An Open-Label, Multicenter, Evaluation of the Long-Term Safety and Efficacy of Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) in the Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects With Hemophilia B
Phase: PHASE3
Conditions: Severe Hemophilia B
Sponsor: Bioverativ Therapeutics Inc.

 
CONFIDENTIAL 
The information contained herein may not be used, disclosed, or published without the written consent of 
Biogen Idec MA Inc. 
1 
 
 
 
 
 
 
 
Biogen Idec MA Inc.
14 Cambridge Center
  Cambridge, MA 02142, USA 
 
 
PROTOCOL NUMBER: 
9HB01EXT 
Biogen Idec Research Limited
Innovation House
70 Norden Road
Maidenhead Berkshire
SL6 4AY
United Kingdom
PHASE OF DEVELOPMENT: 
3 
 
 
PROTOCOL TITLE: An Open-Label, Multicenter Evaluation of the Long-Term Safety and 
Efficacy of Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) in the 
Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects With 
Hemophilia B 
 
EUDRA CT NO: 
 
2011-003075-11 
 
DATE: 
13 November 2013 
Version 4 
FINAL 
 
Supersedes previous Version 3 dated 20 June 2012 
 

Protocol 9HB01EXT 
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Long Term Use of rFIXFc
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TABLE OF CONTENTS 
1. 
SPONSOR INFORMATION AND CONTACT INFORMATION .............................9 
2. 
LIST OF ABBREVIATIONS.....................................................................................11 
3. 
SYNOPSIS .................................................................................................................13 
4. 
SCHEDULE OF EVENTS FOR STUDY 9HB01EXT..............................................21 
4.1. 
Screening and Treatment Period .................................................................................21 
4.2. 
Surgery Visits .............................................................................................................26 
5. 
INTRODUCTION ......................................................................................................28 
5.1. 
Profile of Previous Experience ...................................................................................28 
5.1.1. 
Therapies for Hemophilia B .......................................................................................28 
5.1.2. 
rFIXFc .........................................................................................................................29 
5.1.3. 
Summary of Clinical Experience with rFIXFc ...........................................................29 
5.2. 
Study Rationale ...........................................................................................................30 
5.3. 
Rationale for Dose and Schedule Selection ................................................................30 
5.3.1. 
On-demand (Episodic) Treatment ..............................................................................31 
5.3.2. 
Prophylaxis Regimens ................................................................................................31 
5.3.3. 
Surgery and Rehabilitation .........................................................................................32 
5.4. 
Potential Risks and Benefits .......................................................................................33 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................34 
6.1. 
Objectives ...................................................................................................................34 
6.1.1. 
Primary Objective .......................................................................................................34 
6.1.2. 
Secondary Objective ...................................................................................................34 
6.2. 
Endpoints ....................................................................................................................34 
6.2.1. 
Primary Endpoint ........................................................................................................34 
6.2.2. 
Secondary Endpoints ..................................................................................................34 
6.2.3. 
Major Surgery Endpoints ............................................................................................34 
6.2.4. 
Patient-Reported and Health Outcomes Endpoints ....................................................35 
7. 
STUDY DESIGN .......................................................................................................37 
7.1. 
Study Overview ..........................................................................................................37 
7.1.1. 
Dose-Limiting Toxicity ..............................................................................................38 
7.1.2. 
Inhibitor Testing .........................................................................................................38 

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7.1.3. 
Anti-rFIXFc Antibody Testing ...................................................................................39 
7.1.4. 
Bleeding Episodes ......................................................................................................39 
7.1.4.1. 
Information to be Recorded ........................................................................................39 
7.1.4.2. 
Procedure to Treat the Bleeding Episode ...................................................................40 
7.1.4.3. 
Dose and/or Interval Modification Following Bleeding Episodes .............................41 
7.2. 
Overall Study Duration and Follow-Up .....................................................................41 
7.2.1. 
Screening ....................................................................................................................42 
7.2.2. 
Treatment ....................................................................................................................42 
7.2.3. 
Follow-Up ...................................................................................................................42 
7.3. 
Study Stopping Rules .................................................................................................42 
7.4. 
End of Study ...............................................................................................................42 
8. 
SELECTION OF SUBJECTS ....................................................................................43 
8.1. 
Inclusion Criteria ........................................................................................................43 
8.2. 
Exclusion Criteria .......................................................................................................43 
9. 
ENROLLMENT AND REGISTRATION PROCEDURES ......................................44 
9.1. 
Enrollment and Screening ...........................................................................................44 
9.2. 
Registration of Subjects ..............................................................................................44 
9.3. 
Blinding Procedures ....................................................................................................44 
10. 
TREATMENT OF SUBJECTS ..................................................................................45 
10.1. 
Study Treatment Schedule and Administration ..........................................................45 
10.1.1. 
Prophylaxis Regimens ................................................................................................45 
10.1.2. 
On-demand (Episodic) Treatment ..............................................................................46 
10.1.3. 
Surgery ........................................................................................................................46 
10.2. 
Treatment Precautions ................................................................................................47 
10.3. 
Modification of Dose and/or Treatment Schedule ......................................................47 
10.3.1. 
Prophylaxis Regimen ..................................................................................................47 
10.3.2. 
On-demand (Episodic) Treatment ..............................................................................47 
10.4. 
Treatment Compliance ................................................................................................48 
10.5. 
Concomitant Therapy and Procedures ........................................................................48 
10.5.1. 
Concomitant Therapy .................................................................................................48 
10.5.1.1. 
Allowed Concomitant Therapy ...................................................................................48 
10.5.1.2. 
Disallowed Concomitant Therapy ..............................................................................48 

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10.5.2. 
Concomitant Procedures .............................................................................................48 
10.6. 
Continuation of Treatment ..........................................................................................49 
11. 
WITHDRAWAL OF SUBJECTS FROM STUDY TREATMENT AND/OR 
THE STUDY ..............................................................................................................50 
11.1. 
Discontinuation of Study Treatment ...........................................................................50 
11.2. 
Withdrawal of Subjects From Study ...........................................................................51 
12. 
STUDY TREATMENT MANAGEMENT ................................................................52 
12.1. 
rFIXFc (BIIB029) .......................................................................................................52 
12.1.1. 
rFIXFc Preparation .....................................................................................................52 
12.1.2. 
rFIXFc Storage ...........................................................................................................53 
12.1.3. 
rFIXFc Handling and Disposal ...................................................................................53 
12.1.4. 
rFIXFc Accountability ................................................................................................53 
13. 
EFFICACY ASSESSMENTS ....................................................................................54 
13.1. 
Clinical Efficacy Assessments ....................................................................................54 
13.2. 
Laboratory Efficacy Assessments ...............................................................................55 
13.3. 
Pharmacokinetic Assessments ....................................................................................55 
13.4. 
Pharmacodynamic Assessments .................................................................................55 
13.5. 
Additional Assessments ..............................................................................................55 
13.5.1. 
Hemophilia Joint Health Score ...................................................................................55 
13.5.2. 
Patient-Reported and Health Outcomes ......................................................................55 
13.5.3. 
Optional Laboratory Assessment ................................................................................56 
13.5.4. 
Archive Plasma Samples ............................................................................................57 
14. 
SAFETY ASSESSMENTS ........................................................................................58 
14.1. 
Clinical Safety Assessments .......................................................................................58 
14.2. 
Laboratory Safety Assessments ..................................................................................58 
15. 
SAFETY DEFINITIONS, MONITORING, AND REPORTING .............................59 
15.1. 
Definitions ..................................................................................................................59 
15.1.1. 
Serious Pretreatment Event .........................................................................................59 
15.1.2. 
Adverse Event .............................................................................................................59 
15.1.3. 
Serious Adverse Event ................................................................................................59 
15.2. 
Monitoring and Recording Events ..............................................................................60 
15.2.1. 
Serious Pretreatment Events .......................................................................................60 

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15.2.2. 
Adverse Events ...........................................................................................................60 
15.2.3. 
Serious Adverse Events ..............................................................................................60 
15.2.4. 
All Events ...................................................................................................................61 
15.2.5. 
Immediate Reporting of Serious Adverse Events .......................................................61 
15.2.5.1. 
Deaths .........................................................................................................................62 
15.3. 
Safety Classifications ..................................................................................................62 
15.3.1. 
Relationship of Events to Study Treatment ................................................................62 
15.3.2. 
Severity of Events .......................................................................................................63 
15.3.3. 
Expectedness of Events ..............................................................................................63 
15.4. 
Procedures for Handling Special Situations ...............................................................64 
15.4.1. 
Overdose .....................................................................................................................64 
15.4.2. 
Medical Emergency ....................................................................................................64 
15.4.3. 
Pregnancy ...................................................................................................................64 
15.4.4. 
Regulatory Reporting ..................................................................................................64 
15.5. 
Investigator Responsibilities .......................................................................................64 
15.6. 
Biogen Idec Responsibilities ......................................................................................65 
16. 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ...........66 
16.1. 
Description of Objectives ...........................................................................................66 
16.1.1. 
Primary Objective .......................................................................................................66 
16.1.2. 
Secondary Objective ...................................................................................................66 
16.2. 
Description of Endpoints ............................................................................................66 
16.2.1. 
Primary Endpoint ........................................................................................................66 
16.2.2. 
Secondary Endpoint ....................................................................................................66 
16.3. 
Demography and Baseline Disease Characteristics ....................................................66 
16.4. 
Efficacy .......................................................................................................................67 
16.4.1. 
Analysis Population ....................................................................................................67 
16.4.2. 
General Methods of Analysis .....................................................................................67 
16.4.3. 
Endpoint Analysis .......................................................................................................67 
16.4.3.1. 
Annualized Bleeding Episodes and Annualized rFIXFc Consumption .....................67 
16.4.3.2. 
Other Efficacy Endpoints ...........................................................................................67 
16.4.3.3. 
Surgery Endpoints ......................................................................................................68 
16.4.4. 
Additional/Exploratory Analysis ................................................................................68 

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16.5. 
Patient-Reported and Health Outcomes ......................................................................68 
16.5.1. 
Analysis Population ....................................................................................................68 
16.5.2. 
Methods of Analysis ...................................................................................................68 
16.5.2.1. 
Patient-Reported Outcomes ........................................................................................68 
16.5.2.2. 
Health Outcomes ........................................................................................................68 
16.6. 
Safety ..........................................................................................................................68 
16.6.1. 
Analysis Population ....................................................................................................68 
16.6.2. 
Methods of Analysis ...................................................................................................68 
16.7. 
Inhibitor Formation Data ............................................................................................69 
16.7.1. 
Analysis Population ....................................................................................................69 
16.7.2. 
Methods of Analysis ...................................................................................................69 
16.8. 
Optional Laboratory Assessments ..............................................................................69 
16.9. 
Interim Analyses .........................................................................................................69 
16.10. 
Sample Size Considerations .......................................................................................69 
17. 
ETHICAL REQUIREMENTS ...................................................................................70 
17.1. 
Declaration of Helsinki ...............................................................................................70 
17.2. 
Ethics Committee ........................................................................................................70 
17.3. 
Subject Information and Consent ...............................................................................70 
17.4. 
Subject Data Protection ..............................................................................................71 
17.5. 
Compensation for Injury .............................................................................................71 
17.6. 
Conflict of Interest ......................................................................................................71 
17.7. 
Registration of Study and Disclosure of Study Results ..............................................71 
18. 
ADMINISTRATIVE PROCEDURES .......................................................................72 
18.1. 
Study Site Initiation ....................................................................................................72 
18.2. 
Study Supplies ............................................................................................................72 
18.3. 
Quality Assurance .......................................................................................................72 
18.4. 
Monitoring of the Study..............................................................................................72 
18.5. 
Study Funding .............................................................................................................72 
18.6. 
Publications .................................................................................................................73 
19. 
FURTHER REQUIREMENTS AND GENERAL INFORMATION ........................74 
19.1. 
External Contract Organizations .................................................................................74 
19.1.1. 
Contract Research Organization .................................................................................74 

