence time
NMC
non-medical complaint
PCR
polymerase chain reaction
pdFVIII
plasma-derived factor VIII
PEG
polyethylene glycol
PK 
pharmacokinetic(s)
PKFAS
pharmacokinetic full analysis set
PP
per protocol
PRO
patient reported outcomes
PTP
previously treated patient
q5d
Dose every five (5) days
q7d
Dose every seven (7) days
rFVIII
recombinant factor VIII

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Abbreviation
Definition
SAE 
serious adverse event
SAER 
serious adverse event report
SD
standard deviation
SF-36
Short form-36 questionnaire 
SIC
subject identification code
SWFI 
sterile water for injection
T1/2 
half life
Tmax
time to maximum concentration in plasma
US 
United States
VAS
visual analog scale
VLDL
very low density lipoprotein
Vss 
volume of distribution at steady state
VWF
von Willebrand factor

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6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
BAX 855, a novel PEGylated full-length recombinant factor VIII (rFVIII) molecule, is 
intended for use as a long-acting FVIII replacement therapy for prophylaxis and for the 
treatment of bleeding episodes in patients with severe hemophilia A. 
Currently, the management of severe hemophilia A includes on-demand treatment for 
bleeding episodes and/or prophylaxis to prevent bleeding episodes.1; 2 The average half-
life of current FVIII products is in the range of 12-14 h,3; 4 thus, these prophylaxis 
regimens require infusion every other day or every 2-3 days based on the patient’s 
individual pharmacokinetic (PK) profile.5 BAX 855 may improve the treatment of 
hemophilia A by reducing the frequency of prophylaxis infusions while maintaining a 
similar therapeutic benefit to existing FVIII products, thereby improving patient 
convenience, compliance with therapy, and overall health outcomes.
The rFVIII of BAX 855 is identical to the full-length albumin/plasma free manufactured 
octocog alfa known as ADVATE. The product is expressed in Chinese Hamster Ovary 
(CHO). Polyethylene glycol (PEG) chains (20 kDa) are covalently bound to the rFVIII 
protein using a stable linker. The BAX 855 product is reconstituted with sterile water for 
injection (SWFI) and administered intravenously (i.v.) as a solution by bolus infusion. It 
uses the same stabilizing agents (mannitol, trehalose, histidine, and glutathione) as the 
parent rFVIII product (octocog alfa, ADVATE). Comprehensive preclinical studies as 
well as a successfully completed phase 1 study (Baxter clinical study 261101) have 
shown that the PEGylation extends both the in vivo half-life and the measurable 
circulating activity of the product (as determined by chromogenic and 1-stage clotting 
assays). Physiochemical characterization studies demonstrate that the functional activity 
of BAX 855 is comparable to that of ADVATE. Additional details can be found in the 
BAX 855 Investigator Brochure (IB).
The prophylaxis treatment regimens in this continuation study (30 to 80 [± 5] IU/kg, 
twice weekly, every 5 days [q5d], or every 7 days [q7d]) have been developed to ensure 
that subjects maintain FVIII trough levels above 1%. The dosage and frequency of 
infusions are calculated based on the 1.4 to 1.5 fold extended half-life of BAX 855
compared with ADVATE and on FVIII trough level estimated from subjects’ half-life 
and incremental recovery values in the phase 1 study (Baxter clinical study 261101). In 
this continuation study, treatment regimens may be further adjusted at 6-month intervals 
based on the subject’s treatment outcome. In the BAX 855 phase 2/3 pivotal study 
(Baxter clinical study 261201), the pediatric PTP study (Baxter clinical study 261202),

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and in other BAX 855 studies, subjects are treated on prophylaxis at 30 to 80 (± 5) IU/kg 
every 3 to 4 days. For this continuation study, if a subject achieves a spontaneous 
annualized bleed rate (ABR) = 0 in the prior 6 months of treatment, he may receive a 
lower infusion frequency of q5d. If this subject maintains a spontaneous ABR = 0 in 6 
months of dosing q5d, he may receive a further reduced infusion frequency of q7d. The 
actual prescribed dosage and frequency of infusions will be at the discretion of the 
investigator. For BAX 855 naïve subjects, treatment will begin at 45± 5 IU/kg twice 
weekly and after 6 months, the regimen may be adjusted based on treatment outcome.
Subjects who were previously treated on-demand, may receive on-demand treatment 
before the first prophylaxis dose (ie, after screening). The on-demand treatment regimen 
(dosages ranging from 10 to 60 [± 5] IU/kg) is based on extensive previous experience 
from use of ADVATE (additional information can be found in the ADVATE IB). The 
dosing is further supported by preclinical PK and bleeding model studies as well as the 
phase 1 clinical study in subjects with severe hemophilia A, which investigated safety 
and PK following infusion of 30 and 60 IU/kg. The FVIII dosing is also aligned with 
recommendations in the EMA/CHMP/BPWP/144533/2009 guideline.6 Doses as high as 
60 ± 5 IU/kg may be used for the treatment of bleeding episodes based upon experience 
with these doses with ADVATE.
Overall exposure is based on the guideline EMA/CHMP/BPWP/144533/2009 for market 
authorization of FVIII products in which a minimum of 100 exposure days (EDs) in at 
least 200 subjects is recommended.6
6.2 Clinical Condition/Indication 
Hemophilia A is an X-linked recessive, congenital bleeding disorder caused by deficient 
or defective coagulation FVIII. The absence of FVIII leads to 'spontaneous' bleeding 
episodes (occurring primarily in joints, muscles, and less commonly, in soft tissues) and 
to excessive bleeding following trauma or injury. Hemophilia A is currently treated with 
FVIII replacement using either plasma-derived (pdFVIII) or rFVIII concentrates.7; 8
The intended indication for BAX 855 is the treatment and prevention of bleeding in 
subjects with hemophilia A. 
6.3 Population To Be Studied
Approximately 250 male PTP subjects with severe hemophilia A, of any ethnic group, 
from 0 to 75 years of age, will be enrolled to achieve a total of 200 evaluable subjects. 
Each subject will have ≥ 100 EDs with BAX 855, as accumulated across all BAX 855
studies in which the subject participates. 

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Justification for enrollment of pediatric subjects is based on the nonclinical safety 
requirements outlined in the ICH M3 Guideline, Section 12 as well as the ICH E11 
Guideline on clinical investigation of medicinal products in the pediatric population. 
Hemophilia is a serious and potentially life-threatening disease. Pediatric subjects are 
expected to benefit from a full-length rFVIII molecule with an extended half-life. 
Moreover, results from nonclinical repeated toxicology studies, the core safety 
pharmacology package, and the clinical phase 1 study have not raised any safety or 
tolerability concerns. Furthermore, the parent protein molecule ADVATE has been used 
extensively in the entire pediatric population with no unforeseen adverse events (see the
ADVATE IB). Children < 12 years of age will not be enrolled in this continuation study 
until enrollment in the BAX 855 pediatric PTP study has been completed. At least 60 
evaluable subjects in this BAX 855 continuation study must be < 12 years of age.
6.4 Findings from Nonclinical and Clinical Studies
The viral safety of BAX 855 is ensured by the octocog alfa (ADVATE) bulk drug 
substance manufacturing process as any potential risk of contamination with viruses or 
adventitious agents during the subsequent manufacturing steps of BAX 855 has been 
minimized. No substances of animal origin are added throughout the entire 
manufacturing process of BAX 855.
Preclinical studies have demonstrated BAX 855 to have comparable activity and other 
biochemical properties to ADVATE. The expected prolonged FVIII exposure by 
BAX 855 was demonstrated in PK studies with a mean residence time (MRT) longer than 
ADVATE in FVIII knock-out-mice (1.6 fold), rats (1.2 fold) and cynomolgus monkeys 
(1.5 fold). Prolonged efficacy was shown for BAX 855 in comparison to equivalent doses 
of ADVATE in two primary pharmacodynamic models in FVIII knock-out mice.
Additional data from nonclinical studies can be found in the BAX 855 IB.
6.4.1 Findings from Clinical Studies 
A phase 1, first-in-human study (261101) to assess the safety and PK of BAX 855 in 
PTPs from 18 to 65 years of age with severe hemophilia A with ≥ 150 EDs to FVIII 
products was conducted in Europe and Japan. Single dosages of 30 IU/kg and 60 IU//kg 
BAX 855 were compared to the same doses of ADVATE. Subjects were followed for 28 
days after BAX 855 administration for safety, including adverse events (AEs) and 
changes in vital signs, clinical laboratory assessments, and immunogenicity.

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A total of 24 subjects were enrolled; 19 were treated, of which 18 were evaluable for the 
PK analysis. Nine were treated with 30 IU/kg (Cohort 1) and 10 were treated with 60 
IU/kg (Cohort 2) of BAX 855, including 2 subjects from Japan. 
No subjects developed inhibitors to FVIII or binding antibodies to PEG after BAX 855
infusion. There were no thrombosis-associated events or allergic reactions. No deaths or 
other SAEs occurred, and none of the 11 non-serious AEs (all mild or moderate) were 
considered treatment-related. AEs reported following BAX 855 administration included 
vomiting, nasopharyngitis, upper respiratory tract infection, influenza-like illness, 
arthralgia, headache, and localized swelling. No significant treatment-related changes in 
laboratory values or vital signs were recorded. There were no notable differences in the 
type or rate of AEs experienced by subjects after ADVATE infusion versus BAX 855
infusion.
Eighteen subjects (Cohort 1, n=8; Cohort 2, n=10) were evaluable for PK. Based on the 
one-stage clotting assay, the mean T1/2 (h) was longer for BAX 855 than for ADVATE in 
both Cohort 1 (13.60 h vs 9.90 h) and Cohort 2 (16.64 h vs 11.11 h). Other PK 
parameters also supported an improved PK profile for BAX 855 compared to ADVATE. 
Based on these data, BAX 855 appears to be safe and well tolerated after single dose 
administration. The mean T1/2 was 1.4 and 1.5-fold higher for BAX 855 compared to 
ADVATE (Cohorts 1 and 2, respectively), thereby demonstrating prolonged circulation 
of BAX 855 compared to ADVATE. These data support the use of the BAX 855 dosing 
regimens planned in this study. 
Refer to the BAX 855 IB for periodic updates from the other BAX 855 studies.
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Any anticipated risks and benefits associated with administration of BAX 855 are 
described in the BAX 855 IB.
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.