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19.1.2. 
Interactive Voice/Web Response System ...................................................................74 
19.1.3. 
Electronic Data Capture ..............................................................................................74 
19.1.4. 
Central Laboratories for Laboratory Assessments .....................................................74 
19.2. 
Changes to Final Study Protocol ................................................................................74 
19.3. 
Ethics Committee Notification of Study Completion or Termination ........................75 
19.4. 
Retention of Study Data ..............................................................................................75 
19.5. 
Study Report Signatory...............................................................................................75 
20. 
REFERENCES ...........................................................................................................76 
21. 
SIGNED AGREEMENT OF THE STUDY PROTOCOL .........................................78 
APPENDIX A. rFIXFc DOSING GUIDELINE FOR TREATMENT OF BLEEDING 
EPISODES ..................................................................................................................79 
APPENDIX B. HEMOPHILIA JOINT HEALTH SCORE (HJHS) ..........................................80 
APPENDIX C. 
 OF RESPONSE TO TREATMENT OF 
BLEEDING ................................................................................................................83 
APPENDIX D. 
 ASSESSMENT OF RESPONSE ...........................84 
APPENDIX E. PHYSICIAN ASSESSMENT OF RESPONSE TO TREATMENT 
DURING SURGERY .................................................................................................85 
APPENDIX F. PATIENT REPORTED OUTCOMES...............................................................86 
 
LIST OF TABLES 
Table 1: 
Screening and Treatment Period .................................................................................21 
Table 2: 
Surgery Visits .............................................................................................................26 
Table 3: 
Dosing Guidelines for rFIXFc Therapy in Hemophilia B ..........................................79 
 
 

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1. 
SPONSOR INFORMATION AND CONTACT INFORMATION 
This study is sponsored by Biogen Idec MA Inc. 
Biogen Idec MA Inc. 
14 Cambridge Center 
Cambridge, MA 02142 
USA 
Phone:  +1 617-679-2000 
Fax:  +1 617-679-2617 
Biogen Idec Research 
Ltd. 
Innovation House 
70 Norden Road 
Maidenhead, Berkshire  
SL6 4AY 
United Kingdom 
Phone:  +44-1628 501000 
Fax:  +44-1628 501010 
 
 
Biogen Idec Japan Ltd. 
Atago Green Hills Mori 
Tower 26F 
5-1Atago 2-chome 
Minato-ku  
Tokyo 105-6226 
Japan 
Phone:  +81 3 6402-7800 
Fax:  +81 3 6402-7850 
 
Biogen Idec Canada 
90 Burnahamthorpe Road West 
Suite 1100 
Mississauga, Ontario L5B 3C3 
Canada 
Phone:  +1 905-804-1444 
Fax:  +1 905-897-3222 
 
 
 
Biogen Idec Australia Pty Ltd 
Suite 1, Level 5, 123 Epping Rd 
North Ryde, NSW 2113 
Australia 
Phone: +61 2 8875 3900 
Fax: +61 2 9889 1162 
 
 
Primary contact for urgent medical issues: 
, Medical Research: 
 
, MD, PhD 
Biogen Idec MA Inc. 
 
 
 
 
 
 
 
 
 
Secondary contact for urgent medical issues: 
, Medical Research 
, MD 
Biogen Idec MA Inc. 
 
 
 
 
 
 
 
 

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Other Contacts: 
Clinical Research Organization: 
 
Quintiles 
 
 
4820 Emperor Boulevard 
 
 
Durham, NC 27703 USA 
Pharmacovigilance/SAE Reporting  
Quintiles Lifecycle Safety 
Local telephone and fax numbers for reporting to Quintiles Pharmacovigilance from each 
Study File. 
Please refer to the Study Reference Manual, Official Study Contact List for complete contact 
information. 

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2. 
LIST OF ABBREVIATIONS  
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUCinf 
Area under the activity versus time curve from the time of treatment 
administration (zero) extrapolated to infinity 
BU 
Bethesda Units 
BUN 
Blood urea nitrogen 
CHO-KLAT 
Canadian Hemophilia Outcomes-
 
Cl 
Clearance 
Cmax 
Maximum activity 
CRO 
Contract research organization 
DHA 
Directions for Handling and Administration 
dL 
Deciliter 
eCRF 
Electronic case report form 
ED 
Exposure day(s) 
EDC 
Electronic data capture 
eDiary 
Electronic patient diary (EPD) 
EOT 
End of Treatment 
FIX 
Factor IX 
FIX:C 
Factor IX coagulant activity 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HJHS 
Hemophilia Joint Health Score 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IU 
International Units 
IV 
Intravenous 
IXRS 
Interactive Voice and Web Response System 
Kg 
Kilogram 
MRT 
Mean residence time 
PHI 
Protected health information 
PK 
Pharmacokinetics 
PTP 
Previously treated patient 
QoL 
Quality of life 
rFIXFc 
Recombinant human coagulation Factor IX fusion protein 
SAE 
Serious adverse event 
SUSAR 
Suspected unexpected serious adverse event 
t1/2 
Half-life 
US 
United States 
Vss 
Volume of distribution at steady-state 
WBC 
White blood count 

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WFH 
World Federation of Hemophilia 
WHO 
World Health Organization 

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3. 
SYNOPSIS 
This is a brief summary.  For details refer to the body of the protocol. 
 
Protocol Number: 
9HB01EXT 
Protocol Title: 
An Open-Label, Multicenter Evaluation of the Long-Term Safety 
and Efficacy of Recombinant Human Coagulation Factor IX 
Fusion Protein (rFIXFc) in the Prevention and Treatment of 
Bleeding Episodes in Previously Treated Subjects With 
Hemophilia B. 
Version Number: 
4 
Name of Study Treatment: 
rFIXFc (BIIB029) 
Study Indication: 
Hemophilia B 
Phase of Development: 
3 
Rationale for the Study: 
To evaluate the long-term safety and efficacy of rFIXFc for the 
prevention and treatment of bleeding episodes in previously 
treated subjects with hemophilia B, and to allow subjects from the 
Phase 3 pivotal study (998HB102), the pediatric study 
(9HB02PED), or any other rFIXFc study (parent studies) to 
continue treatment with rFIXFc.   
Study Objectives and Endpoints: 
Objectives 
Primary:    
The primary objective of the study is to evaluate the long-term 
safety of rFIXFc in subjects with hemophilia B. 
Secondary:  
The secondary objective of this study is to evaluate the efficacy of 
rFIXFc in the prevention and treatment of bleeding episodes in 
subjects with hemophilia B. 
Endpoints 
Primary:   
The occurrence of inhibitor development. 
Secondary: 
 
The annualized number of bleeding episodes per 
subject 
 
The annualized number of spontaneous joint bleeding 
episodes per subject 
 
The total number of days of exposure per subject per 

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year
 
The consumption of rFIXFc as total dose per kg per 
subject per year  
 
response to his treatment regimen using a 4-point 
scale 
 
the 
treatment of bleeding episodes using a 4-point scale 
Endpoints for Major Surgeries: 
 
Investigator/Surgeon assessment of hemostatic 
response to surgery using the 4-point bleeding 
response scale 
 
Number of injections and dose per injection to 
maintain hemostasis during the surgical period 
 
Estimated blood loss (mL) during surgery and the 
post-operative period 
 
Number of blood product units transfused during 
surgery 
Patient-Reported and Health Outcome Endpoints:  
Subjects will be assessed only for those health outcomes and 
Quality of Life (QoL) parameters that they had been previously 
evaluated for in the parent study, and only for as long as they 
remain within the age range for the respective instrument.  This 
could include the following: 
 
Haem-A-QoL  
 
Haemo-QoL  
 
Hemo-Sat-Patient Satisfaction Scale Version 15 (for 
parents/guardians of subjects less than 18 years of 
age 
 
Canadian Hemophilia Outcomes-
Assessment Tool (CHO-KLAT) 
o Children, Version 2.0 (for children 
previously enrolled in study 9HB02PED who 
are less than 18 years of age). 
o Proxy, Version 2.0p (for parents/guardians 
of children who were previously enrolled in 
study 9HB02PED and are less than 18 years 
of age) 
 
EQ-5D-Y  

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EQ-5D-3L  
Other patient-reported and health outcomes related to hemophilia, 
as described in Section 6.2.4.  
 
Number of hospitalizations, excluding planned 
hospitalizations, elective surgery documented at 
Visit 1, and emergent surgery 
 
Number of emergency room visits 
 
Number of physician visits, excluding study visits 
 
Number of hospitalization days 
 
Number of days off work, school/daycare, or 
preschool 
 
Number of days off work for the parent/guardian or 
caregiver 
Study Design: 
This is an open-label, multicenter, long-term study of intravenous 
(IV) administration of rFIXFc in previously treated patients with 
hemophilia B, who completed the Phase 3 pivotal study 
(998HB102), pediatric study (9HB02PED), or any other trial with 
rFIXFc.  Treatment will be administered as a prophylactic 
(weekly, individualized, or personalized) regimen or on-demand 
(episodic) treatment. 
Rationale for Dose and Schedule 
Selection: 
The choice of treatment schedule will be based on the clinical 
profile of the subject and by the trough or peak (recovery) FIX 
activity values observed in the parent study, if needed.  Subjects 
12 years of age or older are permitted to change their regimen 
from prophylaxis to on-demand and from on-demand to 
prophylaxis during the study.  Subjects less than 12 years of age 
will receive a prophylactic regimen and will not have the option 
to change to on-demand treatment until they reach the age of 12 
years.  All treatment regimen changes will be discussed with the 
subject (or parent/guardian, as applicable).  All treatment regimen 
changes require the approval of the Sponsor Medical Monitor. 
The starting dose in study 9HB01EXT may be based on a 
parent rFIXFc study.  
In the completed Phase 3 pivotal study (998HB102), doses 
between 20 IU/kg and 100 IU/kg were generally well tolerated.  
In the pediatric study (9HB02PED), a starting dose of 
approximately 50 IU/kg to 60 IU/kg is being administered, with 
dose adjustments based upon trough and recovery levels obtained 
at scheduled visits.  The dose for routine prophylaxis and 
treatment of bleeding episodes may be adjusted up to 100 IU/kg 
and the interval decreased to twice a week.  In addition, higher 
doses of up to 150 IU/kg may be used to maintain adequate FIX 
activity and to prevent bleeding (e.g., during surgery). 

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Treatment Regimens:
For the purpose of analysis, the treatment regimen in 9HB01EXT 
means the actual treatment regimen(s) that subjects follow over 
the course of the study (i.e., not the regimen they started on in the 
parent study).  
On-demand (Episodic) Treatment 
The individual dose of rFIXFc to treat bleeding episodes will be 
bleeding event, and in some cases, FIX peak (recovery) levels.  
Pharmacokinetic (PK) data and dosing levels from the parent 
studies can also be used to guide dosing decisions.  Subjects less 
than 12 years of age will receive a prophylactic regimen and will 
not have the option to receive on-demand treatment until they 
reach the age of 12 years during the study. 
Prophylaxis Regimens 
The Investigator may consider the following options for 
prophylaxis to target a FIX trough of up to 5% above baseline, 
but is encouraged to use the lowest effective dose targeting a FIX 
trough level between 1% and 3%.  If bleeding episodes occur at 
FIX trough levels of 1% to 3%, further adjustments to dose or 
interval over the course of the study will target trough levels of up 
to 5%.     
 
Option 1:  Weekly Prophylaxis 
Dosing is approximately 20 IU/kg to 100 IU/kg every 7 days.  
observed in the parent rFIXFc study and his individual PK 
profile, trough, and/or peak (recovery) values. 
 
Option 2:  Individualized Prophylaxis 
Dosing is approximately 100 IU/kg every 8 to 16 days, or 2 times 
per month.  
clinical profile observed in the parent rFIXFc study, and his 
individual PK, trough, and/or peak (recovery) values. 
 
Option 3:  Personalized Prophylaxis 
If optimal prophylaxis dosing cannot be achieved using either of 
the above options, the Investigator may further personalize dosing 
to meet the needs of individual subjects. 
The Investigator may consider the following personalized dosing 
options: 
 
activity. 
 
Targeting a FIX trough level of >5%, if warranted by 
the bleeding history and/or activity level. 