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7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to continue the evaluation of the safety and efficacy of 
BAX 855 for prophylaxis and for the prevention and treatment of bleeding episodes in 
PTPs (children and adults from 0 to 75 years of age) with severe hemophilia A.
7.2 Primary Objectives
The co-primary objectives of the study are:
1.
To determine the safety of BAX 855 based on the incidence of FVIII inhibitory 
antibody development 
2.
To determine the efficacy of BAX 855 based on the ABR of spontaneous 
bleeding episodes (ie, episodes not associated with trauma)
7.3 Secondary Objectives
7.3.1 Efficacy
1.
To determine the total ABR (spontaneous and traumatic bleeding episodes)
2.
To determine the rate of success of BAX 855 for the treatment of breakthrough 
bleeding episodes
3.
To characterize the success of BAX 855 for treatment of bleeding episodes based 
on the number of BAX 855 infusions for the treatment and the length of 
intervals between bleeding episodes
4.
To determine total weight-adjusted consumption for prophylaxis and for the
treatment of bleeding episodes
5.
To assess Health-Related Quality of Life (HRQoL) over time for subjects
receiving BAX 855
7.3.2 Safety
1. To determine the safety of BAX 855, as assessed by the occurrence of AEs and 
changes in vital signs and clinical laboratory parameters 
2. To determine the immunogenicity of BAX 855
7.4 Exploratory Objectives

To assess patient satisfaction, patient activity levels, and health resource use 
over time for subjects receiving BAX 855

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8. STUDY DESIGN
8.1 Brief Summary
This is a phase 3b, prospective, open label, multi-center study to evaluate the safety and 
efficacy of BAX 855 for prophylactic use in approximately 250 male children and adult 
PTPs (0 to 75 years of age) with severe hemophilia A. The study plans to include subjects 
from other BAX 855 studies and BAX 855-naïve subjects. Subjects will receive 
BAX 855 for prophylaxis based on their previous treatment regimen and spontaneous 
ABR outcome for at least 100 EDs (as accumulated across all BAX 855 studies).
8.2 Overall Study Design 
Subjects who complete treatment and assessments in the other BAX 855 studies (phase
2/3 pivotal, surgery, and/or pediatric PTP studies), as well as BAX 855-naïve subjects, 
and who fulfill the inclusion/exclusion criteria will be eligible to participate in this 
continuation study. Approximately 250 male PTPs with severe hemophilia A will be 
enrolled to achieve 200 evaluable subjects. This study was designed to be in compliance 
with EMA/CHMP/BPWP/144533/2009 recommendations for the study of FVIII in 
severe hemophilia A.6
The subject’s hemophilia history, bleeding episode history, and FVIII usage and 
treatment regimen(s) within the previous year will be collected at screening. Results of 
the screening assessments will be used to establish subject’s eligibility for this study and 
may serve as baseline measurements. Subjects transitioning from the other BAX 855
studies may use end of study assessments in their prior study for screening assessments in 
this continuation study.
Once eligibility is established, subjects will receive BAX 855 for in-home prophylaxis 
with the treatment regimen dependent on their previous regimen and spontaneous ABR 
outcome (as described in Section 8.6.3). Subjects will also treat breakthrough bleeding 
episodes with BAX 855. Details on bleeding episodes, the number of infusions used for 
treatment, and the efficacy of treatment (based on a 4-point rating scale; see 
Section 8.6.3.1 and Table 3) will be recorded in an electronic diary (e-diary). If the 
BAX 855 treatment response is inadequate, ADVATE may be used for rescue therapy. 
Subjects will be treated with BAX 855 for a minimum of 100 EDs (accumulated across 
all BAX 855 studies they have participated in). After 100 EDs, subjects will the option to 
continue in this study until the sponsor terminates it.
Subjects will return to the study site at follow-up visits (at 6 weeks and every 
3 months) after the first prophylactic infusion for safety assessments and for review of 

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their e-diaries. Investigators will review e-diaries for untoward events, concomitant 
medications, non-drug therapies, and patient reported outcomes (PROs; see 
Section 10.3.5). Safety assessments performed at the study visit will include 
immunogenicity (inhibitory antibodies for FVIII and binding antibodies for FVIII,
BAX 855, PEG, and CHO), and changes in conditions of the physical examination, vital 
signs, and clinical laboratory assessments (hematology, clinical chemistry, and lipids). 
Subjects who develop a high responder inhibitor (> 5 BU), or who develop a low 
responder inhibitor (≤ 5 BU but ≥ 0.4 BU) that cannot be adequately managed by the 
prescribed prophylaxis regimen with BAX 855 will be discontinued from study.
The sponsor will suspend enrollment and treatment if 2 or more subjects develop 
anaphylaxis after BAX 855 treatment. The sponsor may stop this study at any time. In 
addition, the sponsor may modify the study based on results of the other BAX 855
studies.
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of this continuation study is approximately 36 months from study 
initiation (ie, first subject enrolled by signing informed consent) to study completion (ie, 
last subject last visit). Recruitment will continue until the last subject has completed any 
other BAX 855 study that the sponsor considers as having potential subjects for this
continuation study. 
The initiation date and the completion date will vary for each subject depending on the 
BAX 855 study he participated in or if he is BAX 855 naïve. The subject participation 
period is estimated to be approximately 6 to 36 months and is dependent on the subject 
receiving a minimum of 100 EDs with BAX 855 (as accumulated across all BAX 855 the 
subject has participated in). Following 100 EDs, subjects will be given the option to 
continue until the study is terminated. 
8.4 Outcome Measures
8.4.1 Primary Outcome Measures
8.4.1.1 Safety

Development of inhibitory antibodies to FVIII
8.4.1.2 Efficacy

Spontaneous ABR

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8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy 
1. Total ABR (spontaneous and traumatic bleeding episodes)
2. Rate of success of BAX 855 for treatment of breakthrough bleeding episodes
3. Number of BAX 855 infusions to treat bleeding episodes
4. Time intervals between bleeding episodes
5. Weight-adjusted consumption of BAX 855
8.4.2.2 Safety
1. Occurrence of AEs and SAEs
2. Changes in vital signs and clinical laboratory parameters (hematology, clinical 
chemistry, and lipids)
3. Immunogenicity (a 72-hour washout period is required)
a.
Binding antibodies (IgG and IgM) to FVIII, BAX 855, and PEG
b. Anti-CHO antibodies
8.4.2.3 Patient Reported Outcomes
Changes from baseline in the following:
1. Bleed and pain severity as measured using the Haemo-SYM questionnaire
2. HRQoL as assessed using the SF-36 questionnaire
8.4.3 Exploratory Outcomes Measure
1. Patient satisfaction with treatment will be assessed using the Satisfaction Question 
Set
2. Patient Activity Level
3. Health resource use data (eg, physician office visits, hospitalizations, length of 
stay, days missed from work/school)
8.4.4 Randomization and Blinding
This is an non-randomized, open-label, concurrent, active treatment clinical study. 
8.5 Study Stopping Rules 
Enrollment and treatment in this continuation study will be suspended or stopped, if the 
following criterion is met:
If 2 or more subjects develop anaphylaxis following exposure to BAX 855

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The study may be terminated, if one or more of the following criteria are met:
The sponsor decides to terminate the study based upon its own assessment of 
safety
The sponsor decides to terminate the study for administrative reasons
8.6 Investigational Product(s)
8.6.1 Packaging, Labeling, and Storage
BAX 855 is formulated as a sterile, highly purified protein preparation in lyophilized 
form for i.v. infusion and is provided in single-dose vials along with a vial of diluent (2 
or 5 mL SWFI, as available). A butterfly transfer set with luer-lock syringes and a 
needleless transfer device will be used for reconstitution and bolus i.v. delivery 
(BAXJECT II high-flow [HF] and BAXJECT III, as available). The BAXJECT system is 
a needleless liquid transfer device with the primary function of transferring diluent from 
its vial into an evacuated vial containing product requiring reconstitution prior to 
infusion. 
A minimum of 4 lots of BAX 855 manufactured for this study will be used. Four nominal 
potencies of BAX 855 will be used, depending upon availability: 250, 500, 1,000 and 
2,000 IU/vial. 
The recommended storage condition for BAX 855 is 2°C to 8°C (36°F to 46°F) and it 
should not be allowed to freeze. BAX 855 should be stored and protected from light. The 
reconstituted product should ideally be used immediately but no longer than 3 hours after 
reconstitution.
For additional information, such as reconstitution instructions, refer to the BAX 855 IB 
and/or other specific instructions provided by the sponsor. 
8.6.2 Administration
Following reconstitution, BAX 855 should be administered using plastic syringes 
provided by the sponsor since proteins such as BAX 855 may adhere to the surface of 
glass syringes. BAX 855 will be administered i.v., using an appropriately sized syringe, 
as a bolus infusion over a period of ≤5 minutes with a maximum infusion rate of 
10 mL/min, as described in the BAX 855 IB. The reconstituted BAX 855 must be 
administered at room temperature and within 3 hours.

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8.6.3 Description of Treatment
Subjects will be treated on specified prophylaxis treatment regimens for 6-month periods 
until they reach 100 EDs (accumulated across all studies). The BAX 855 regimen (dosage 
and frequency of infusions) will be determined based on the subject’s previous treatment 
regimen and spontaneous ABR (sABR) outcome as follows (also refer to Table 1):
A. Any subject treated on-demand from the phase 2/3 pivotal study with a sABR > 0, 
any subject from the surgery study, and any BAX 855-naïve subject will be 
treated with a fixed dose of 45± 5 IU/kg twice weekly.
B. Any subject treated on prophylaxis from the phase 2/3 pivotal study, any subject 
from pediatric PTP study, and any subject from other BAX 855 studies with an 
sABR > 0 will be treated with 45 to 80 (± 5) IU/kg twice weekly. The investigator 
will determine prescribed dosage with a ± 5 IU/kg allowance.
C. Any subject treated on prophylaxis or on-demand from the phase 2/3 pivotal 
study, any subject from the pediatric PTP study, and any subject from other 
BAX 855 studies with an sABR = 0, may be treated, at the investigator’s 
discretion, with 30 to 80 (± 5) IU/kg q5d. The investigator will determine 
prescribed dosage with a ± 5 IU/kg allowance.
After each consecutive 6 months of treatment, the BAX 855 dosage and/or frequency of 
infusions may be adjusted based on the subject’s estimated sABR for the previous period
as follows (also refer to Table 1): 
A. Subjects achieving a sABR > 0 on a twice weekly dosing schedule will continue 
with 45 to 80 (± 5) IU/kg twice weekly.
B. Subjects achieving aABR = 0 on a twice weekly dosing schedule may switch to 
30 to 80 (± 5) IU/kg q5d, at the investigator’s discretion. 
C. Subjects achieving a sABR = 0 on a q5d dosing schedule may switch to 30 to 80 
(± 5) IU/kg q7d, at the investigator’s discretion.
D. Subjects achieving a sABR ≤2 on a q5d or a q7d dosing schedule may continue
on their current dosage and infusion frequency, at the investigator’s discretion.
E. Subjects achieving a 2 < sABR ≤4 on a q7d dosing schedule may switch back to 
30 to 80 (± 5) IU/kg q5d, at the investigator’s discretion.
F. Subjects achieving an sABR > 2 on q5d or ABR > 4 on q7d may switch back to 
45 to 80 (± 5) IU/kg twice weekly, at the investigator’s discretion.
From these recommended dosages and infusion frequencies, the investigator will 
determine the prescribed dosage (allowing ± 5 IU/kg for variation), whether or not the 

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q5d or q7d infusion frequency will be employed, and whether or not the subject’s 
regimen will change after each 6 months of treatment.
Table 1
BAX 855 Dosage and Infusion Frequency Schedule and Recommended Adjustments
Subjects
0-6 Months
6-12 Months
12-18 Months
≥18 Months
Subjects 
treated on-
demand 
subjects from 
the phase 2/3 
pivotal with 
sABR > 0 
Subjects from 
the surgery 
study
BAX 855
naïve 
subjects
Fixed dose:
45 ± 5 IU/kg 
twice weekly
sABR > 0: 
45 to 80 (± 5) IU/kga
twice weekly
sABR > 0: 
45 to 80 (± 5) IU/kga
twice weekly
sABR > 0: 
45 to 80 (± 5)
IU/kga
twice weekly
sABR = 0: 
30 to 80 (± 5) IU/kga
q5db
sABR > 2: 
45 to 80 (± 5) IU/kga
twice weekly
sABR ≤2: 
30 to 80 (± 5) IU/kga
q5db
sABR = 0: 
30 to 80 (± 5) IU/kga
q7db
sABR > 4: 
45 to 80 (± 5)
IU/kga
twice weekly
2 < sABR ≤4: 
30 to 80 (± 5)
IU/kga
q5db
sABR ≤2: 
30 to 80 (± 5)
IU/kga
q7db

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Table 1
BAX 855 Dosage and Infusion Frequency Schedule and Recommended Adjustments
Subjects
0-6 Months
6-12 Months
12-18 Months
≥18 Months
Subjects from 
the phase 2/3 
pivotal study
Subjects from 
the, pediatric 
PTP study
Subjects from
other 
BAX 855
studies
sABR > 0: 
45 to 80 (± 5)
IU/kga
twice weekly
sABR > 0: 
45 to 80 (± 5) IU/kga
twice weekly
sABR > 0: 
45 to 80 (± 5) IU/kga
twice weekly
sABR > 0: 
45 to 80 (± 5)
IU/kga
twice weekly
sABR = 0: 
30 to 80 (±5) IU/kga
q5db
sABR > 2: 
45 to 80 (± 5) IU/kga
twice weekly
sABR ≤2: 
30 to 80 (± 5) IU/kga
q5db
sABR = 0: 
30 to 80 (± 5) IU/kga
q7db
sABR > 4: 
45 to 80 (± 5) IU/kga
twice weekly
2 < sABR ≤4: 
30 to 80 (± 5) IU/kga
q5db
sABR ≤2: 
30 to 80 (± 5) IU/kga
q7db
Abbreviations: sABR = spontaneous annualized bleed rate; PTP = previously treated patients; q5d = every 
5 days; q7d = every 7 days.
a
From the recommended dosage range, the investigator will determine prescribed dosage, allowing ± 5 
IU/kg.
b
Infusion frequencies of q5d or q7d will be at investigators discretion.
A subject may receive a BAX 855 dosage < 45 IU/kg if he has a known PK profile from 
another BAX 855 study that will maintain his FVIII trough level above 1%. 
For subjects receiving twice weekly prophylaxis and with spontaneous ABR > 2, dosing 
of BAX 855 may, for a 6-month period target, a FVIII trough level of up to 10%, at 
investigators’ discretion and with approval by the sponsor’s medical director. 
Subjects meeting any of the following criteria during prophylaxis may have their 
BAX 855 dosage and/or infusion frequency increased before completion of the 6-month 
treatment period:

Two or more spontaneous (not trauma-related) bleeding episodes in the same
target joint within any 2-month period 

One or more spontaneous (not trauma-related) bleeding episodes in a non-
target joint within any 2-month period

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
FVIII trough level < 1% and investigator’s estimate that the subject has an 
increased risk of bleeding 
The dose adjustment may take place only after consultation with the sponsor’s medical 
director and written documentation of the decision, which will be recorded in the eCRF. 
The BAX 855 dosage may be increased gradually up to a maximum of 80 ± 5 IU/kg 
and/or the frequency of infusions can be changed to twice weekly.
8.6.3.1 Treatment of Bleeding Episodes
BAX 855 will be used for the treatment of bleeding episodes (ie, breakthrough bleeding 
episodes during prophylaxis), according to the guidelines outlined in Table 2. These 
guidelines may be adjusted (ie, below 10 [± 5] IU/kg or above 60 [± 5] IU/kg) by the 
investigator based upon his or her clinical judgment and the severity of the bleeding 
episode (see Table 2). The subject or their caregiver will rate the severity (mild, 
moderate, or severe) of the bleeding episode and will rate the overall treatment response 
at 24 hours (± 2 hours) after initiating treatment. A 4-point efficacy rating scale (Table 3) 
will be used to assess the efficacy of BAX 855 treatment. Efficacy will not be assessed if 
ADVATE or any other FVIII concentrate is administered for the treatment of bleeding 
episodes. Efficacious treatment will be defined as a response of good or excellent. As 
described in Table 3, multiple infusions of BAX 855 may be administered for the 
treatment of a bleeding episode. 
When bleeding is controlled, additional infusions of BAX 855 to maintain hemostasis 
(FVIII trough levels of 1%) is permitted, if required, for a maximum of 24 hours after 
resolution of bleeding or the subject can return to his prophylaxis regimen. Infusions to 
maintain hemostasis will count as EDs.

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Table 2
BAX 855 and ADVATE Treatment Guidelines for Bleeding Episodes
Type of Bleeding Episode
Dose
Frequency of Dosing
Minor
Early hemarthrosis, mild muscle 
bleeding, or mild oral bleeding, 
including, epistaxis
10 to 20 (±5) IU/kg
Repeat infusions every 12 to 24 h for 1 to 
3 days until the bleeding episode is 
resolved
Moderate
Moderate bleeding into muscles, 
bleeding into the oral cavity, definite 
hemarthroses, and known trauma
15 to 30 (±5) IU/kg
Repeat infusions every 12 to 24 h for 
3 days or more until the pain and moderate 
disability/incapacity are resolved
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
30 to 60 (±5) IU/kg
Repeat infusions every 8 to 12 h until the 
bleeding episode is resolved
NOTE: Subjects with life-threatening or gastrointestinal bleeding should be withdrawn from the study.
Table 3
Efficacy Rating Scale for Treatment of Bleeding Episodes 
at 24 ± 2 Hours from the Initiation of Treatment
Excellent
Full relief of pain and 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
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.
8.6.3.2 Immune Induction for Inhibitor Development
Subjects who develop a confirmed (ie, 2 separate assessments within a 2 to 4 week period 
from the central laboratory) high responder inhibitor (> 5 BU) or low responder inhibitor 
(≤ 5 BU but ≥ 0.4 BU) that cannot be adequately managed by the protocol-required 
prophylactic regimen with BAX 855 will be discontinued from this continuation study. 

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The decision to initiate ITI will be made by the subject’s physician, and may be discussed 
with the sponsor’s medical director prior to initiation. The regimen used for ITI will be 
determined by the treating physician but must be approved by the sponsor’s medical 
director.
8.6.4 Treatment for Surgery or Dental Procedures 
Subjects enrolled in this continuation study who require elective surgery may be eligible 
to enroll in the BAX 855 surgery study (Baxter clinical study 261204) if it is open for 
enrollment. Following an invasive or surgical procedure and completion of the surgery 
study, subjects may be eligible to return to this continuation study when they are able to 
resume a prophylaxis regimen and with the sponsor’s medical director approval. Upon 
return to this study, these subjects will receive the treatment regimen corresponding to the 
beginning of the study (45 to 80 [± 5] IU/kg twice weekly for 6 months). 
Subjects from this continuation study who participate in the surgery study will continue 
to receive their continuation study BAX 855 treatment during the following periods in the 
surgery study: 
1. From the screening visit to the pre-surgical PK assessment, 
2. From completion of the pre-surgical PK assessment to initiation of the pre-
operative procedures, and
3. From hospital discharge following the surgery to the end of study visit. 
During these periods, subjects will maintain their e-diaries for the continuation study, the 
continuation study investigator will be responsible for the subject’s safety and treatment,
and any data collected will be part of this continuation study.
During the pre-surgery PK assessment and from the initiation of the pre-operative 
procedures to the end of the surgery study’s treatment plan, subjects will receive 
BAX 855 from the surgery study, and any data collected will be part of the surgery study. 
Subjects who require any emergency surgery will be withdrawn from this continuation 
study.
8.6.5 Investigational Product Accountability
The investigator will ensure that the IP 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, was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received and 

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disposition. IP must be dispensed only at the study site or other suitable location (e.g. 
infusion center; home, as applicable per study design), as specified in the protocol. 
Records will be maintained that includes the subject identification code (SIC), 
dispensation date, and amount dispensed. All remaining partially used and/or unused IP 
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 is to be destroyed, the investigator 
will provide documentation in accordance with sponsor’s specifications.
8.7 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, 
subjects' diaries or evaluation checklists, outcomes reported by subjects, 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 refer to Section 17.2. The 
use of subject diaries is described in Section 10.5.
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects from other BAX 855 studies can be provided with the continuation study 
informed consent form (ICF) prior to the end of study visit to review and consider 
participation in this continuation study. These subjects will complete any additional 
screening assessments within 2 weeks of the previous study’s end of study visit and will 
return to the study site within 6 weeks of the previous study end of study visit to confirm 
eligibility for this continuation study. 
BAX 855 naïve subjects who are ≥12 years of age can only be enrolled in this
continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855
naïve subjects who are < 12 years of age and in countries where the pediatric PTP study 