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Dosing 2 times per week, e.g., approximately 
25 IU/kg twice weekly vs. approximately 50 IU/kg 
once weekly, for subjects who may have better 
control with such a regimen.  For pediatric subjects 
<12 years of age, the dose may be adjusted up to 
100 IU/kg twice weekly. 
The Investigator is not limited to the options above, and should 
consult the Medical Monitor for further consideration of a 
.  The personalized prophylaxis dosing 
option will require consultation with the Medical Monitor. 
Details for each dosing option, including, if applicable, date of 
change, new dose and/or dosing interval, and reason(s) for the 
regimen change will be recorded on the appropriate electronic 
case report form (eCRF) each time a change is made by the 
Investigator. 
Surgery/Rehabilitation 
If a subject requires surgery during this study, either emergent or 
elective, he may be treated with the dose and regimen of rFIXFc 
deemed appropriate for the type of surgery. 
All major surgeries must take place in a center that can provide 
study treatment, trained study personnel, post-operative 
assessments and hematological consultation by the Investigator or 
Sub-investigator.  If surgery does not take place in such a setting, 
the subject will be withdrawn from the study.  Specific provisions 
apply when a subject requires major surgery. 
Surgeries, elective or emergent, will be classified as major and 
minor as follows:   
 
Major surgery is defined as any surgical procedure 
(elective or emergent) that usually, but not always, 
involves general anesthesia and/or respiratory 
assistance, in which a major body cavity is penetrated 
and exposed, or a substantial impairment of physical 
or physiological functions is produced (e.g., 
laparotomy, thoracotomy, craniotomy, joint 
replacement, or limb amputation). 
 
Minor surgery is defined as any surgical procedure 
(elective or emergent) that does not involve general 
anesthesia and/or respiratory assistance (e.g., minor 
dental extractions, incision, and drainage of abscess, 
joint or other injections, or simple excisions).   
All major surgeries will be reported as serious adverse events 
(SAEs). 
Rehabilitation period 

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If surgery-related dosing is to be continued during post-operative 
rehabilitation, the dose of rFIXFc will be adjusted to achieve a 
trough at a sufficient level to maintain hemostasis, including 
during physical therapy.  These doses will be captured in the 
. 
Subjects will return to a regular rFIXFc regimen once all dosing 
for the post-operative period has been completed.  For subjects 
undergoing major surgery, a visit is required 1-2 weeks after 
surgery (Visit 3).  Visit 4 (Last Post-Operative Visit) occurs when 
the subject returns to a regular rFIXFc regimen as determined by 
the Investigator, and is required only if the subject did not return 
to a regular rFIXFc regimen at Visit 3.  For minor surgery, Visits 
3 and 4 are not performed. 
Study Location: 
Global 
Number of Planned Subjects: 
Approximately 120 subjects are planned to be treated in the study. 
Study Population: 
This study will be conducted in previously treated adult and 
pediatric subjects with hemophilia B who have participated in a 
previous rFIXFc clinical study. 
Detailed criteria are described in the body of the protocol. 
Duration of Treatment and 
Follow-up: 
Subjects are expected to be followed through at least 100 exposure 
days (EDs) to rFIXFc and may further continue in this study for up 
to 4 years or until rFIXFc is commercially available in the applicable 
participating country.    
Definition of Dose-Limiting 
Toxicity: 
No dose-limiting toxicity for rFIXFc has been identified. 
Statistical Methods: 
 
In general, subjects who enroll from the parent studies will have 
their study data integrated with their data for 9HB01EXT.  A parent 
study is defined as a study where subjects may be enrolled into 
9HB01EXT after study completion or at a time specified in the 
protocol. 
Demography and Baseline Disease Characteristics 
The analysis of demography and baseline disease characteristics will 
be based on the Safety Analysis Set.  The Safety Analysis Set 
includes all subjects who have received at least one dose of rFIXFc.  
Demographics and baseline disease characteristics will be 
summarized categorically and/or with descriptive statistics, as 
appropriate, using the data at the entry of the parent studies.   
Efficacy 
Subjects who receive at least one dose of rFIXFc will be included in 
the Full Analysis Set (FAS).  Efficacy analyses will be based on the 
FAS. 
Bleeding episodes will be annualized for each subject, and then 
summarized and tabulated by treatment arm, treatment regimen, or 

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age cohort, as appropriate, for the parent study and the 9HB01EXT 
treatment regimen(s).  These analyses will be performed for each 
type of bleed.  The number of spontaneous joint bleeding episodes 
and the consumption of rFIXFc will be annualized in a similar 
fashion and tabulated. 
Analysis of surgery endpoints will be performed for subjects who 
had surgery during the study, either emergently or electively.  
Summary statistics of surgery endpoints will be provided for the 
surgical/rehabilitation period. 
The periods in which data will be used for efficacy and surgical 
rehabilitation analyses will be defined in the statistical analysis plan.  
Data on bleeding and rFIXFc consumption will be based on the 
efficacy period; surgical evaluations will be based on the 
surgical/rehabilitation period.   
Patient-Reported and Health Outcomes 
Endpoints for patient-reported outcomes (Haem-A-QoL, Haemo-
QoL, Hemo-Sat-Patient, CHO-KLAT Children, CHO-KLAT Proxy, 
EQ-5D-Y and EQ-5D-3L) will be analyzed in a separate report.  
These endpoints will be analyzed by summarizing actual values and 
changes from baseline, as appropriate.   
Summary statistics of health outcome endpoints will be tabulated at 
each collection timepoint. 
Safety 
The Safety Analysis Set will include all subjects with at least one 
dose of rFIXFc.  For the analysis of safety, data in 9HB01EXT will 
be integrated with data from the parent studies, unless specified 
otherwise.  The incidence of adverse events (AEs) will be tabulated 
overall, by severity, and by relationship to treatment.  In addition, 
the incidence of AEs will be presented by ED intervals.  Findings in 
clinical lab values will be summarized by descriptive statistics. 
The proportion of subjects with inhibitors during rFIXFc 
administration will be provided with the exact (Clopper-Pearson) 
2-sided, 95% confidence interval. 
Interim Analysis: 
Interim analyses will be conducted during the study, as needed.  
Analyses will be descriptive in nature.  No formal comparisons are 
planned and no hypotheses will be formally tested.  The study has an 
open label design and thus, personnel conducting interim analyses 
will not be blinded to treatment assignments.   
Sample Size Determination: 
This is an extension study.  The samples size is based on sample 
sizes of studies 998HB102, and 9HB02PED and is estimated to be 
approximately 120 subjects, but may be increased based upon 
subject participation in other rFIXFc studies. 
Study Stopping Rules: 
The Sponsor may terminate this study at any time, after informing 
Investigators. 

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Study stopping is required if any of the following occur:
 
Three subjects develop a high-titer inhibitor (i.e. 
.00 BU/mL), identified and confirmed on 2 separate 
samples drawn approximately 2 to 4 weeks apart, and 
performed by the central laboratory using the Nijmegen-
modified Bethesda assay.  This number can be adjusted 
based on sample size when more subjects might be 
included into this trial from other rFIXFc studies. 
 
An unexpected, serious, or unacceptable risk to study 
subjects. 
If the study is stopped, the events will be investigated, enrollment 
will be stopped, and current subjects will stop dosing with rFIXFc.  
Surveillance Team, it is 
determined that the study should be permanently discontinued, then 
subjects will attend a final visit. 

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4. 
SCHEDULE OF EVENTS FOR STUDY 9HB01EXT 
4.1. 
Screening and Treatment Period 
Table 1: 
Screening and Treatment Period 
Tests and Assessments1 
Visit 12 
 
Visit 2 
Month 6 
(±2 weeks) 
Visit 3 
Month 12 
(±2 weeks) 
Visit 4 
Month 18 
(±2 weeks) 
Visit 5 
Month 24 
(±2 weeks) 
Visit 6 
Month 30 
(±2 weeks) 
Visit 7 
Month 36 
(±2 weeks) 
Visits Semi-
Annually (Every 
6 months) 
(±2 weeks) 
Informed Consent and Assent Forms 
X 
 
 
 
 
 
 
 
Eligibility Verification 
X 
 
 
 
 
 
 
 
Medical and Surgical History and 
Demographics3 
X 
 
 
 
 
 
 
 
Physical Examination 4 
X 
 
X 
 
X 
 
X 
X 
Vital Signs5 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
X 
 
X 
 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
rFIXFc 
dosing/dispensation/accountability6 
X 
X 
X 
X 
X 
X 
X 
X 
Nijmegen-modified Bethesda assay 
(inhibitor assay)7 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-rFIXFc antibody7 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology7,8 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry7,9 
X 
X 
X 
X 
X 
X 
X 
X 
FIX activity7,10 
X 
X 
X 
X 
X 
X 
X 
X 
DNA-Based Testing11 
X 
 
 
 
 
 
 
 
QoL Questionnaires12 
X 
X 
X 
X 
X 
X 
X 
X 
Health Outcomes13 
X 
X 
X 
X 
X 
X 
X 
X 
Subject eDiary Review13  
X 
X 
X 
X 
X 
X 
X 
X 
<<<<<<<<<<<<<<<<<<<<<< Ongoing >>>>>>>>>>>>>>>>>>> 

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Tests and Assessments1 
Visit 12 
 
Visit 2 
Month 6 
(±2 weeks) 
Visit 3 
Month 12 
(±2 weeks) 
Visit 4 
Month 18 
(±2 weeks) 
Visit 5 
Month 24 
(±2 weeks) 
Visit 6 
Month 30 
(±2 weeks) 
Visit 7 
Month 36 
(±2 weeks) 
Visits Semi-
Annually (Every 
6 months) 
(±2 weeks) 
to Individual Bleeding Episodes 
Treated in Clinic 
Response to the Treatment Regimen 
X 
X 
X 
X 
X 
X 
X 
X 
HJHS14 
X 
 
X 
 
X 
 
X 
X 
AE/SAE Monitoring and Recording 
X 
Monitor and record  at all visits; telephone call every 2 months for AE/SAE assessments 
Concomitant Therapy/Procedures 
Recording 
X 
Monitor and record at all visits; telephone call every 2 months 
AE=adverse events; HJHS=Hemophilia Joint Health Score; QoL=quality of life; SAE-serious adverse events  
Table footnotes are presented on page 24. 

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Table 1: 
Screening and Treatment Period, continued: 
Tests and Assessments1 
Unscheduled Visit15 
Final Study Visit/Early 
Termination Visit 
Follow-Up16 
14 ( +7) days after last 
dose of study drug 
Physical Examination4 
 
X 
 
Vital Signs5 
X 
X 
 
Height 
 
X 
 
Weight 
 
X 
 
rFIXFc dosing/dispensation/accountability6 
X 
X 
 
Nijmegen-modified Bethesda assay (inhibitor assay)7 
 
X 
 
Anti-rFIXFc antibody7 
 
X 
 
Hematology7,8 
 
X 
 
Blood Chemistry7,9 
 
X 
 
FIX activity7,10 
 
X 
 
QoL Questionnaires12 
 
X 
 
Health Outcomes13 
 
X 
 
Subject eDiary Review13  
X 
X 
 
Bleeding Episodes Treated in Clinic 
<<<<<<<< ongoing >>>>>>>> 
 
 to the 
Treatment Regimen 
X 
X 
 
HJHS14 
 
X 
 
AE/SAE Monitoring and Recording 
Monitor and record at all visits; telephone call every 
2 months for AE/SAE assessments 
X 
Concomitant Therapy/Procedures Recording 
Monitor and record at all visits; telephone call every 
2 months  
X 
AE=adverse events; HJHS=Hemophilia Joint Health Score; QoL=quality of life; SAE-serious adverse events  
Table footnotes are presented on page 24. 