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is being conducted can only be enrolled in this continuation study after enrollment in the 
pediatric PTP study is closed.
Subjects who meet ALL of the following criteria are eligible for this study:
1. Subject and/or legal representative has/have voluntarily provided signed informed 
consent.
2. Subject is from 0 to 75 years of age at screening.
3.
Subject is male with severe hemophilia A (FVIII clotting activity < 1%) as 
confirmed by central laboratory at screening (after at least a 72-hour washout 
period) or a documented FVIII clotting activity <1% (confirmation is only 
required for BAX 855 naïve subjects).
4.
Subject has documented previous treatment with pd FVIII or rFVIII concentrates 
for ≥150 EDs. 
5.
Subject is currently receiving prophylaxis or on-demand therapy with FVIII.
6.
Subject has a Karnofsky (see Section 20.3) or Lansky performance score of ≥ 60.
7.
Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable 
disease and CD4+ count ≥ 200 cells/mm3, as confirmed by central laboratory at 
screening. 
8.
Subject is hepatitis C virus negative (HCV-) by antibody or PCR testing (if 
positive, antibody titer will be confirmed by PCR), as confirmed by central 
laboratory at screening; or HCV+ with chronic stable hepatitis.
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.
Subject has detectable FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen 
modification of the Bethesda assay) as confirmed by central laboratory at 
screening.
2.
Subject has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen 
modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any 
time prior to screening.
3.
Subject has been diagnosed with an inherited or acquired hemostatic defect other 
than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease).
4.
Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or 
Tween 80.

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5.
Subject has severe chronic hepatic dysfunction [eg, ≥ 5 times upper limit of 
normal alanine aminotransferase (ALT), as confirmed by central laboratory at 
screening, or documented at a local laboratory within 6 months prior to 
screening, or a documented INR > 1.5].
6.
Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as 
confirmed by central laboratory at screening, or documented at a local laboratory 
within 6 months prior to screening.
7.
Subject has current or recent (< 30 days) use of other PEGylated drugs prior to 
study participation or scheduled use of such drugs during study participation. 
8.
Subject has participated in another clinical study involving an investigational 
product (IP) other than BAX 855 or device 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.
9.
Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol 
use that, in the opinion of the investigator, would affect subject safety or 
compliance.
10. 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 end of study visit 
(including in cases of withdrawal or discontinuation) are described in Section 10.3.4.
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 may be withdrawn from treatment or discontinue from further study 
participation for the following reasons:

The subject develops a confirmed high responder inhibitory antibody to FVIII 
(> 5 BU by Nijmegen modification of the Bethesda assay) or a low responder 
inhibitory antibody (≤ 5 BU but ≥ 0.4 BU) that cannot be managed by the 
protocol-required treatment.

The subject experiences a severe anaphylactic reaction to BAX 855.

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
The subject requires therapy with another PEGylated product (eg, PEG-
Interferon).

The subject frequently misses administration of IP (ie, misses more than 30% of 
planned prophylactic doses within any 3-month period). 

The subject is non-compliant with study procedures, in the opinion of the 
investigator. 

The subject repeatedly uses another FVIII therapy for prophylaxis (in the 
absence of an acceptable justification to the sponsor) or for the treatment of 
bleeding episodes. 

The subject requires a surgical or dental procedure and is not eligible or does 
not consent for the surgery study, or participates in the surgery study and then 
refuses to resume participation in this continuation study. If the surgery study is 
closed, the subject will be withdrawn from the continuation study.

The subject experiences a life-threatening bleeding episode (eg, any 
gastrointestinal hemorrhage or intracranial hemorrhage).

The subject experiences severe trauma or requires emergency surgery with
extensive FVIII replacement therapy.
10. STUDY PROCEDURES
10.1 Informed Consent and Enrollment
Any patient who provides informed consent (ie, signs and dates the ICF 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 (eg, 261203) 
to be provided by the sponsor, a 3-digit number study site number (eg, 002) 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 002 will be identified as Subject 261203-
002003. 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.

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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 ICF, new SIC and new CRF are required for that subject.
The procedures to be performed at each study visit, including screening, can be found in 
Supplement 20, Schedule of Study Procedures and Assessments, and Supplement 20.2, 
Clinical Laboratory Assessments. 
Subjects will participate in each of the following study visits:

Screening visit (exception: subjects transitioning from other BAX 855 studies 
who have completed end of study assessments that match assessments required 
for this continuation study screening visit; see Section 10.3.1 for details)

Start of prophylaxis visit

Follow-up visits at the study site at 6 weeks (- 1 or + 2 weeks) and every 3 
months (± 4 weeks) after the start of prophylaxis

End of study visit
10.3.1 Screening Visit
The screening visit procedures, including laboratory assessments, must be completed 
within 45 days prior to the first infusion of BAX 855, or repeated if more than 45 days 
have elapsed. 
Subjects transitioning from the phase 2/3 pivotal, surgery, pediatric PTP, or another 
BAX 855 study, can use the end of study assessments in their prior study for screening 
visit assessments in this continuation study. Any additional required screening 
assessments will be performed at the screening visit in this continuation study within 2 
weeks of completion of the previous study. Subjects will return to the study site no later 
than 6 weeks after the end of study visit in their prior study to confirm eligibility.
Subjects treated only with BAX 855 during the 4 weeks prior to the screening visit will 
be supplied with BAX 855 for a maximum of 6 weeks for prophylaxis treatment based on 
their previous treatment regimen and ABR outcome as described in Section 8.6.3.

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Subjects using FVIII concentrates other than BAX 855 during the 4 weeks prior to the 
screening visit, will be offered ADVATE (to continue their treatment of bleeding 
episodes and prophylaxis) until the start of prophylaxis visit.
As a guideline of the screening assessments, Table 4 compares the end of study
assessments from the other BAX 855 studies with assessments in this continuation study.
Table 4
Comparison of End of Study Assessments from the Other BAX 855 Studies (Phase 2/3 Pivotal, 
Surgery, and Pediatric PTP) and Screening Assessments from this Continuation Study
Assessment
Other BAX 855 Studies
End of Study Assessments
Continuation Study
Screening Assessments
Informed consent
X
Eligibility criteria
X
Medical historya
X
Medication historya
X
Concomitant medicationsa
X
X
Non-drug therapies
X
X
Physical examinationa
X
X
Vital signsa
X
X
Adverse events
X
X
On study bleeding episodes and 
their treatmentb
X
Bleeding episodes and their 
treatmenta
Xa
X
Hematologya
X
X
Clinical chemistrya
X
X
Lipid Panela
X
X
Immunogenicity assaysc
X
X
FVIII/VWF assays 
Xd
Xe
Viral serologya
Xf
X
Blood groupg
X
Patient e-diarya
X
a
Refer to Section 20 and Section 20.2 for more details. It is not necessary to repeat assessments at this 
continuation study screening visit if they are completed at the end of study visit in another BAX 855
study.
b
Record of bleeding episodes and their treatment since last study visit in the prior BAX 855 study.
c
Immunogenicity assessments include: inhibitory antibodies to FVIII, binding antibodies to FVIII, 
BAX 855 and PEG, and anti-CHO antibodies. Both IgG and IgM binding antibodies are measured. A 
72-hour washout period is required.

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d
FVIII/VWF assays include: 1-stage clotting FVIII activity, FVIII chromogenic activity, FVIII antigen,
and VWF antigen at pre-infusion time points only.
e
FVIII assays (only) include 1-stage clotting FVIII activity, FVIII chromogenic activity, and 
FVIII antigen.
f
Performed at the end of study visit in the surgery study.
g
Blood group (A, B, AB or O) if historical data not available.
For BAX 855 naïve patients, the following screening assessments will be performed after 
at least a 72-hour washout: 

Assessment of inclusion/exclusion criteria

Clinical assessments:
Medical history
Hemophilia history, including, 
o
Confirmation of diagnosis and severity
o
Family history of hemophilia
o
Documentation of mutation, if known 
o
The presence of any target joints will be documented. A target 
joint is defined as any single joint (ankles, knees, hips, or elbows) 
with ≥ 3 spontaneous bleeding episodes in any consecutive 6 
month period. 
Bleeding history and treatment
All FVIII replacement therapies used within the last year will be 
documented, including:
o
FVIII regimen (prophylaxis or on-demand) 
o
Product name (or IP name and manufacturer, if applicable) 
o
Dose (for prophylaxis, if applicable, and for treatment of bleeding 
episodes) 
o
Frequency of administration (for prophylaxis)
o
Estimate of average number of infusions for each bleeding episode
o
Usual response to treatment for bleeding episodes
o
Assessment of subject’s ABR over prior 3-6 months, based on 
subject’s own diary or recall
Concomitant medications for last 30 days, and any prior history of use 
of any PEGylated medication (eg, PEG-interferon) at any time in the 
past, including treatment indication, date of last administration, and 
duration of treatment(s), if known
Current non-drug therapies
Physical exam including height (cm) (for subjects less than 18 years of 
age at enrollment) and weight (kg) 

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Vital signs (body temperature (C), respiratory rate (breaths/min), 
pulse rate (beats/min), and systolic and diastolic blood pressure 
(mmHg). 

Laboratory Assessments: 
FVIII assays: 
o
FVIII activity 

1-stage clotting assay 

Chromogenic assay
o
FVIII antigen 
Immunogenicity tests (a 72-hour washout period is required): 
o
Inhibitory antibodies to FVIII (Nijmegen assay)
o
Binding antibodies (IgG and IgM) to FVIII, BAX 855, 
PEG
o
Anti-CHO antibodies
Hematology, clinical chemistry, and lipid panel
Blood group (A, B, AB or O) if historical data not available; if 
available, historical data will be recorded on the CRF.
Viral serology, including:
o
HIV: HIV-1 and HIV-2 Ab
o
HBV: HBsAg, HBsAb, HBcAb
o
HCV: HCVAb

E-diary distribution 
Any positive viral serology test will be confirmed at the central laboratory with a new 
blood sample. HCV titer will be measured by PCR for subjects that are HCV positive.
10.3.2 Start of Prophylaxis Visit
At the start of prophylaxis visit, baseline assessments will be preformed prior to the first 
prophylactic dose of BAX 855. However, subjects transitioning from other BAX 855
studies who receive the first infusion BAX 855 at the screening visit will not have a start 
of prophylaxis visit.
The following baseline assessments will be completed up to 7 days before the first 
infusion of BAX 855 and with at least a 72-hour washout:

Physical examination, including height (for subjects < 18 years of age at 
enrollment) and weight and vital signs 

Hematology, clinical chemistry, and lipid panel

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
FVIII assays 

Immunogenicity assays (a 72-hour washout period is required)

AEs occurring between screening and start of prophylaxis visit 

Concomitant medications

Non-drug therapies

All bleeding episodes and their treatment between screening and start of 
prophylaxis visit 

Patient Reported Outcomes (PROs; as described in Section 10.3.5)

Review of subject’s diary
10.3.3 Follow-up Visits (at 6 Weeks and Every 3 Months) 
Follow-up visits will be performed at 6 weeks (- 1 or + 2 weeks) and every 3 months (± 4 
weeks) after the start of prophylaxis. The follow-up visits must be scheduled so that 
blood sampling is prior to planned the BAX 855 infusion in order for the FVIII 
measurements to be used as an estimate of FVIII trough level and FVIII peak level is 30
± 15 minutes after the BAX 855 infusion. The following assessments will be performed
after at least a 72-hour washout:

Physical examination, including height (for subjects less than 18 years of age at 
enrollment), weight, and vital signs

Hematology, chemistry chemistry, and lipid panel

FVIII assays: blood sampling before and 30 ± 15 minutes after the BAX 855
infusion

Immunogenicity assays (a 72-hour washout period is required)

Continuous monitoring for AEs and Concomitant medications 

Non-drug therapies

All bleeding episodes and their treatment from first prophylaxis dose of 
BAX 855 will be documented

Review of subject’s diary

At each consecutive 6 months visit, the ABR must be estimated and dose 
regimen may be revised (refer to Section 8.6.3)

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10.3.4 End of Study Visit
The following end of study visit assessments will be performed 28 days ± 2 weeks after 
the last infusion of BAX 855 and at least a 72-hour washout:

Physical examination including height (for subjects less than 18 years of age at 
enrollment), weight, and vital signs

Non-drug therapies

Hematology, chemistry, lipid panel

FVIII assays

Immunogenicity assays (a 72-hour washout period is required)

Continuous monitoring for AEs and concomitant medications

All bleeding episodes and their treatment from last dose of BAX 855 until study 
termination 

PROs (as described in Section 10.3.5)

Review of subject’s diary
10.3.5 Patient Reported Outcomes (PROs)
PROs will be administered at the start of prophylaxis visit (baseline) and end of study 
visit. Some questionnaires may not be administered in all participating countries due to 
the unavailability of linguistically validated translations for certain PRO measures in 
some countries. In addition, subjects who are younger than the minimal age limit required 
for these assessments will not complete the assessments.
The following PROs will be assessed at the start of prophylaxis and end of study visits: 

Bleed and pain severity will be measured using the Haemo-SYM for subjects 
≥18 years of age

HRQoL will be assessed using the SF-36 for subjects ≥ 14 years of age

Patient satisfaction with treatment will be assessed using the Satisfaction 
Questionnaire (for subjects ≥12 years of age, the subject completes the 
questionnaire; for subjects < 12 years of age, the caregiver completes it on 
behalf of the subject)

Patient Activity Level (for subjects ≥ 12 years of age, the subject completes the 
assessment; for subjects < 12 years of age, the caregiver completes it on behalf 
of the subject)

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Details on each of the PROs are as follows:

Haemo-SYM Questionnaire – This is a self-administered, validated 
questionnaire designed to assess symptom severity in patients with hemophilia. 
This measure contains 17 items and includes 2 domains: Bleeds and Pain. Scores 
for each of these 2 domains can be calculated, with higher scores indicating more 
severe symptoms. This questionnaire will be administered only to subjects ≥18
years of age at enrollment)

Short Form-36 (SF-36) – The SF-36 is a self-administered, validated 
questionnaire designed to measure generic HRQoL. This 36-item questionnaire 
measures 8 domains, including: Physical functioning, Role-physical, Bodily pain, 
General health, Vitality, Social functioning, Role emotional, and Mental health. 
Two summary scores can be calculated, the Physical Component Score, and the 
Mental Component Score. Additionally, scores can be calculated for each of the 8 
domains. Higher scores indicate better health status. This questionnaire will be 
administered only to subjects ≥14 years of age and 

Patient Satisfaction Questionnaire – This questionnaire is a non-validated 
measure that assesses the subject’s (or via their caregiver) level of satisfaction 
with their treatment. For BAX 855 naïve subjects and BAX 855 naïve surgery 
subjects, at the end of study visit, the questionnaire also assesses the subject’s 
preference between his previous treatment prior to the study and BAX 855. This 
questionnaire will be administered to all age groups. For subjects ≥12 years of 
age at enrollment, the subject completes the questionnaire and for subjects < 12
years of age at enrollment, the caregiver completes it on behalf of the subject.

Patient Activity Level – Subjects will also be asked to estimate their activity 
levels. This will consist of a few questions asking subjects (or their caregiver) to 
rate their current level of activity. These data will be collected for all age groups. 
For subjects ≥12 year of age at enrollment, the subject completes the assessment 
and for subjects < 12 years of age at enrollment, the caregiver completes it on 
behalf of the subject.
In addition, the following will be collected where applicable, for each occurrence:

Health Resource Use – The subject (or their caregiver) will record the following 
events: days missed from work/school (as appropriate) and days not able to 
perform normal activities outside of work/school due to hemophilia, physician 
office visits, hemophilia treatment site visits, emergency room visits (reason and 
number), hospitalizations (reason, dates of hospitalization and associated length 
of stay). These data will be collected for all age groups.

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10.4 Medications and Non-Drug Therapies 
The following medications are not permitted within 30 days before study entry and 
during the course of the study:

Any PEGylated medication (eg, PEG-interferon)

Any investigational drug, biologic, or device

Any FVIII other than BAX 855 or ADVATE (during the course of 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 before study entry and 
during the course of the study:

Medications:
ADVATE, provided by the study site, is permitted for:
o
Treatment of bleeding episodes and prophylaxis following 
enrollment until first prophylactic dose of BAX 855
o
During the observation period between the last follow-up 
visit and end of study visit
o
Rescue therapy for bleeding episodes that do not respond to 
BAX 855 during the study 
o
Any ADVATE taken, regardless of whether it is provided 
by the study site or not, will be documented.
Hemostatic agents, such as tranexamic acid, are permitted, as indicated 
by the subject’s treating physician, to treat mucosal bleeding during 
the study
Any medications deemed necessary by the subject’s physician to treat 
or prevent any medical condition
Any over-the-counter medication used by the subject to treat 
symptoms or signs
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

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10.5 Subject Diary
An e-diary will be provided to each subject at the screening visit to record the following 
information:

Infusion record for BAX 855

Infusion record for ADVATE

Details of bleeding episodes and response to treatment 

Untoward events

Concomitant medications (including immunizations) and non-drug 
therapies

PROs
Subjects and/or their legally authorized representatives will be trained on use of the diary 
during the screening visit. Diaries will be provided in electronic form and remain with the 
subject for the duration of the study. The investigator will review the diary for 
completeness and request missing information periodically and in a timely manner. 
Untoward events recorded in the diary will be reported as AEs according to the 
investigator’s discretion and clinical judgment.
Subject entries in the diary will serve as source records. During study participation, the 
investigator has access to the database holding the subject diary data. After study closure, 
the investigator will receive diary records for their subjects, including audit trail records, 
in PDF format. The data will be transmitted to the eCRF by a validated transfer. 
10.6 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).
Subjects have the option to exit the study once they have completed 100 EDs with 
BAX 855. Subjects can continue for an additional 50 EDs, or until the sponsor deems the 
BAX 855 study complete.
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)), study terminated by sponsor, or other 
(reason to be specified by the investigator, eg, technical problems). Regardless of the 

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reason, all data available for the subject up to the time of completion/discontinuation 
should be recorded in the appropriate eCRF. 
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
Schedule of Study Procedures and Assessments and Supplement 20.2, Clinical 
Laboratory Assessments.
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. 
10.7 Procedures for Monitoring Subject Compliance
Subject compliance with the prescribed BAX 855 prophylaxis regimen will be monitored 
by review of subject diaries as described in Section 10.5. Other study procedures will be 
performed under the direct supervision of the investigator/a licensed healthcare 
professional at the study site, and thus, no other procedures for monitoring will be 
employed. 
11. ASSESSMENT OF EFFICACY
11.1 Annualized Bleed Rate (ABR)
The primary measure of efficacy is the ABR. The ABR will be assessed based upon each 
individual bleeding episode, spontaneous or traumatic, recorded in the subject’s diary, 
and/or recorded in the physician/nurse/clinic notes. A bleeding episode is defined as 
subjective (eg, pain consistent with a joint bleed) or objective evidence of bleeding which 
may or may not require treatment with FVIII. Bleeding episodes occurring at the same 

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anatomical location (eg, right knee) with the same etiology (eg, spontaneous vs. injury) 
within 24 hours (± 2 hours) of onset of the first episode will be considered a single 
bleeding episode. Bleeding occurring at multiple locations related to the same injury (eg, 
knee and ankle bleeds following a fall) will be counted as a single bleeding episode.
11.2 Rate of Success of BAX 855 for Treatment of Bleeding Episodes
The key secondary measure of efficacy is the rate of success of BAX 855 to treat 
bleeding episodes. Success will be determined by the subject or subject’s caregiver. If the 
bleeding episode is managed in the clinic/hospital, the efficacy rating may be performed 
by the investigator. BAX 855 efficacy will be evaluated for each bleeding episode and 
will be assessed 24 hours (± 2 h) after initiating treatment using the efficacy rating scale 
(Table 3). Success is defined as a response of excellent or good at 24 hours post-infusion. 
11.3 Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
The number of BAX 855 infusions to treat each bleeding episode is determined by the 
subject, his caregiver, and/or investigator, and is based upon the subject’s response to 
treatment, using the efficacy rating scale in Table 3. An infusion is defined as completion 
of administration of the calculated dose of BAX 855. If an infusion is interrupted, eg, due 
to vascular access issues, and must be re-started, it will be recorded as 1 infusion. If an 
infusion is terminated for any reason prior to completion of infusion and not restarted, it 
will be recorded as an infusion; reasons for interruption of the infusion will be recorded.
11.4 Time Intervals Between Bleeding Episodes
The time interval between bleeding episodes will be calculated based upon the date and 
time reported for each bleeding episode. The subject, his caregiver, and/or investigator
will determine when a bleeding episode has occurred (see Section 11.1 above). The time 
interval will be defined as the date/time from when a recent bleed is stopped to the start 
day/time of the next bleeding episode.
11.5 Weight-Adjusted Consumption of BAX 855
Weight-adjusted consumption of BAX 855 will be determined based upon the amount of 
BAX 855 infused, as record in subject’s diary and the subject’s weight, as measured at 
the study site.