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Footnotes for Screening and Treatment Period 
1. 
Subjects who enroll into 9HB01EXT will be assessed only for those parameters at had been previously assessed in the parent study. 
2. 
The End of Treatment (EOT) visit for the parent study may serve as the Screening Visit for the extension study.  Written informed consent and subject assent, if 
applicable, for participation in the extension study must be obtained at this visit before any extension study-related procedures are conducted.  The subject or his 
Parents/legal guardians should receive the informed consent information prior to this visit to allow adequate time for review at home, and discussion with the 
Investigator.  Data on medical history, demographics, screening tests, ongoing adverse events and concomitant therapy, and EOT tests and assessments will be 
transferred from the parent rFIXFc study, so it will not be necessary to repeat these assessments at Visit 1.  An HJHS or modified HJHS assessment, as appropriate, 
should be performed at Visit 1 in ALL subjects.  Study eligibility must be verified prior to study enrollment.  Subjects who enroll with a gap of greater than 37 days 
following the EOT Visit for the previous study should have all laboratory assessments performed and reviewed by the Investigator at Visit 1, prior to dosing with 
rFIXFc, to assess safety and inclusion/exclusion parameters.  The time allotted for Visit 1 may span a sufficient interval to allow for laboratory results to be reviewed and 
confirmed as suitable by the Investigator.  Otherwise, more than 1 clinic visit may be required prior to dosing with rFIXFc. 
3. 
Medical and surgical history includes any significant medical condition and/or any significant surgical histories that occurred prior to the subject enrollment in the parent 
study. 
4. 
Physical examination will include assessments of the skin, head, eyes, ears, nose, throat (HEENT), lymph, neck, chest/lungs, heart, vascular system, abdomen, 
musculoskeletal and neurological function, extremities, and joints.  Following Visit 7, physical examination will be performed on an annual basis. 
5. 
Vital signs assessments include blood pressure, pulse rate, respiratory rate and temperature (°C), and should be taken after the subject has been resting supine for 5 
minutes.  At dosing visits, vital signs should be measured pre-injection and post-injection.  
6. 
Subjects will receive supplies of rFIXFc for home administration from the study site at and between visits; each time, the study site staff will perform full medication 
exchange and accountability with the subject 
.  See Section 16 for information on planning and the dispensation process, and on supply 
accountability. 
7. 
To be performed at the central laboratory.  For FIX inhibitor and anti-rFIXFc antibody testing, a washout of at least 72 hours is recommended.  For subjects who have 
fewer than 50 exposure days (EDs) with rFIXFc following completion of Visit 1, a visit may be conducted to perform inhibitor testing at the time subjects reach 10 to 
15 EDs, 50 to 75 EDs, and after 100 EDs, as applicable (The total exposure day count[ED] is the number of rFIXFc exposure days from the previous rFIXFc study and 
this extension study, combined).  If the timing for inhibitor testing does not coincide with a scheduled visit, an unscheduled visit may be conducted.  Blood samples will 
be collected at each visit for back-up and archiving for future testing (if required) of immunology or further coagulation assays, or for clarification of any clinical or 
laboratory AE.  Additional inhibitor and anti-rFIXFc antibody testing should also be performed when deemed clinically relevant. 
8. 
Hematology includes:  white blood cells (WBC), differential, platelet count, hemoglobin, and hematocrit. 
9. 
Blood chemistry includes:  Electrolytes (sodium, potassium, chloride), glucose, total protein, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and serum creatinine. 
10. For weekly, individualized, and personalized prophylaxis regimens:  FIX activity is to be measured at the trough immediately prior to the infusion and at peak (recovery) 
30 (±5) minutes from the start of injection.  For on-demand treatment:  FIX activity should be measured at the discretion of the Investigator. 
11. The collection of a sample for DNA-based testing is optional and may occur at any time during the study, not exclusively at Visit 1. 
12. Patient-reported outcomes should be completed only if they were conducted during the parent study.  Questionnaires should be completed every 6 months, at scheduled 
clinic visits.  Questionnaires will be provided under a separate cover. 
13. Changes in patient-reported health outcomes assessed during the parent study are to be queried 
electronic patient diary (eDiary) on an ongoing basis, and 
details are to be recorded in the electronic case report form (eCRF). 

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14. Subjects entering the extension study from 998HB102 should continue to use the Modified Hemophilia Joint Health Score.  Subjects entering the extension study from 
9HB02PED should continue to use the HJHS Version 2.1.  Subjects entering the extension study from other parent studies should continue to use the Joint Health Score 
instrument that is consistent with his parent study.  Following Visit 7, the HJHS assessment will continue to be performed annually.  The HJHS assessment is not 
required at the Final Study Visit if it was performed within the last 9 months. 
15. Unscheduled visits may be necessary during the study, as determined by the Investigator, for reasons that may include repeating safety assessments, repeating blood 
sampling, testing FIX activity levels if required, or changing dose/regimen.  For subjects from a parent study who undergo surgery and enter the extension study before 
completing their Last Post-Operative Visit, an unscheduled visit may be conducted to perform the Last Post-Operative Visit assessments when the subjects switch from 
their post-surgery dosing regimen to a regimen outlined in Section 5.3.2 (see Section 5.3.3 for list of assessments).  Inhibitor testing will be performed at the time 
subjects reach 10 to 15 EDs, 50 to 75 EDs, and after 100 EDs, as applicable (The total ED is the combined rFIXFc exposure days from a previous rFIXFc study and this 
extension study).  If the timing for inhibitor testing does not coincide with a scheduled visit, an unscheduled visit may be conducted. 
16. A follow-up telephone visit is required 14 (+7) days after the last dose of study rFIXFc to monitor AEs, SAEs, and concomitant medications and therapies.  This 
14 (+7) day follow-up visit is not required if a subject ends his participation in the extension study to enroll into another rFIXFc study, however, a final visit/early 
termination visit is required. 

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4.2. 
Surgery Visits 
Table 2: 
Surgery Visits 
Tests and Assessments1 
Pre-Surgery2 
Visit 1 
Week -12 to 
Week -1 prior to 
Surgery 
Visit 2 
Day of Surgery 
 
Visit 3 
1-2 Weeks Post 
Surgery3 
 
 
Visit 4 
Last Post-
Operative Visit4 
 
Physical Examination5 
X 
X 
 
X 
Weight 
X 
X 
X 
X 
Vital Signs6 
X 
X 
X 
X 
Hematology7 
X 
X 
X 
X 
Blood Chemistry7  
X 
X 
X 
X 
Response8 
<<<<<<<<         ongoing as applicable       >>>>>> 
Investigator/Surgeon Assessment of 
Hemostatic Response9 
 
X 
 
 
FIX activity10 
X 
X 
X 
X 
Nijmegen-modified Bethesda assay 
(inhibitor testing)4 
X 
X 
X 
X 
Anti-rFIX Antibody Assay4 
X 
X 
X 
X 
rFIXFc Administration 
X 
X 
X 
X 
AE/SAE Monitoring and Recording  
X 
X 
X 
X 
Concomitant 
Medications/ Procedures Recording 
X 
X 
X 
X 
AE=adverse events; SAE-serious adverse events  
Footnotes for Surgery Visits 
1. 
All tests and assessments should be collected for major surgery and for minor surgery when available.  Subjects 
may be allowed to have a PK evaluation performed by the central or local laboratory prior to surgery if needed, in 
the opinion of the Investigator. 
2. 
To be assessed prior to surgery. 
3. 
Visit 3 (1-2 Weeks Post Surgery) and Visit 4 (Last Post-Operative Visit) are not performed for subjects who 
undergo minor surgery.  For major surgery, Visit 4 occurs when the subject returns to a regular rFIXFc regimen as 
determined by the Investigator, and is not required if the return to a regular rFIXFc regimen occurs at Visit 3. 
4. 
For surgery, inhibitor and anti-rFIXFc antibody testing is to be performed 2 to 4 weeks prior to surgery, pre-
operatively on the day of surgery, 1-2 weeks after surgery, and at the last post-operative visit.  For FIX inhibitor 
and antibody testing, a washout of at least 72 hours is recommended.  For minor surgery, the testing is performed 
 
5. 
Physical examination will include assessments of the skin, head, eyes, ears, nose, throat (HEENT), lymph, neck, 
chest/lungs, heart, vascular system, abdomen, musculoskeletal and neurological function, extremities, and joints.  
Following Visit 7, physical examination will be performed on an annual basis. 
6. 
Vital signs assessments include blood pressure, pulse, respiratory rate and temperature (°C), and should be taken 
after the subject has been resting supine for 5 minutes.  At dosing visits, vital signs should be measured pre-
injection and post-injection.  
7. 
To be performed at the central laboratory.  Hematology includes:  WBC, differential, platelet count, hemoglobin, 
and hematocrit.  Blood chemistry includes:  Electrolytes (sodium, potassium, and chloride), glucose, total protein, 
total bilirubin, ALT, AST, ALP, BUN, and serum creatinine. 

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8.
Subjects who require post-operative rFIXFc treatment for a bleeding episode at home will record their assessment 
of the response to treatment in the eDiary; this assessment is to be made approximately 8 to 12 hours from the 
time the rFIXFc injection was given to treat the bleeding episode and prior to any additional doses of rFIXFc 
given for the same bleeding episode. 
9. 
during surgery using a 
4-point scale.  This assessment will be done 24 hours after surgery.  See Appendix C and Appendix E. 
10. 
FIX activity levels should be measured prior to administration of the pre-operative (loading) dose of rFIXFc, and 
at 30 ±5 minutes post-dosing.  A repeat sample may be taken approximately 6 to 9 hours after the loading dose or 
at an interval based on the local standard of care for subsequent rFIXFc dosing.  
hospitalization, FIX activity will be measured daily at the local laboratory, and a plasma aliquot will be prepared 
for each blood sample for subsequent analysis at the central laboratory. 
 

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5. 
INTRODUCTION  
9HB01EXT is an extension study designed to assess the long-term safety and efficacy of rFIXFc 
in previously treated subjects with hemophilia B.  Male subjects of all ages who have completed 
any parent study with rFIXFc (998HB102, 9HB02PED, and any other rFIXFc study) may be 
eligible for enrollment in this study. 
The guideline on clinical investigation of recombinant and human plasma-derived factor IX 
products [EMA (EMA/CHMP/BPWP/144552/2009) 2011] was followed in the development of 
this protocol. 
5.1. 
Profile of Previous Experience 
Hemophilia B, or Christmas disease, is caused by a deficiency of functional clotting Factor IX 
(FIX).  This recessively inherited coagulation disorder is due to an X-chromosome mutation 
carried by females and expressed mainly in males, which affects approximately 1 in 50,000 
births worldwide [Skinner 2012].  A deficiency of FIX results in 
bleeding into joints, 
soft tissue, and muscle that can be associated with trauma or can occur in the absence of trauma 
(spontaneous bleeding).  Depending on the severity of the bleeding, it can also pose a life-
threatening situation (e.g. intracranial hemorrhage, other internal bleeding) for a subject if not 
treated appropriately.  FIX, a serine protease, and factor VIII, a cofactor for FIX, work in concert 
to activate Factor X; this activation is a central step in the clotting cascade. 
5.1.1. 
Therapies for Hemophilia B 
There is no available cure for hemophilia B, so treatment focuses on the replacement of FIX with 
FIX-containing coagulation products, administered intravenously (IV), to promote clotting.  The 
goal of treatment with FIX-containing coagulation products is to raise the circulating level of 
FIX to the lowest effective dose to achieve either resolution of bleeding (on-demand [episodic] 
treatment) or prevention of bleeding (prophylaxis treatment) [Roberts 1993; WFH 2005; 
MASAC March 2009].  The frequency of administration of FIX products differs among subjects 
and is usually tailored to the 
bleeding episode, frequency of bleeding, and goal of treatment for the subject.  The dose of FIX 
required also varies and is based on ongoing clinical experience and guidelines established by 
organizations such as the National Hemophilia Foundation of the United States and the WFH 
[Roberts 1993; Srivastava 2013] . 
The use of FIX-containing, plasma-derived coagulation products, available for almost 40 years, 
has led to vast improvements in the care of hemophilia B, subject life expectancy, and quality of 
life for people with hemophilia.  Risks of plasma-derived products include subject infection with 
serious blood-borne pathogens, including human immunodeficiency virus (HIV) and hepatitis B 
and C, as well as thrombosis.  Recombinant coagulation products with no animal- or human-
plasma-derived proteins, developed more recently, have the safety advantage that the risk of 
disease transmission is minimal [Roth 2001; White 1998]. 

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Identified priorities for hemophilia B therapy include the development of more convenient 
dosing options [Lambert 2007] and investigation into modified FIX agents with a longer half-life 
to decrease injection frequency.  Current therapy is focused on home therapies, which, taken 
prophylactically or administered at the onset of a bleeding episode, reduce short-term disability 
and long-
independence [Colvin 2008]. 
5.1.2. 
rFIXFc 
rFIXFc (BIIB029) is a recombinant coagulation Fc fusion protein, comprised of FIX covalently 
attached to the Fc domain of human IgG, that is in development as a long-acting version of rFIX 
for the treatment of hemophilia B.  rFIXFc has been tested in 14 subjects with severe, previously 
treated hemophilia B in a Phase 1/2a study and 123 subjects aged 12 years and older in a 
completed Phase 3 study (998HB102).  Another Phase 3 study is currently ongoing in pediatric 
subjects (9HB02PED).  Preclinical and clinical experience, to date, has shown an extended half-
life of FIX activity compared with commercially available recombinant FIX products.  This 
extended half-life may reduce the frequency of IV injections required for prevention of bleeding 
and for treatment for bleeding episodes in hemophilia B subjects.  A therapy with these 
characteristics may also improve treatment compliance and quality of life. 
5.1.3. 
Summary of Clinical Experience with rFIXFc 
Completed study SYN-FIXFc-07-001 was a Phase 1/2a, open-label, multicenter, safety, 
dose-escalation study evaluating the safety and PK of a single dose of rFIXFc in 14 adult male 
 
endogenous FIX).  In this study, rFIXFc was given in escalating doses at 6 dose levels, ranging 
from 12.5 to 100 IU/kg.  In this dose range, a dose-linear PK profile and a prolonged rFIXFc of 
t1/2 were demonstrated. 
A single dose of rFIXFc, ranging from 1 to 100 IU/kg, was demonstrated to be safe and well 
tolerated in the study population.  Adverse events were distributed evenly across treatment 
groups, and were mostly mild and not related to treatment.  Two serious adverse events (SAEs) 
occurred, depression and abdominal adhesions; neither event was considered related to the study 
drug, and both were resolved with treatment.  No deaths were reported during the study.  
Increased thrombin-antithrombin complex (TAT) levels in 2 subjects were not considered to be 
related to the study drug, but rather, to a minor ex vivo perturbation.  None of the subjects tested 
positive for FIX inhibitors or anti-FIXFc antibodies at any time during the study.   
In addition, a Phase 3 study in previously treated subjects aged 12 years or older with severe 
hemophilia B was recently completed (Study 998HB102).  A total of 123 subjects in the Phase 3 
study received rFIXFc as prophylaxis or on-demand treatment, and/or for perioperative 
management during the study.  Of the 123 subjects evaluated in the Phase 3 study, 115 were 
treated for at least 26 weeks and 56 were treated for at least 52 weeks.  There was a reduction in 
annualized bleeding rate (ABR) of 83% for subjects in the fixed weekly prophylaxis arm and a 
reduction of 87% for subjects in the individualized interval prophylaxis arm, compared to the 
on-demand treatment arm, and based on a negative binomial model. 

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Compared with BeneFIX®, rFIXFc demonstrated an improved PK profile.  The geometric mean 
elimination t½ of rFIXFc of 82.12 hours was 2.43-fold longer (p<0.001) than that of BeneFIX at 
33.77 hours.  Consistent with the prolonged t½, the mean residence time (MRT) of rFIXFc was 
2.39-fold longer (p<0.001) than BeneFIX, resulting in a 2.21-fold extension of Time to 1% 
trough (p<0.001) for rFIXFc, compared with BeneFIX. 
rFIXFc was well tolerated in the Phase 3 study.  No subject developed FIX inhibitors.  Common 
AEs observed were consistent with those expected in patients with hemophilia B.  Adverse drug 
reactions were mild and manageable, and the majority were not treatment limiting.  Two subjects 
(1.6%) were reported to have discontinued from the study due to AEs:  One subject required 
surgery for an infected knee prosthesis (device-related infection) and the other subject suffered 
injuries in a motorcycle accident (road traffic accident).  Both were considered unrelated to 
rFIXFc treatment.  There were no allergic reactions of Grade 2 or greater or serious vascular 
thrombotic events.  One SAE, obstructive uropathy, was assessed by the Investigator as possibly 
related to treatment with rFIXFc.  The event resolved with hydration and the subject completed 
the Phase 3 Study (998HB102). 
Study 9HB02PED (referred to as the pediatric study) is an open-label, multicenter study 
evaluating the safety, PK, and efficacy of rFIXFc in previously treated pediatric patients with 
severe hemophilia B, who are <12 years of age, and have at least 50 EDs to FIX products prior to 
enrollment.  Approximately 26 male subjects (13 subjects <6 years of age and 13 subjects 6 to 
<12 years of age) are planned to complete at least 50 weeks of prophylactic treatment to attain at 
least 50 EDs.  At least 20 of these subjects (10 subjects <6 years of age and 10 subjects 6 to 
<12 years of age) will undergo an evaluation of the PK profile of pre-study FIX and rFIXFc.  
Subjects who complete this study will be offered enrollment into the extension trial described in 
this protocol. 
For further details regarding the clinical studies conducted with rFIXFc, please refer to the 
. 
5.2. 
Study Rationale 
The results of the non-clinical data [Peters 2010], the Phase 1/2a study, and the Phase 3 study 
(998HB102) support further investigation of long-term repeat administration of rFIXFc in the 
prevention and treatment of bleeding episodes in hemophilia B subjects.  This extension study 
will evaluate the long-term safety and efficacy of rFIXFc in subjects with hemophilia B and will 
allow subjects from the Phase 3 (998HB102) pivotal study, from the pediatric study 
(9HB02PED), and from other rFIXFc studies to continue treatment with rFIXFc. 
5.3. 
Rationale for Dose and Schedule Selection 
Subjects 12 years of age or older will follow a weekly, individualized, or personalized 
prophylaxis regimen or will be treated on-demand, based on the clinical profile of the subject and 
by the trough and/or peak (recovery) values, if needed.  Subjects 12 years of age or older are 
allowed to change treatment regimens (for example, from prophylaxis to on-demand, or from 
on-demand to prophylaxis) during the course of the study.  Subjects less than 12 years of age will 

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receive a prophylactic regimen and will not have the option to change to on-demand treatment 
until he reaches the age of 12 years.  All treatment regimen changes will be discussed with the 
subject (and parent/guardian, as applicable).  All treatment regimen changes require the approval 
of the Sponsor Medical Monitor.  Details (including date of change, new dose and/or dosing 
interval, and reasons for the change) will be recorded on electronic case report forms (eCRFs). 
his parent rFIXFc 
study.  In the completed Phase 3 study, 998HB102, doses between 20 IU/kg and 100 IU/kg were 
administered.  In the pediatric study (9HB02PED), a starting dose of approximately 50 IU/kg to 
60IU/kg is being administered, with dose and interval adjustments up to 100 IU/kg twice a week, 
if necessary to maintain adequate FIX activity trough levels and prevent spontaneous bleeding 
events. 
5.3.1. 
On-demand (Episodic) Treatment 
The individual dose of rFIX
condition, type and severity of the bleeding event, and if indicated, FIX levels.  
pharmacokinetic (PK) profile and dosing levels from the parent study may also be used to guide 
dosing decisions.  Subjects <12 years of age, entering from another rFIXFc study, will not be 
offered this option, but can opt to receive on-demand treatment when they reach the age of 12 
years during the study. 
Please refer to Appendix A for guidance on dosing decisions. 
5.3.2. 
Prophylaxis Regimens 
The Investigator may consider the following options for prophylaxis to target a FIX trough of up 
to 5%, but is encouraged to use the lowest effective dose targeting a FIX trough level between 
1% and 3%.  If bleeding episodes occur at FIX trough levels of 1% to 3%, further adjustments to 
dose or interval over the course of the study will target trough levels of up to 5%.  In pediatric 
subjects  <12 years of age, doses may be adjusted up to a maximum prophylactic dose of 
100 IU/kg, with the interval decreased to twice a week, if necessary to maintain adequate FIX 
activity trough levels and prevent spontaneous bleeding events.  Details for each dosing option, 
including, if applicable, the date of change, new dose and/or dosing interval, and reason(s) for 
the regimen change, will be recorded on the appropriate eCRF each time a change is made. 
Option 1:  Weekly Prophylaxis  
Dosing is approximately 20 IU/kg to 100 IU/kg every 7 days.  The dose should be based on the 
 parent rFIXFc study and his individual pharmacokinetic 
profile (PK), trough, and/or peak (recovery) values. 
 Option 2:  Individualized Prophylaxis 

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Dosing is approximately 100 IU/kg every 8 to 16 days, or 2 times per month.  The dosing 
 parent rFIXFc study, and 
his individual PK, trough, and/or peak (recovery) values. 
 Option 3:  Personalized Prophylaxis 
If optimal prophylaxis dosing cannot be achieved using either of the above options, the 
Investigator may further personalize dosing to meet the needs of individual subjects. 
The Investigator may consider the following personalized dosing options: 
o 
.   
o Targeting a FIX trough level of >5%, if warranted by the bleeding history and/or 
activity level.   
o Dosing 2 times per week, e.g.  25 IU/kg, twice weekly, vs. 50 IU/kg, once weekly, for 
subjects who may have better control with such a regimen.  For pediatric subjects <12 
years of age, the dose may be adjusted up to 100 IU/kg twice weekly. 
The Investigator is not limited to the options above, and should consult the Medical Monitor for 
.  The personalized prophylaxis dosing option 
will require consultation with the Medical Monitor. 
Details for each dosing option, including, if applicable, date of change, new dose and/or dosing 
interval, and reason(s) for the regimen change will be recorded on the appropriate eCRF each 
time a change is made. 
5.3.3. 
Surgery and Rehabilitation 
If a subject requires emergent or elective surgery while participating in this study, he may be 
treated with the dose and regimen of rFIXFc deemed appropriate for the type of surgery.  All 
major surgeries will be reported as SAEs. 
All major surgical procedures must take place in a center that can provide study treatment, 
trained study personnel, post-operative assessments, and hematological consultation by the 
Investigator or Sub-Investigator.  If the surgery does not occur in such a setting, the subject will 
be withdrawn from the study.  See Section 10.1.3 for provisions for when a subject requires 
major surgery. 
If surgery-related dosing is continued during post-operative rehabilitation and/or physical 
therapy, the dose of rFIXFc will be adjusted to achieve a trough at a sufficient level to maintain 
hemostasis. 
Subjects will return to a regular rFIXFc regimen once all dosing for the post-operative 
rehabilitation period has been completed.  For subjects undergoing major surgery, a visit is 
required 1-2 weeks after surgery (Visit 3).  Visit 4 (Last Post-Operative Visit) occurs when the 

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subject returns to a regular rFIXFc regimen, as determined by the Investigator, and is required 
only if the subject did not return to a regular rFIXFc regimen at Visit 3.  For minor surgery, 
Visits 3 and 4 are not performed. 
(i.e., the pre-surgery dose).  This is the pre-operative period of the surgery.  The intra-operative 
period is defined as the time the surgery begins, to the time the surgery completes.  The 
post-operative care period is defined as the time period following the completion of the surgery 
through the last dose of rFIXFc given for the surgery, as judged by the Investigator/Surgeon, 
including doses given to prevent bleeding during the post-operative rehabilitation period. 
For subjects from a parent study who undergo major surgery and enter the extension study before 
completing their Last Post-Operative Visit from the prior rFIXFc study, an unscheduled visit 
may be conducted to perform the Last Post-Operative Visit assessments when the subjects switch 
from their post-surgery dosing regimen to a regular rFIXFc regimen (as outlined in 
Sections 5.3.1 and 5.3.2).  The following assessments must be performed at that time: 
 Physical examination 
 Vital signs (blood pressure, pulse, respiratory rate and temperature [°C]) 
 Weight 
 Hematology 
 
 
 FIX activity (to be measured at trough immediately prior to the injection and at peak 
[recovery] 30 [±5] minutes from the start of injection) 
 Subject eDiary review 
 Nijmegen-modified Bethesda assay (inhibitor assay) 
 rFIXFc administration and accountability 
 AE/SAE monitoring and recording  
 Concomitant therapy/procedures recording 
5.4. 
Potential Risks and Benefits 
benefits of rFIXFc. 