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12. ASSESSMENT OF SAFETY
12.1 Adverse Events
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. 
12.2 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). Seroconversion to HBV is only considered an 
SAE in the absence of vaccination; seroconversion of HBsAb from 
negative to positive will not be considered an SAE (or an AE)

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Development of a confirmed inhibitor to FVIII with an inhibitor level 
≥0.4 BU, as measured by the Nijmegen assay modification of the 
Bethesda assay
Severe hypersensitivity/allergic reactions to BAX 855
12.3 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.
12.4 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.5 Severity
Subjects transitioning from a prior BAX 855 study who experienced an AE that has not 
been resolved, will have any ongoing AEs and changes in severity of AEs, documented 
as part of the safety data for the BAX 855 continuation study.
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.

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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.
12.6 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 related to 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

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
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.
12.7 Preexisting Diseases
For subjects transitioning into this continuation study from a prior BAX 855 study, any 
AEs that occurred during these other BAX 855 studies and which are still ongoing in this 
continuation study will be considered as “ongoing” and not as a preexisting disease.
Preexisting diseases that are present before entry in to the study are described in the 
medical history, and 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, frequency, or duration of a preexisting disease, the event must be described on 
the AE CRF.
12.8 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.
For the purposes of this study, each unexpected AE experienced by a subject undergoing 
study-related procedures will be recorded on the AE CRF.

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12.9 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, for all 
subjects, 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 SAE Report and on the AE CRF. 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 non-serious untoward medical occurrence 
experienced by a subject undergoing study-related procedure(s) before the first IP 
exposure will be recorded on the AE CRF; these events will not be considered as AEs 
and will not be included in the analysis of AEs. 
12.10 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 (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 will be returned to the 
sponsor for inspection and analysis according to procedures.
12.11 Assessment of Adverse Events
For the purposes of this study, each of the following non-serious events experienced after 
the first IP exposure will not be considered an AE, and thus, not included in the analysis 
of AEs:

Hospital or clinic visits for administration of BAX 855

Hospitalization for routine bleeding episode management that could be managed 
in the clinic or home-setting 

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
Hospitalizations for planned medical or surgical procedures, eg, placement of a 
central venous line

Hospitalization or prolongation of hospitalization intended only for social reasons

Hospital admittance without in-patient hospitalization or emergency room 
visit/admittance (although the event triggering the visit may be an SAE)

Seroconversion after documented HAV/HBV vaccination prior to or during the 
study period

Bleeding episodes/hemophilia-related events
Bleeding episodes (epistaxis, gastrointestinal bleeding, musculoskeletal bleeding) are part 
of the underlying disease, and therefore, are not reported as AEs; they will be evaluated 
in the context of efficacy. 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). However, the investigator may decide that a bleeding 
episode is an AE if the episode also would have occurred in a healthy individual under 
the same circumstances.
For subjects entering from other BAX 855 studies, the outcome of any ongoing AEs will 
be reported in this continuation study.
For the purposes of this study and for all subjects, each non-serious untoward medical 
occurrence experienced by a subject undergoing study-related procedure(s) before the 
first IP exposure will be recorded on the AE CRF; these events are considered to be 
untoward medical occurrences and will not be considered as AEs and will not be included 
in the analysis of AEs. 
Each AE from the first IP exposure in this continuation study until study 
completion/discontinuation date will be recorded 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 12.4). Each AE 
will be evaluated by the investigator for:

Seriousness as defined in Section 12.5

Severity as defined in Section 12.8

Causal relationship to IP exposure as defined in Section 12.9

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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.
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.
AEs that were resolved in the previous BAX 855 studies will be documented as medical 
history for subjects who enter this continuation study. If a subject exited this continuation
study to participate in the surgery study, upon return, any AEs that started and resolved 
during the surgery study will be documented as (interim) medical history.
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 SAE Form within 24 hours after awareness; 
no additional reporting on CRFs is necessary.
12.12 Medical, Medication, and Non-Drug Therapy History
At screening, the subject’s medical history will be described for the following body 
systems including severity (mild, moderate, or severe as defined in Section 12.8). 
Medical history including surgery will include the following body systems, along with 
start and end dates, if known: eyes, ears, nose, and throat; respiratory; cardiovascular; 
gastrointestinal; musculoskeletal; neurological; endocrine; hematopoietic/lymphatic; 
dermatological; genitourinary; metabolic; infectious disease; and psychiatric.
All medications taken and non-drug therapies received from 30 days before enrollment 
until completion/termination will be recorded on the concomitant medications and non-
drug therapies CRFs.

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Any prior use of any PEGylated medication (name of drug, indication, and dates of use), 
at any time in the past, will be recorded on the CRF.
12.13 Physical Examinations
At screening and subsequent study visits (as described in Section 20), a physical 
examination will be performed on the following body systems being described as normal 
or abnormal: 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 12.10), 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.
12.14 Clinical Laboratory Parameters
All assessments will be performed at a central laboratory, according to the laboratory 
manual. 
12.14.1 Hematology, Clinical Chemistry, and Lipid Panel
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, as a 
percentage of total white blood cell count), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin concentration (MCHC), CD4 counts (at screening only) and 
platelet counts. 
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, alkaline 
phosphatase, blood urea nitrogen, creatinine, and glucose. 
The lipid panel will consist of cholesterol, very low density lipoprotein (VLDL), low 
density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides.
Blood will be obtained for assessment of hematology, clinical chemistry and lipid 
parameters at the screening visit, start of prophylaxis visit, follow-up visits, and end of 
study visit. Hematology, clinical chemistry and lipid assessments will be performed on 
EDTA-anticoagulated whole blood and serum, respectively, at the central laboratory. 

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12.14.2 Blood Type
For subjects who do not have documentation of their blood type in their medical record, 
blood ABO blood type will be determined. 
12.14.3 Factor VIII Activity and Antigen
FVIII activity will be measured using the one-stage clotting assay and the chromogenic 
assay. FVIII antigen will be measured using an ELISA assay. Blood will be obtained for 
the FVIII assessments at the screening visit, start of prophylaxis visit, follow-up visits, 
and end of study visit. 
12.14.4 Immunogenicity Assays
The primary study and safety assessment is the immunogenicity of BAX 855 which will 
be assessed by measurement of the following antibodies:

Inhibitory antibodies to FVIII – measured by the Nijmegen modification 
of the Bethesda assay

Binding antibodies to FVIII, BAX 855, and PEG. Both IgG and IgM 
antibodies will be measured using an ELISA assay.

Anti-CHO antibodies
To avoid an impact of residual FVIII in plasma, subjects must undergo at least a 72-hour 
washout period at the screening, follow-up and end of study visits. A 72-hour washout 
period is recommended prior to an unscheduled test.
A low titer (responder) inhibitor is defined as ≤ 5 BU but ≥ 0.4 BU. A high titer 
(responder) inhibitor is defined as > 5 BU by Nijmegen modification of the Bethesda 
assay. Inhibitors must be confirmed by 2 separate assessments within a 2 to 4 week 
period from the central laboratory.
Inhibitory antibodies to FVIII will be measured using the Nijmegen modification of the 
Bethesda inhibitor assay.
Binding antibodies (IgG and IgM) to FVIII and BAX 855, as well as to PEG, will be 
measured routinely using ELISA. Based on the variability of these tests, only samples 
with titers ≥ 1:80 can be confirmed and will be evaluated as positive. Furthermore, only 
increases of more than 2 titer steps between pre- and post-treatment samples will be 
considered positive for treatment-related antibody development. IgG subclass 1-4, IgA 
(using ELISA) and IgE antibodies (using ImmunoCaps, Phadia) may be assessed as 
clinically indicated. 

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The assay for antibodies to CHO protein will use CHO protein derived from cultures of 
untransfected cells. Testing for binding of anti-CHO protein antibodies will be performed 
on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG 
antibodies. Antibody-containing samples will be identified in a screening assay followed 
by a confirmatory assay to exclude false positive results.
Blood will be obtained for these assessments at the screening visit, start of prophylaxis 
visit, follow-up visits, and end of study visit.
12.14.5 Viral Serology
Viral serology testing will include HIV-1 and HIV-2 antibody, HBsAb, HBsAg, HBcAb, 
and HCV Ab. HCV or HIV titer will be confirmed by PCR for all subjects reported as 
HCV or HIV positive. All assessments will be performed at the screening visit only. Any 
positive test will be repeated using a new blood sample.
12.14.6 Assessment of Laboratory Values
12.14.6.1 Assessment of Abnormal Laboratory Values 
The investigator’s assessment of each abnormal standard clinical laboratory value (ie, 
hematology, clinical chemistry and lipids) is to 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 12.4 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 12.4), 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 was due to a preexisting 
disease (described in Section 12.7), due to a lab error, due to another issue that will be 
specified. Additional tests and other evaluations required to establish the significance or 
etiology of an abnormal result, 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. 
Any seroconversion result for human immunodeficiency virus (HIV), hepatitis B virus 
(HBV), hepatitis C virus (HCV) shall be re-tested.

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12.14.7 Biobanking
Backup samples should be taken and stored appropriately for additional analysis, if 
necessary. These samples may be used for re-testing, tests required per regulatory 
guidelines, further evaluation of an AE, or follow-up of other test results.
Back-up samples are planned at the screening, start of prophylaxis, follow-up, and end of 
study visits, 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).
Backup samples that remain after study testing is done may be stored and used for 
additional testing (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 the final study report has been 
completed and subsequently will be destroyed.
12.15 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 (for subjects 
less than 18 years of age at the time of enrollment)(in or cm) and weight (lb or kg) will 
also be collected. 
Vital signs will be measured at the screening visits, start of prophylaxis visit, follow-up 
visits, and end of study visit.
Blood pressure will be measured when subjects are in the sitting 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). If 
assessed as an AE, the medical diagnosis (preferably), symptom, or sign, will be recorded 
on the AE CRF. Additional tests and other evaluations required to establish the 
significance or etiology of an abnormal result, 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.
13. STATISTICS
13.1 Sample Size and Power Calculations
In total, approximately 250 subjects will be enrolled in this study. This sample size is 
based on the sample size calculations of the other BAX 855 studies (including the phase 

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2/3 pivotal, surgery, pediatric PTP), as well as the guideline 
EMA/CHMP/BPWP/144533/2009. 
13.2 Datasets and Analysis Cohorts
13.2.1 Safety Analysis Set
The safety analysis set will comprise all subjects treated with at least 1 BAX 855
infusion. All safety analyses will be performed on the safety analysis set. 
13.2.2 Full Analysis Set
The full analysis set will be the same as the safety analysis set. All efficacy analyses will 
be performed on the full analysis set.
13.2.3 Per Protocol Analysis Set
The per protocol (PP) analysis set will comprise all subjects from full analysis set who 
have no major deviations from the protocol affecting the study results. Major protocol 
deviations are defined in the Protocol Deviation Plan.
13.3 Handling of Missing, Unused, and Spurious Data
Missing data will not be imputed.
13.4 Methods of Analysis
13.4.1 Primary Outcome Measure
13.4.1.1 Primary Safety Outcome Measure
The number and proportion (Clopper-Pearson exact 95% CI) of subjects who develop 
inhibitory antibodies to FVIII will be provided. Only the inhibitory antibodies developed 
after the first exposure to BAX 855 will be included in the analysis, the inhibitory 
antibodies developed before the first exposure to BAX 855 will be listed separately. 
13.4.1.2 Primary Efficacy Outcome Measure
The primary outcome measure, the spontaneous ABR, will be assumed to have a negative 
binomial distribution, mean ABR (95% CI) will be estimated using a general estimating 
equation (GEE) model framework (with a logarithmic link function which is the default 
for the negative binomial distribution), treatment regimen as a fixed effect and subject 
effect as a random effect, age at baseline as a continuous covariate, and the logarithm of 
follow-up time (in years) as an offset.

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13.4.2 Secondary Outcome Measures
13.4.2.1 Total ABR 
The mean total ABR (spontaneous and traumatic bleeding episodes) (95% CI) will be 
estimated and described similarly as the primary efficacy outcome, using a general 
estimating equation (GEE) model with subject effect as a random effect, age at baseline 
as a continuous covariate, and the logarithm of follow-up time (in years) as an offset.
13.4.2.2 Rate of Success of BAX 855 for Treatment of Breakthrough Bleeding 
Episodes
Success will be defined as a rating of excellent or good using the efficacy rating scale 24 
hours after initiation of BAX 855 treatment for the bleeding episode.
Success proportion (95% CI) will be estimated within a general estimating equation 
(GEE) model framework pooled. The model will account for the fixed effects, bleeding 
episode severity, age at baseline as a continuous covariate, and the random subject effect. 
For the dependent variable (success: yes/no) a binomial distribution and a log link will be 
assumed, and for the subject effect (defined by a repeated statement) an independence 
correlation structure will be used to start the estimation. Estimated model parameter 
values and CI limits will then be back-transformed to the original scale by 
exponentiation.
13.4.2.3 Number of BAX 855 Infusions for the Treatment of Bleeding Episodes
Frequency tables will be prepared for the number of infusions required for the treatment 
of bleeding episodes. The median number of infusions (and nonparametric 95% CI) will 
be estimated. 
13.4.2.4 Time Intervals Between Bleeding Episodes
The average time interval between 2 consecutive bleeding episodes will be computed for 
each subject. If a subject does not have any bleeding episode then the observation will be 
censored at the end of the follow-up time of the respective subject. The median (95% CI) 
of those average time intervals between 2 bleeding episodes will be estimated.
13.4.2.5 Weight-Adjusted Consumption of BAX 855
Weight-adjusted consumption of BAX 855 for prophylaxis, treating bleeding episodes 
and in total per subject will be summarized separately as average number of BAX 855
infusions and average weight-adjusted consumption of BAX 855 per month. Only the 
bleeding episodes consumption with BAX 855 will be summarized.

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13.4.3 Patient Reported Outcomes
13.4.3.1 Haemo-SYM
Higher scores on the Haemo-SYM indicate worse symptom severity. Changes from 
baseline to end of treatment in the Haemo-SYM scores will be tested for 
statistical significance using a Wilcoxon test for paired samples. Improvement in the 
Haemo-SYM pain subscale of at least 11 points decreasing will be considered a 
meaningful improvement (a 1 point change on each pain question). Number and 
proportion of subjects with meaningful improvement in the Haemo-SYM pain subscale 
will be tabulated.
13.4.3.2 SF-36
Lower scores on SF-36 indicate worse HRQoL. Changes from baseline to end of 
treatment in the SF-36 scores will be tested for statistical significance, using a Wilcoxon 
test for paired samples. Improvement in the SF-36 scale of at least 3 points increasing 
will be considered a meaningful improvement. Number and proportion of subjects with 
meaningful improvement in the SF-36 will be tabulated.
13.4.4 Safety Analysis
Frequency counts and percentages will be calculated for SAEs, occurrence of inhibitory 
and binding antibodies, occurrence of severe allergic reactions, and occurrence of 
thrombotic events. 
AEs that occurred during or after treatment will be presented in summary tables. AEs will 
be cross-tabulated for relatedness, seriousness, and severity. AEs will be categorized 
according to the MedDRA dictionary and summarized by system organ class and 
preferred term. 
Vital signs and clinical laboratory parameters at the start of prophylaxis visit, the follow-
up visits, and the end of study visit will be descriptively summarized.
13.4.5 Exploratory Outcome Measures 
The exploratory outcome measures will be descriptively summarized and listed.
13.5 Planned Interim Safety Review of the Study
Two (2) interim safety reviews are planned for this study. The results of the safety 
reviews will not impact the study design and sample size.
An additional safety review is planned upon completion of the phase 2/3 pivotal study.

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13.5.1 Interim Safety Review 1
This interim safety review will be conducted when 35 subjects complete 6 months 
BAX 855 treatment at 30 to 80 IU/kg q5d. 
Descriptive statistics of ABR of this period will be provided, in addition, the number and 
percentage (95% CI) of subjects with ABR = 0 in this 6 months observed period will be 
provided.
13.5.2 Interim Safety Review 2
This interim safety review will be performed when 20 subjects complete 6 months of 
BAX 855 treatment at 30 to 80 IU/kg q7d.
The analysis of this interim will be the same as for the first interim safety review.
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.
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.

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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.
15.5 Non-Compliance with the Protocol
The investigator may deviate from the protocol 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 (Baxter) will also ensure the responsible ethics committee is 
notified of the urgent measures taken in such cases according to local regulations.

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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.
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 informed consent 
form 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 informed consent form will be reviewed by the sponsor and 
approved by the EC and regulatory authority(ies), where applicable, (see Section 16.2). 

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The informed consent form 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 informed consent form, 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.
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 informed 
consent will be updated, if necessary. This new information and/or revised informed 
consent form, that have 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 Data Monitoring Committee 
This study will not require a Data Monitoring Committee (DMC) for routine or ad hoc 
safety reviews. 
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” 
(Section 8.7), 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.

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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.
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. 

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20. SUPPLEMENTS
20.1 Schedule of Study Procedures and Assessments
Procedures/Assessments
Screening Visita
Study Visits
End of Study Visitb
(28 d ± 2 Wks 
After Last Dose)
Start of Prophylaxis
(Up to 7 d Prior to First 
Prophylaxis)
Follow-Up
(6 Wks [- 1 or + 2 Wks])
& Every 3 Mo [± 4 Wks])
Informed Consentc
X
Eligibility Criteria
X
Medical Historyd
X
Medication Historye
X
Concomitant Medicationsf
X
X
X
X
Non-drug Therapies
X
X
X
X
Physical Examg
X
X
X
X
Adverse Events 
Xh
X
X
X
Laboratoriesi
X
X
X
X
Vital Signsj
X
X
X
X
Bleeding episodes and their 
Treatmentk
X
X
X
X
PROsl
X
X
Patient e-diarym
X
X
X
X
IP Treatment
X
X
ABR Estimationn
X
a
The screening visit procedures, including laboratory evaluations, are to be completed within 45 days prior to the first infusion of BAX 855. 
Screening procedures for BAX naïve subjects include: confirmation of diagnosis & severity; family history of hemophilia; documentation of a 
mutation, if known; presence of any target joints; all FVIII replacement therapies used within the last year (see Section 10.3.1 for additional details).
b
Includes for cases of withdrawal or discontinuation.
Continued on Next Page

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Continued
c
Occurs at enrollment (prior to any study-specific procedure).
d
Medical history to include hemophilia history.
e
Medication history to include documentation of all FVIII replacement therapies used within the last year.
f
Concomitant medications in the last 30 days and any prior history of use of any PEGylated medication (eg, PEG-interferon) at any time in the past.
g
Physical exam to include a measurement of height (cm) (for subjects less than 18 years of age at enrollment) and weight (kg).
h
For subjects transitioning from a prior BAX 855 study into this continuation study.
i
For laboratory assessments, see Section 20.2.
j
Vital signs to include body temperature (ºC), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). 
k
Indicates that adverse events, medications, non-drug therapies, and bleeding episodes and their treatment will be continuously monitored and 
specifically measured at these times.
l
PROs to include the following depending on patient age: bleed and pain severity using Haemo-SYM (age 18 and older), health-related quality of life 
using SF-36 (≥14 years of age), patient satisfaction with treatment using the Satisfaction Questionnaire, and Patient Activity Level.
m
E-diaries are to include patient documentation of bleeds, treatment administered and response to BAX 855, and other data as detailed in Section 10.5.
n
At each consecutive 6 months visit.