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6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1. 
Objectives  
6.1.1. 
Primary Objective 
The primary objective of the study is to evaluate the long-term safety of rFIXFc in subjects with 
hemophilia B. 
6.1.2. 
Secondary Objective 
The secondary objective of this study is to evaluate the efficacy of rFIXFc in the prevention and 
treatment of bleeding episodes in subjects with hemophilia B. 
6.2. 
Endpoints 
6.2.1. 
Primary Endpoint 
The primary endpoint is the occurrence of inhibitor development. 
6.2.2. 
Secondary Endpoints 
The secondary endpoints are as follows: 
 The annualized number of bleeding episodes per subject 
 The annualized number of spontaneous joint bleeding episodes per subject 
 The total number of days of exposure per subject per year 
 The consumption of rFIXFc as total dose per kg per subject per year 
 
the subject
response to his treatment regimen 
using a 4-point scale 
 Subject
 assessment of response to the treatment of bleeding episodes 
using a 4-point scale 
6.2.3. 
Major Surgery Endpoints 
The major surgery endpoints are as follows: 
 Investigator/Surgeon assessment of hemostatic response to surgery using the 4-point 
bleeding response scale 

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Number of injections and dose per injection to maintain hemostasis during the 
surgical period 
 Estimated blood loss (mL) during surgery and the post-operative period 
 Number of blood product units transfused during surgery 
6.2.4. 
Patient-Reported and Health Outcomes Endpoints 
Subjects will be assessed only for those health outcomes and quality of life parameters that had 
been previously assessed in the parent study, and only for as long as they remain within the age 
range for the respective instrument.  If a subject goes outside of the age range for a 
questionnaire, the subject should no longer complete it.  The Investigator will administer the age-
appropriate questionnaire at the appropriate visits.  The patient-reported outcomes and health 
outcomes assessed may include the following:  
Quality of Life (QoL) questionnaires: 
 Haem-A-QoL [von Mackensen & Gringeri 2009] 
 Haemo-QoL [von Mackensen 2004] 
 Hemo-Sat-Patient Satisfaction Scale for parents/guardians, Version 15 [MAPI 
Research Institute 2009] 
 Canadian Hemophilia Outcomes-
CHO-KLAT) 
o Children, Version 2.0 (for children previously enrolled in study 9HB02PED 
who are less than 18 years of age). 
o Proxy, Version 2.0p (for parent/guardian of children who were previously 
enrolled in study 9HB02PED and who are less than 18 years of age) 
 EQ-5D-Y [EQ-5D-Y 2011] 
 EQ-5D-3L [EuroQol 1990] 
Other patient-reported outcomes and health outcomes related to hemophilia 
 Number of hospitalizations, excluding planned hospitalizations, elective surgery 
documented at Visit 1, and emergent surgery 
 Number of emergency room visits  
 Number of physician visits, excluding study visits 
 Number of hospitalization days  

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Number of days off work, school/daycare, or preschool 
 Number of days off work for the parent/guardian or caregiver. 
 

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7. 
STUDY DESIGN 
7.1. 
Study Overview 
This is an open-label, multi-center, long-term study of intravenous (IV) administration of rFIXFc 
in previously treated patients (PTPs) with hemophilia B who have completed the Phase 3 pivotal 
study (998HB102), the pediatric study (9HB02PED), or any other study with rFIXFc.  This is a 
global study and will be offered to all sites participating in these studies.   
Based on estimated sample sizes from the parent studies, approximately 100 subjects from the 
completed Phase 3 study (998HB102) and approximately 20 subjects from the ongoing pediatric 
study (9HB02PED) may be eligible to enroll in this extension study.  Additional subjects may 
transition from other rFIXFc studies into this extension study in the future.  The End of 
Treatment (EOT) Visit from the previous study may serve as the screening visit for the extension 
study.  Assessments performed at this visit will be used to confirm eligibility for participation in 
the extension study.    
Study visits are scheduled at 6-month (±2 weeks) intervals following completion of Visit 1.  
Unscheduled visits may occur as deemed necessary by the Investigator.  For subjects who enter 
the extension study and undergo surgery before completing their Last Post-Operative Visit from 
the parent rFIXFc study, the Last Post-Operative Visit assessments will be performed when the 
subjects switch from their post-surgery dosing regimen to a regimen outlined in Section 5.3.2 
(see Section 5.3.3 for the list of assessments).  Inhibitor testing will be performed at the time 
subjects reach 10 to 15 EDs, 50 to 75 EDs, and after 100 EDs, as applicable.  The number of 
exposure days (EDs) for inhibitor testing is comprised of the number of exposure days from the 
parent study and this extension study, combined.  If the timing for inhibitor testing does not 
coincide with a scheduled visit, an unscheduled visit may be conducted. 
For subjects undergoing surgery, post-operative clinic visits may be more frequent.  For subjects 
undergoing major surgery, a visit (Visit 3) is required 1-2 weeks after surgery (Visit 3 is not 
required for minor surgery).  Visit 4 is required only if subjects who had major surgery did not 
return to a regular rFIXFc regimen at Visit 3.  All major surgeries will be reported as SAEs.  
Scheduled visits will include safety and efficacy assessments and FIX activity measurements to 
assess trough and peak (recovery) (Section 4).  In addition, the site will contact study subjects 
and/or caregivers by telephone on a bimonthly basis to review adverse events, treatment 
compliance, use of concomitant medications and therapies, and other issues. 
Treatment will be self-administered as weekly, individualized, or personalized prophylaxis, or as 
on-demand treatment.  Subjects 12 years of age or older will be able to switch from one regimen 
to another at scheduled or unscheduled visits during the study, per Investigator discretion.  
Subjects less than 12 years of age will receive a prophylactic regimen and will not have the 
option to change to on-demand treatment until they turn 12 years of age.  

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To ensure accuracy of FIX trough and/or peak (recovery) and inhibitor testing, subjects 
following a prophylaxis regimen should schedule clinic visits 72 hours after the previous dose of 
rFIXFc, whenever possible.   
Subjects are expected to be followed through at least 100 exposure days (EDs) to rFIXFc and 
may further continue in this study for up to 4 years or until rFIXFc is commercially available in 
the applicable participating country.    
7.1.1. 
Dose-Limiting Toxicity 
No dose-limiting toxicities have been identified to date in humans receiving a single dose of 
rFIXFc up to 100 IU/kg.  Also, no dose limiting toxicities were observed in preclinical animal 
studies where repeat doses of up to 1000 IU/kg were evaluated. 
Doses higher than 100 IU/kg may be used in this study, for instance, in surgery, to achieve the 
required FIX levels to prevent bleeding.  In pediatric subjects, the dose for routine prophylaxis 
and treatment of bleeding episodes may be adjusted up to 100 IU/kg at an interval no more 
frequent than twice weekly, although higher doses of up to 150 IU/kg may be used to achieve 
FIX activity to prevent bleeding.  However, the maximum dose during surgery will not exceed 
the predicted accumulated Cmax of approximately 150% of normal (normal ranges are 50-150% 
FIX activity). 
An overdose of rFIXFc is defined as any single dose >150 IU/kg (see Section 15.4.1). 
7.1.2. 
Inhibitor Testing 
If inhibitor development is suspected at any time during the study (for example, because the 
expected plasma FIX activity levels are not attained, or bleeding is not controlled as expected 
following dosing), inhibitor testing will be performed by the central laboratory.  The definition of 
a positive result for an 
separate samples, drawn approximately 2 to 4 weeks apart.  Both tests must be performed by the 
central laboratory using the Nijmegen-modified Bethesda assay. 
A high-titer inhibitor is de
, identified and confirmed on 2 separate samples 
drawn approximately 2 to 4 weeks apart.  Both tests must be performed by the central laboratory 
using the Nijmegen-modified Bethesda assay. 
When an inhibitor test is performed at the local laboratory, an aliquot sample must be sent in 
parallel to the central laboratory. 
For FIX inhibitor testing, a washout period of at least 72 hours is recommended. 
Inhibitor testing will be performed at the time subjects reach 10 to 15 EDs, 50 to 75 EDs, and 
after 100 EDs, as applicable.  The number of exposure days for inhibitor testing consists of the 
number of exposure days from the parent study and this extension study, combined.  If the timing 
for inhibitor testing does not coincide with a scheduled visit, an unscheduled visit may be 
conducted. 

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7.1.3. 
Anti-rFIXFc Antibody Testing 
Blood samples will be collected for back up and archiving for each subject at each inhibitor 
testing visit and may also be collected and archived at the time of any clinical event deemed 
relevant to rFIXFc antibody testing (see Table 1 and Table 2).  In order to detect and characterize 
non-neutralizing antibodies that may react with rFIXFc, samples will be subject to an exploratory 
assay that differentiates between antibodies with specificities for rFIXFc, FIX (plasma FIX or 
BeneFIX®), and Fc.  The electrochemiluminescent assay (ECLA) used for this test is 
approximately100-fold more sensitive than the Nijmegen-modified Bethesda assay.   
7.1.4. 
Bleeding Episodes 
If a subject experiences a bleeding event at any time during the study, he or his caregiver should 
follow the guidance for the treatment of bleeds, to be provided to each subject and/or caregiver.  
Guidance for study staff is provided in Appendix A.  The type of bleed and the dose required to 
stop the episode wi
eDiary, EPD). 
In this study, when a subject reports a bleed or hemorrhage, and is treated with study drug, it will 
be classified as either spontaneous or traumatic by the subject or the subject s caregiver.  The 
the study.   
In this study, a bleed will be defined as follows:  a bleeding episode starts from the first sign of a 
bleed and ends no more than 72 hours after the last treatment for the bleed, within which any 
symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, are 
considered the same bleed.  Any injection to treat the bleed, taken more than 72 hours after the 
preceding one, will be considered the first injection to treat a new bleed at the same location.  
Any bleeding at a different location is considered a separate bleed, regardless of time from last 
injection. 
Spontaneous bleeding episodes:  Bleeding episodes should be classified as spontaneous if a 
subject records a bleeding event when there is no known contributing factor such as definite 
trauma or antecedent strenuous activity.  
the Investigator.  Target joints can have spontaneous bleeding episodes.   
Traumatic bleeding episodes:  Bleeding episodes should be classified as traumatic if a subject 
records a bleeding event when there is a known or believed reason for the bleed.  For example, if 
a subject were to exercise strenuously and then have a bleed, even in the absence of any obvious 
injury, the bleed would be recorded as a traumatic bleed.  Target joint bleeding episodes can be 
traumatic if a known action led to bleeding into the joint. 
7.1.4.1. 
Information to be Recorded 
The occurrence of bleeding in this study will be obtained from eDiaries and any medical records 
generated while the subject is receiving study treatment.  
enter eDiary information in a timely manner to facilitate appropriate medical review and dosing 
guidance.  The clinical sites and study monitors will ensure that there is consistency between the 
.  During clinical visits and bi-monthly telephone calls with 

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the eCRF, documenting the new classification of the bleed according to the Investigator, and 
.  With regard to those 
. 
Bleeding episodes will not be reported as AEs; however, the concomitant events associated with 
a bleed may be reported as an AE, if appropriate (i.e., a fracture in an elbow).  Both spontaneous 
bleeding episodes and traumatic bleeding episodes will be collected.   
The following information will also be documented in the eDiary: 
 The type of bleeding episode (e.g., spontaneous, traumatic) 
 The date the bleeding episode occurred 
 The dose administered for the bleeding episode, including any repeat doses 
 The location of the bleed (joint, internal, skin/mucosa, or muscle) 
 The reason for administering the dose (medical or nonmedical reasons [e.g., strenuous 
activity or other reason]) 
7.1.4.2. 
Procedure to Treat the Bleeding Episode 
known PK information from the previous study or FIX trough and/or peak (recovery) 
measurements in this study, type and severity of the bleeding event (see Appendix A for 
guidance on dosing), and input from the Sponsor, if necessary. 
episode and with a single dose of rFIXFc.  Most bleeding episodes should resolve with a single 
dose of rFIXFc.  If a subject has one spontaneous bleed and the Investigator is concerned the 
trough level is too low, the Investigator should contact the Sponsor to discuss next steps for this 
subject.   
 If the bleeding episode stops with a single IV dose of rFIXFc, the subject should 
return to his previous dosing regimen and will be treated with his next dose of 
rFIXFc, as previously scheduled, even if this results in consecutive daily doses. 
 If the bleeding episode does not stop within 48 hours with the single IV dose of 
rFIXFc, the subject or the subject
caregiver should consult with the Investigator for 
an optimal rFIXFc dose and dosing interval.  Because of the long lasting effect of 

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rFIXFc, it is recommended that the subject takes the first follow-up dose no less than 
48 hours after the initial dose.  However, if the subject experiences persistent pain or 
other signs of ongoing bleeding, the first follow-up dose may be administered before 
48 hours.  Administration of the second dose of rFIXFc as a follow-up treatment will 
be determined by the Investigator, 
.  Please 
refer to Appendix A for rFIXFc dosing guidance.  Once the bleeding event stops, the 
subject will return to his previous dosing regimen and will be treated with his next 
dose of rFIXFc as previously scheduled, even if this results in consecutive daily 
doses. 
 If the bleeding event does not stop with 2 doses (initial and follow-up treatments) 
of rFIXFc, the subject or the subject s caregiver should contact the Investigator for 
advice.  Following consultation with the Investigator, a third dose of rFIXFc will be 
administered 48 hours after the administration of the second dose of rFIXFc.  The 
third dose (second follow-up dose) may be at the same dose level as the second dose 
.  
Please refer to Appendix A for rFIXFc dosing guidance.  Once the bleeding event 
resolves, the subject will return to his previous dosing regimen and will be treated 
with his next dose of rFIXFc as previously scheduled, even if this results in 
consecutive daily doses. 
 If the bleeding event still has not stopped after 3 doses (initial and 2 follow-up 
doses) of rFIXFc, the Investigator should contact the Sponsor Medical Monitor to 
discuss the next steps for treatment of the subject. 
7.1.4.3. 
Dose and/or Interval Modification Following Bleeding Episodes 
Dose and/or interval modification following bleeding episodes can occur if any subject 
experiences 
-month period.  The 
Investigator can adjust the rFIXFc dose, as follows: 
 If an increase is required, the dose may be increased in increments of at least 5 IU/kg. 
 The dose and/or interval may be adjusted after discussion with the Sponsor Medical 
Monitor. 
See Section 5.3 for a description of regimen changes. 
7.2. 
Overall Study Duration and Follow-Up 
The study period will consist of Screening and Treatment.  Subjects are expected to be followed 
through at least 100 exposure days (EDs) to rFIXFc and may further continue in this study for up 
to 4 years or until rFIXFc is commercially available in the applicable participating country.    