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20.2 Clinical Laboratory Assessments
Assessments
Screening Visit
Study Visits
End of Study Visita
(28 d ± 2 Wks 
After Last Dose)
Start of Prophylaxis
(Up to 7 d Prior to First 
Prophylaxis)
Follow-Up
(6 Wks [- 1 or + 2 Wks]
& Every 3 Mo [± 4 Wks])
Hematology
Hemoglobin 
W
W
W
W
Hematocrit
W
W
W
W
Red blood cell count
W
W
W
W
White blood cell count with differentialb
W
W
W
W
Mean corpuscular volume (MCV)
W
W
W
W
Mean corpuscular hemoglobin 
concentration (MCHC)
W
W
W
W
Platelet count
W
W
W
W
CD4 count
W
Clinical Chemistry
Sodium
S
S
S
S
Potassium
S
S
S
S
Chloride
S
S
S
S
Bicarbonate
S
S
S
S
Total protein
S
S
S
S
Albumin
S
S
S
S
Alanine aminotransferase (ALT)
S
S
S
S
Aspartate aminotransferase (AST)
S
S
S
S
Total bilirubin
S
S
S
S
Alkaline phosphatase
S
S
S
S
Blood urea nitrogen (BUN)
S
S
S
S
Creatinine
S
S
S
S
Glucose
S
S
S
S
Lipid panelc
S
S
S
S
Viral serologyd
HIV-1Ab
S

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Assessments
Screening Visit
Study Visits
End of Study Visita
(28 d ± 2 Wks 
After Last Dose)
Start of Prophylaxis
(Up to 7 d Prior to First 
Prophylaxis)
Follow-Up
(6 Wks [- 1 or + 2 Wks]
& Every 3 Mo [± 4 Wks])
HIV-2 Ab
S
HBcAb
S
HBsAb
S
HBsAg
S
HCVAb 
S
Specialty Tests
Blood typee
W
FVIII Tests
1-stage clotting FVIII activity
P
P
P
P
FVIII chromogenic activity
P
P
P
P
FVIII antigen
P
P
P
P
Immunogenicity Assaysf
Inhibitory Abs to FVIII
P
P
P
P
Binding Abs to FVIII, BAX 855 and PEG
P
P
P
P
Anti-CHO Abs
P
P
P
P
Abbreviations: W = whole blood; P = plasma; S = serum.
a
Includes for cases of withdrawal or discontinuation.
b
White blood cell count to include basophils, eosinophils, lymphocytes, monocytes, and neutrophils.
c
Lipid panel to include cholesterol, VLDL, LDL, HDL, and triglycerides.
d
For viral serology, any positive viral antibody test will be repeated using a new blood sample. Any HCV positive sample will be tested by PCR for 
viral titer.
e
If historical data on blood group type is available, this may be recorded in the CRF and blood type does not need to be measured.
f
For binding antibodies, both IgG and IgM antibodies will be measured. A 72-hour washout period is required.

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20.3 Karnofsky Score
Karnofsky Score for Performance Status
Score
Definition
100
Normal, no complaints; no evidence of disease
90
Able to perform normal activity; minor signs or symptoms of disease
80
Able to perform normal activity with effort; some signs or symptoms of disease
70
Cares for self, unable to perform normal activity or to do active work
60
Requires occasional assistance but is able to care for most of own needs
50
Requires considerable assistance and frequent medical care
40
Disabled; requires special care and assistance
30
Severely disabled; hospitalization indicated, although death not imminent
20
Very sick; hospitalization necessary; active supportive treatment required
10
Moribund; Fatal processes progressing rapidly
0
Dead
Source: Karnofsky et al.9

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21. REFERENCES
1. 
National Hemophilia Foundation. MASAC Recommendation Concerning 
Prophylaxis (Regular Administration of Clotting Factor Concentrate to Prevent 
Bleeding). MASAC 179. 4-11-2007. National Hemophilia Foundation (NSF). 
2. 
National Hemophilia Foundation. MASAC Recommendation Concerning 
Prophylaxis (Regular Administration of Clotting Factor Concentrate to Prevent 
Bleeding). MASAC #170. 4-22-2006. National Hemophilia Foundation (NSF). 
3. 
Björkman S, Berntorp E. Pharmacokinetics of coagulation factors: clinical 
relevance for patients with haemophilia. Clin.Pharmacokinet. 2001;40:815-832.
4. 
Björkman S, Folkesson A, Jönsson S. Pharmacokinetics and dose requirements of 
factor VIII over the age range 3-74 years: A population analysis based on 50 
patients with long-term prophylactic treatment for haemophilia A. 
Eur.J.Clin.Pharmacol. 2009;65:989-998.
5. 
Valentino LA, Mamonov V, Hellmann A et al. A randomized comparison of two 
prophylaxis regimens and a paired comparison of on-demand and prophylaxis 
treatments in hemophilia A management. J.Thromb.Haemost. 2012;10:359-367.
6. 
Committee for Medicinal Products for Human Use. Guideline on the clinical 
investigation of recombinant and human plasma-derived factor VIII products. 
EMEA/CHMP/BPWP/144533/2009, 19. 2009. London, European Agency for the 
Evaluation of Medicinal Products (EMEA). 
7. 
White GC, Rosendaal F, Aledort LM et al. Definitions in hemophilia. 
Recommendation of the scientific subcommittee on factor VIII and factor IX of the 
scientific and standardization committee of the International Society on Thrombosis 
and Haemostasis. Factor VII and Factor IX Subcommittee. Thromb.Haemost. 
2001;85:560-575.
8. 
Boggio LN, Kessler CM. Hemophilia A and B. In: Kitchens C, Alving B, Kessler 
C, eds. Consultative Hemostasis and Thrombosis. Philadelphia: Saunders Elsevier; 
2007:45-59.
9. 
Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The use of nitrogen 
mustards in the palliative treatment of carcinoma. With particular reference to 
bronchogenic carcinoma. Cancer. 1948;1:634-656.

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22. SUMMARY OF CHANGES
Protocol 261302: Amendment 1 2013 OCT 02
Replaces: Original: 2013 JUN 18
In this section, changes from the previous version of the Original Protocol, dated 
2013 JUN 18, are described and their rationale is given.
1. Throughout the document
Description of Change: Minor grammatical and/or administrative changes have 
been made.
Purpose for the Change: To improve the readability and/or clarity of the protocol.
2. Study Synopsis, 7.2 Primary Objectives, and 8.4.1 Primary Outcome Measures
Description of Change: “neutralizing FVIII inhibitors” were reworded as 
“inhibitory antibodies to FVIII”.
Purpose for the Change: To align with other sections of the protocol, the pivotal 
and surgery studies.
3. Study Synopsis, Sections 9.1 Inclusion Criteria and 9.2 Exclusion Criteria 
Description of Change: Inclusion/Exclusion criteria are applied to all study 
subjects.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
4. Synopsis, Sections 10.3 Screening and Study Visits, 10.3.3 Follow-up Visits 20.1 
Schedule of Study Procedures and Assessments and 20.2 Clinical Laboratory 
Assessments
Description of Change: A timing of the first Follow-up visit changed from 1 
month (± 2 weeks) to 6 weeks (- 1 or + 2 weeks).
Purpose for the Change: To ensure immunogenicity testing after 10-15 exposure 
days for BAX 855 naïve subjects.
5. Section 6.1 Description of Investigational Product
Description of Change: Additional information was added to more completely 
describe the BAX 855 molecule, the purpose of this study, how the data with 
BAX 855 be assessed in this study and the dosing rationale in this study.
Purpose for the Change: To add more clarity and specific information to support
the rationale for this study and the study design including dosing rationale.

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6. Sections 8.2 Overall Study Design, 8.6.3 Description of Treatment, 9.1 Inclusion 
Criteria, 9.2 Exclusion Criteria, 10.3.1 Screening Visit and 10.3.2 Start of 
Prophylaxis Visit 
Description of Change: Additional wording was added to transition of subjects 
from other BAX 855 studies.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
7. Section 8.2 Overall Study Design, Section 10.3.1 Screening Visit, and 
Section 10.3.4 End of Study Visit
Description of Change: A minimal duration of the washout period was changed 
to 72 hours. 
Purpose for the Change: To align with the pivotal study and to avoid additional 
risk of bleeding episodes.
8. Section 8.2.1 Treatment for Surgery or Dental Procedures
Description of Change: The section was added to provide clarity how subjects 
will be transferred to and from the surgery study (261204), what factor will be 
used, what and where to clinical data will be recorded.
Purpose for the Change: Clarification and to align with the surgery study.
9. Section 8.4.1 Primary Outcome Measures, Section 10.3.1. Screening Visit, 
Section 10.3.2 Start of Prophylaxis Visit, Section 10.3.3 Follow-up Visits,
Section 10.3.4 End of Study, Section 12.14.4 Immunogenicity Assessments, and 
Section 20.3 Clinical Laboratory Assessments
Description of Change: A requirement for a 72-hour washout period before 
immunogenicity tests was added. 
Purpose for the Change: To implement the laboratory requirements and to avoid 
false results.
10. Section 8.6.3.2 Immune Induction for Inhibitor Development, Section 9.3 
Withdrawal and Discontinuation, and Section 12.2 Serious Adverse Events
Description of Change: The level of detectable FVIII inhibitory antibodies 
determined by the central laboratory was changed to 0.4 BU.
Purpose for the Change: The central laboratory was validated for this value.

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11. Section 10.3.1 Screening Visit
Description of Change: Additional wording was added to clarify the assessment 
for the subjects transitioning from other BAX 855 studies.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
12. Section 10.5 Subject Diary
Description of Change: Additional wording was added to clarify the section.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
13. Section 12.9 Untoward Medical Occurrences and 12.11 Assessment of Adverse 
Events
Description of Change: Description of non-serious events was moved from
Section 12.9 to Section 12.11.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
14. Section 12.11 Assessment of Adverse Events
Description of Change: Additional wording was added to clarify severity rating 
for adverse events will be recorded for subjects transitioned from other BAX 855
studies.
Purpose for the Change: Clarification and to align with the pivotal and surgery 
studies.
15. Section 12.14.7 Biobanking
Description of Change: Additional wording was added to clarify biobanking.
Purpose for the Change: Clarification.
16. Section 13.5 Planned Interim Analysis of the Study
Description of Change: A safety review was added.
Purpose for the Change: To ensure safety and to be able to provide safety review 
data upon completion of the pivotal study.

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INVESTIGATOR ACKNOWLEDGEMENT
Product: PEGylated rFVIII (BAX 855)
STUDY TITLE: A Phase 3b Continuation study of the Safety and Efficacy of 
PEGylated Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of 
Bleeding in Previously Treated Patients with Severe Hemophilia A
Phase 3b Continuation Study of the Safety and Efficacy of Prophylactic BAX 855 in 
PTPs with Severe Hemophilia A
PROTOCOL IDENTIFIER: 261302
CLINICAL TRIAL PHASE: Phase 3B
AMENDMENT 1: 2013 OCT 02
Replaces: Original 2013 JUN 18
OTHER PROTOCOL ID(s)
NCT Number: NCT01945593
EudraCT Number: 2013-002236-24
IND NUMBER: 15299
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