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7.2.1. 
Screening 
Subject eligibility for the study will be determined prior to enrollment (Visit 1).  The EOT Visit 
for the parent study may serve 
37 days 
following the EOT Visit of the parent study, all laboratory assessments for Visit 1 must be 
performed and eligibility confirmed prior to dosing with rFIXFc.   
Informed consent for the extension study may be reviewed and obtained during the EOT visit of 
the previous study, and if not, consent must be obtained at Visit 1 of the extension study. 
7.2.2. 
Treatment 
Eligible subjects will self-administer rFIXFc intravenously according to their assigned treatment 
regimen.  Caregivers or Sponsor-approved designees may also administer rFIXFc.  Where 
appropriate, rFIXFc may be administered in the clinic. 
7.2.3. 
Follow-Up 
A final study visit will be conducted approximately 14 (+7) days after treatment with the last 
dose of study drug rFIXFc.  This 14 day follow-up visit is not required if a subject ends his 
participation in the extension study to enroll into another rFIXFc study. 
7.3. 
Study Stopping Rules 
The Sponsor may terminate this study at any time, after informing Investigators.  Investigators 
will be notified by the Sponsor or designee if the study is placed on hold, completed, or closed. 
The study must be stopped in the following cases: 
 Three subjects develop a high titer (i.e.  
Section 7.1.2.  The number of subjects can be adjusted based on sample size when 
more subjects are included in this trial from other rFIXFc parent studies. 
 An unexpected, serious, or unacceptable risk to the study subjects. 
If the study is stopped, the events will be investigated, enrollment will be stopped, and current 
subjects will stop dosing with rFIXFc.  
Surveillance 
Team, it is determined that the study should be permanently discontinued, then subjects will 
attend a final visit. 
7.4. 
End of Study 
The end of study is when the last subject completes his last visit. 

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8. 
SELECTION OF SUBJECTS 
8.1. 
Inclusion Criteria 
To be eligible to participate in this study, candidates must meet the following eligibility criteria 
at the time of signing the informed consent at Visit 1 of the study, or at the EOT of the previous 
study.  The eligibility assessment must be documented. 
1. Ability to understand the purpose and risks of the study and ability to provide signed and 
dated informed consent and authorization to use protected health information (PHI) in 
accordance with national and local subject privacy regulations.  Parental or guardian 
consent is required for subjects who are less than 18 years of age or unable to give 
consent, or as applicable per local laws.  Subjects who are less than 18 years of age may 
provide assent in addition to the parental/guardian consent, if appropriate.  Written 
informed consent must be provided before any screening tests or assessments are 
performed. 
2. Subjects who have completed studies 998HB102, 9HB02PED, or other studies with 
rFIXFc. 
8.2. 
Exclusion Criteria 
Candidates will be excluded from study entry if any of the following exclusion criteria exist at 
the time of signing the informed consent at Visit 1 of the study, or at the EOT of the previous 
study: 
1. Confirmed high-
, as defined in Section 7.1.2. 
2. Current enrollment in any other clinical study. 
3. Inability to comply with study requirements. 
4. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make 
the subject unsuitable for enrollment. 

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9. 
ENROLLMENT AND REGISTRATION PROCEDURES 
9.1. 
Enrollment and Screening 
Adult subjects must provide written informed consent and pediatric subjects may provide written 
assent (as appropriate), before any screening tests or assessments are performed.  For subjects 
less than 18 years of age, or, for subjects otherwise unable to provide written informed consent, 
parents or legal guardian(s) must obtain the informed consent form and return to the clinic 
following review to discuss and sign the Consent/Assent forms, as appropriate.  At the time of 
consent/assent, the subject will be enrolled into the study.  This will occur following successful 
completion of the EOT assessments for the previous rFIXFc study.  Participating study sites are 
required to document all screened candidates initially considered for inclusion in this study.  If a 
source documents and on the screening log. 
9.2. 
Registration of Subjects 
Subjects will be registered at Visit 1 after all assessments for the EOT Visit of the previous 
rFIXFc study have been completed and after the Investigator has verified that they are eligible 
per criteria in Sections 8.1 and 8.2.  Subjects will retain their previous study identification 
number.  Subject identification numbers previously assigned will not be reused for another 
subject even if a subject does not receive treatment. 
Refer to the Study Reference Manual for details on registration. 
As confirmation, the Sponsor or designee will provide the Investigator with written verification 
email or fax. 
9.3. 
Blinding Procedures 
Not applicable.  This is an open-label study. 

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10. 
TREATMENT OF SUBJECTS 
The Sponsor will provide rFIXFc to the study sites via designated distributors. 
Refer to Section 12 (Study Treatment Management) for specifics on the preparation, storage, 
handling, disposal, and accountability of study treatment. 
10.1. 
Study Treatment Schedule and Administration 
Instructions for preparation and administration of rFIXFc are provided in the Drug Handling and 
Administration (DHA) Manual. 
rFIXFc will be administered over several minutes by slow intravenous (IV) injection.  The rate 
of administration should be determined by the subjec
.  Any missed doses should 
be taken as soon as possible or per the instructions of the Investigator. 
Subjects will follow either a weekly, individualized, or personalized prophylaxis or be treated 
on-demand 
parent rFIXFc study.  Subjects 12 years of age or older will be permitted to change from 
prophylaxis regimens to on-demand treatment, and from on-demand treatment to prophylaxis 
during this study.  Subjects less than 12 years of age will receive a prophylactic regimen and will 
not have the option to change to on-demand treatment until they reach the age of 12 years during 
the study. 
All treatment regimen changes will be discussed between the Investigator and the subject (and 
parent/guardian, as applicable).  All treatment regimen changes require the approval of the 
Sponsor Medical Monitor. 
10.1.1. 
Prophylaxis Regimens 
Prophylaxis treatment options may include weekly prophylaxis, individualized prophylaxis, or 
personalized prophylaxis.  A weekly prophylaxis regimen is comprised of rFIXFc doses of 
20 IU/kg to 100 IU/kg, administered once weekly.  Subjects on an individualized prophylaxis 
regimen are treated at doses and dosing intervals that are tailored based on their PK profiles and 
dosing levels from parent rFIXFc studies or FIX trough and/or peak (recovery) levels obtained 
during this extension study.  In pediatric subjects <12 years of age, the dose may be adjusted up 
to 100 IU/kg, with the interval decreased to twice weekly, if necessary to maintain adequate FIX 
activity trough levels and prevent spontaneous bleeding events.. 
The personalized prophylaxis dosing option will require approval from the Medical Monitor. 
Please refer to Section 5.3.2 for descriptions of prophylaxis dosing options. 

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10.1.2. 
On-demand (Episodic) Treatment 
condition and the type and severity of the bleeding event.  Please refer to Appendix A for on-
demand dosing guidelines.  Subjects less than 12 years of age entering from a parent rFIXFc 
study will not have the option of an on-demand treatment until they reach the age of 12 years 
during the study. 
10.1.3. 
Surgery 
For subjects who require emergent or elective surgery during the study period, the dose and 
regimen of rFIXFc shall be that deemed appropriate for the type of surgery to be performed. 
All major surgeries must take place in a center that can provide study treatment, trained study 
personnel, post-operative assessments, and hematological consultations by the Investigator or 
Sub-Investigator.  If the surgery does not occur in such a setting, the subject will be withdrawn 
from the study. 
In addition, subjects who require major surgery may receive rFIXFc if: 
1. The surgery occurs within the contracted Institution for the trial and/or a separate 
to data generated in the trial at an alternative Institution deemed appropriate by the 
Investigator. 
2. The Investigator and/or appropriate qualified/licensed delegate is available to: 
a. Administer all the rFIXFc doses required during surgery and during post-operative 
rehabilitation (if applicable). 
b. Provide medical oversight and guidance throughout the duration of the pre-operative 
and the intra-operative periods. 
Surgeries, elective or emergent, will be classified as major or minor, as follows: 
 Major surgery is defined as any surgical procedure (elective or emergent) that 
usually, but not always, involves general anesthesia and/or respiratory assistance, in 
which a major body cavity is penetrated and exposed, or a substantial impairment of 
physical or physiological functions is produced (e.g., laparotomy, thoracotomy, 
craniotomy, joint replacement, or limb amputation). 
 Minor surgery is defined as any surgical procedure (elective or emergent) that does 
not involve general anesthesia and/or respiratory assistance (e.g., minor dental 
extractions, incision, and drainage of abscess, joint or other injections, or simple 
excisions).   
All major surgeries will be reported as SAEs. 

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For major surgery, inhibitor and anti-factor rFIXFc antibody testing should be performed 2 to 4 
weeks prior to the scheduled surgery, pre-operatively on the day of surgery, 1-2 weeks post-
surgery (Visit 3), and at the last post-operative visit (Visit 4).  Visit 4 (Last Post-Operative Visit) 
occurs when the subject returns to a regular rFIXFc regimen, as determined by the Investigator, 
and is required only if the subject did not return to a regular rFIXFc regimen at Visit 3.  For 
minor surgery, the testing may be performed at the I
. 
On the day of surgery, subjects will be given a preoperative dose of rFIXFc as a bolus, and, in 
the case of emergency surgery, as soon as possible prior to the procedure.  Pre-dose FIX activity 
levels will be sampled, followed by FIX peak (recovery) samples, 30 (±5) minutes post-dosing.  
A repeat sample may be taken approximately 6 to 9 hours after the loading preoperative dose is 
administered or at an interval based on the local standard of care for determination of subsequent 
rFIXFc dosing.  
local laboratory and a plasma aliquot will be prepared for each blood sample drawn so that 
subsequent analysis at the central laboratory can be performed. 
Doses higher than 100 IU/kg may be used in the context of surgery to achieve the required FIX 
levels to prevent bleeding.  However, the maximum number of daily or every-other-day doses 
will not exceed the predicted accumulated Cmax of approximately 150% of normal (normal 
ranges are 50% to 150% FIX activity).  All surgical dosing plans will be discussed with and 
approved by the Sponsor Medical Monitor before surgery.  All doses administered in the hospital 
will be captured in the eCRF. 
Bleeding events caused directly by surgery should not be recorded, although undesired or 
unexpected bleeding during or after surgery should be recorded on the eCRF. 
10.2. 
Treatment Precautions 
Precautions should be taken with any FIX product. 
The subject will be provided with specific instructions on what to do in the event of an overdose, 
allergic reaction, bronchospasm, or anaphylaxis while at home, including how to seek emergency 
medical treatment. 
10.3. 
Modification of Dose and/or Treatment Schedule 
10.3.1. 
Prophylaxis Regimen 
Please refer to Section 5.3.2 for details on prophylaxis regimens. 
10.3.2. 
On-demand (Episodic) Treatment 
rFIXFc 
the type 
and severity of the bleeding episode, and in some cases, FIX peak (recovery) levels.  
PK profile and dosing levels from his parent study may also be used to guide dosing decisions. 
Specific guidance for treatment of bleeding episodes is presented in Appendix A. 

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10.4.
Treatment Compliance
Compliance with treatment dosing is to be monitored by site staff. 
Subjects will record both routine doses and doses for the treatment of bleeding episodes in the 
eDiary.  Diary data will be reviewed on a regular basis by site staff. 
10.5. 
Concomitant Therapy and Procedures 
10.5.1. 
Concomitant Therapy 
A concomitant therapy is any drug or substance administered from 30 days prior to Visit 1 until 
14 (+7) days after the last dose of rFIXFc in this extension study.  Concomitant medications, 
for eCRF completion.  Adverse events (AEs) related to administration of these therapies or 
procedures must be documented on the appropriate eCRF. 
10.5.1.1. Allowed Concomitant Therapy 
Investigator. 
Allowed therapies include treatment for hepatitis and/or HIV, routine immunizations, treatment 
with systemic steroids and/or inhaled steroids (with approval of the Sponsor Medical Monitor), 
and/or non-steroidal anti-inflammatory drugs (NSAIDs).  Acetylsalicylic acid is permitted only 
at a low dose (
 mg), with approval of the Sponsor Medical Monitor. 
All allowed therapies must be recorded in the eCRF. 
10.5.1.2. Disallowed Concomitant Therapy 
No other investigational drug may be used concomitantly with the study treatment. 
The following concomitant medications are not permitted during the study: 
 Acetylsalicylic acid doses >81 mg. 
 Current systemic treatment with chemotherapy and/or other immunosuppressant 
drugs (unless advised otherwise after consult with the Medical Monitor) 
 Any other FIX product (with exceptions listed in Section 11.1) 
10.5.2. 
Concomitant Procedures 
A concomitant procedure is any therapeutic intervention (e.g., surgery/biopsy, physical therapy) 
or diagnostic assessment (e.g., blood gas measurement, bacterial cultures) performed between 
the time the subject is enrolled in the study until the study is completed/terminated by the 
Sponsor, unless the subject is being followed for study-related toxicity. 

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eCRF, according to instructions for eCRF completion.  Adverse events (AEs) related to the 
administration of these therapies or procedures must be documented on the appropriate eCRF. 
10.6. 
Continuation of Treatment  
Subjects are expected to be followed through at least 100 exposure days (EDs) to rFIXFc and 
may further continue in this study for up to 4 years or until rFIXFc is commercially available in 
the applicable participating country.    

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11. 
WITHDRAWAL OF SUBJECTS FROM STUDY TREATMENT 
AND/OR THE STUDY 
11.1. 
Discontinuation of Study Treatment 
A subject must permanently discontinue rFIXFc for any of the following reasons: 
 A Grade 2 or greater allergic drug reaction in association with administration of 
rFIXFc, as defined below by the Recommendations for Grading of Acute and 
Sub-Acute Toxic Effects on the World Health Organization (WHO) scale [WHO 
handbook, 1979]: 
o Grade 2 
Bronchospasm related to rFIXFc; no parenteral therapy needed 
o Grade 3 
Bronchospasm related to rFIXFc; parenteral therapy required 
o Grade 4 
Anaphylaxis related to rFIXFc 
 A high-titer inhibitor (
), as defined in Section 7.1.2. 
 Use of FIX products other than rFIXFc, unless it occurs in one life-threatening 
emergency and/or as a result of one accidental use, and the Sponsor agrees to retain 
the subject in the study.  
the Investigator should contact the Sponsor Medical Monitor. 
 Any condition a subject develops that precludes him from complying with the study 
procedures.   
 The subject experiences a medical emergency that necessitates discontinuation of 
treatment. 
 Clinical judgment of the Investigator:  a subject may have treatment permanently 
discontinued if, 
to continue with the study treatment. 
 The parent or legal guardian can withdraw the subject from the study at will at any 
time. 
 The subject and/or his parent/guardian withdraw consent. 
 At the discretion of the Investigator or Sponsor for noncompliance. 
The reason for discontinuation 
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For any subject who no longer responds to treatment with rFIXFc, as determined by the 
Investigator, a decision will be made with the Sponsor whether to continue the subject on the 
study. 
Subjects who discontinue treatment should remain in the study to complete protocol-required 
tests and assessments, and then must be permanently withdrawn from the study. 
11.2. 
Withdrawal of Subjects From Study 
Subjects must be withdrawn from the study for any one of the following reasons: 
 The subject and/or parent/guardian withdraw consent. 
 The subject and/or parent/guardian are unwilling or unable to comply with the 
protocol 
 The subject meets any of the criteria defined in Section 11.1. 
 eCRF. 
Subjects who discontinue study treatment and are withdrawn from the study will not be replaced. 
If the decision is made to withdraw the subject from the study, the final study visit/early 
termination visit will be performed, as described in Section 4 (Table 1). 

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12. 
STUDY TREATMENT MANAGEMENT 
Please refer to the Directions for Handling and Administration (DHA) for full details regarding 
rFIXFc. 
The study treatment must be stored in a secure location.  Accountability for study treatment is 
the responsibility of the Investigator.  More details concerning this responsibility are included in 
Section 12.1.4.  Study treatment must only be dispensed by designated study staff.  Study 
treatment is to be dispensed only to subjects, to parents/legal guardians of subjects enrolled in 
this study, or to Sponsor-approved designees.  Once study treatment is dispensed to a subject, it 
can only be administered to that subject.  Study treatment vials are for one-time use only; any 
study treatment remaining in the vial should not be used for another subject. 
Study site staff should refer to the DHA located in the Study Reference Manual for specific 
instructions on the handling, preparation, administration, and disposal of the study treatment.  
The DHA supersedes all other references (e.g., Investigator
Brochure). 
The 
estigational site for dispensation of 
inventory.  This is to ensure that adequate drug supplies for treatment are maintained, including 
an adequate supply to treat breakthrough bleeding or due to delays in scheduling clinic visits. 
12.1. 
rFIXFc (BIIB029) 
rFIXFc is supplied in a kit that contains several components:  a vial of lyophilized drug, the 
diluent syringe, a filter device vial adapter, and a winged injection set.  The lyophilized powder 
is in a clear glass vial containing 250, 500, 1000, 2000, or 3000 IU of rFIXFc (nominal 
strengths).  Not all strengths may be available at the start of the study.  The drug product is 
reconstituted with a diluent syringe containing 5 mL of 
 sodium chloride.  After 
reconstitution of the lyophilized drug product, the concentrations of excipients for the 250, 500, 
1000, and 2000 IU/vial strengths are 
 L-histidine, 
 sucrose,
 mannitol,
 
polysorbate 20, and 
 sodium chloride.  The concentrations of excipients for the 
3000 IU/vial strength are
 L-histidine, 
 sucrose, 
 mannitol, 
 polysorbate 
20, and 
 sodium chloride. 
The label will be compliant with local labeling requirements. 
12.1.1. 
rFIXFc Preparation 
The individual preparing rFIXFc should first carefully review the instructions provided in the 
DHA (if site staff), or in subject information materials provided by the site. 
If the packaging is damaged, or if there is anything unusual about the appearance or attributes of 
the vials or drug, it should not be used.  The vial in question should be saved by the subject or 
site, and then immediately reported by the site to the Sponsor. 

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12.1.2. 
rFIXFc Storage 
Site stocks of rFIXFc kits should be stored at 2 C to 8 C in a monitored, locked refrigerator with 
limited access or the room in which the refrigerator resides must be locked and have limited 
access. 
12.1.3. 
rFIXFc Handling and Disposal 
The Investigator must return all unused vials/kits of rFIXFc as instructed by the Sponsor.  The 
instructions for return will be provided to the site at the time the request is made by the Sponsor. 
If the Sponsor requires the study site to destroy unused rFIXFc kits, the institution/Principal 
Investigator(s) must notify the Sponsor, in writing, of the method of destruction, the date of 
destruction, and the location of destruction. 
12.1.4. 
rFIXFc Accountability 
The study site must maintain accurate records, demonstrating dates and amount of study 
treatment received, to whom dispensed (subject-by-subject accounting), amount returned by the 
subject, and accounts of any study treatment accidentally or deliberately destroyed. 
for full medication exchange and accountability.  At the end of the study, reconciliation must be 
made between the amount of rFIXFc supplied, dispensed, and subsequently returned to the 
Sponsor.  A written explanation must be provided for any discrepancies. 

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13. 
EFFICACY ASSESSMENTS 
Subjects that enroll into this study will be assessed only for those parameters that had been 
previously assessed in the parent study.   
13.1. 
Clinical Efficacy Assessments 
 
The following clinical tests/assessments will be performed to assess the efficacy of rFIXFc. 
For all subjects: 
 Number of bleeding episodes reported by each subject 
during the study period 
o Recording of bleeding episodes in the hospital in the eCRF by the 
Surgeon/Investigator; recording of all other bleeding episodes in the eDiary by 
the 
caregiver 
 Dose and dosing interval adjustments 
 Assessment of response to treatment using a 4-point scale in the eDiary (Appendix C) 
o Assessment of response to bleeding episodes using a 4-point scale by the 
Investigator for individual bleeding episodes treated in the clinic; assessment 
of all other bleeding episodes in the eDiary by the 
caregiver 
 
using a 
4-point scale (Appendix D) 
For subjects undergoing surgery, in addition to the above  
 Investigator/Surgeon assessment of hemostatic response using the 4-point bleeding 
response scale (Appendix E)  
 Number of injections and dose per injection to maintain hemostasis during the 
surgical period 
 Number of blood product units transfused during surgery 
 Estimated blood loss (mL) during surgery and the post-operative period 
Refer to Section 4 for the timing of assessments. 

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13.2.
Laboratory Efficacy Assessments
The following laboratory tests/assessments will be performed to assess the efficacy of rFIXFc: 
 FIX activity, peak (recovery) and/or trough measurements, if applicable (determined 
by the one-stage aPTT clotting assay performed at the central laboratory) 
Refer to Section 4 for the timing of assessments. 
13.3. 
Pharmacokinetic Assessments 
Not applicable. 
13.4. 
Pharmacodynamic Assessments 
Not applicable. 
13.5. 
Additional Assessments 
In addition to the efficacy assessments above, the following tests will be performed. 
13.5.1. 
Hemophilia Joint Health Score 
Joint assessment will be conducted at Visit 1 using a modified Hemophilia Joint Health Score 
(HJHS) for adult subjects.  This assessment is based on the scoring system used in a joint scoring 
reliability study in boys with hemophilia [Hilliard 2006].  It has been used as a tool to evaluate 
musculoskeletal outcomes in a cohort of 20 boys, aged 4 to 17 years [Saulyte Trakeymieine 
2010].  Modifications were included to adapt the HJHS scoring system to an adult hemophilia 
population and according to comments in a recent validation study by the International 
Hemophilia Prophylaxis Study Group [Feldman 2011]. 
Pediatric subjects will continue to use the HJHS, Version 2.1, and a joint assessment will be 
conducted at Visit 1.  Version 2.1 was published as an appendix to a validation study of Version 
1.0 [Feldman 2011]. 
Subjects from other parent studies will continue to use the joint health assessment instrument 
used in parent study. 
Joint health assessments will only be performed if they were conducted during the parent study. 
13.5.2. 
Patient-Reported and Health Outcomes 
Only patient-reported outcomes that were completed during the parent study should be 
completed during the current study.  If a subject goes outside of the age range for a 
questionnaire, he should no longer complete it.  The following patient-reported outcome 
assessments will be performed, if applicable, for all subjects every 6 months, where linguistic 
validations exist in which the subject and/or parent/guardian is fluent.  For pediatric subjects, 

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caregivers will perform these assessments, as appropriate.  The Investigator will administer the 
following age-appropriate questionnaires at the appropriate visits. 
 Haem-A-QoL [von Mackensen & Gringeri 2009] 
 Haemo-QoL [von Mackensen 2004] 
 Hemo-Sat-Patient Satisfaction Scale for parent/guardian, Version 15 [MAPI Research 
Institute 2009] 
 CHO-KLAT [CHO-KLAT 2009] 
o Children Version 2.0 (for children previously enrolled in study 9HB02PED 
who are less than 18 years of age). 
o Proxy, Version 2.0p (for parent/guardian of children who were previously 
enrolled in study 9HB02PED and who are less than 18 years of age) 
 EQ-5D-Y [EQ-5D-Y 2011] 
 EQ-5D-3L [EuroQol 1990] 
Other patient-reported health outcomes related to hemophilia that are assessed include:  
 Number of hospitalizations, excluding pre-planned hospitalizations, elective surgery 
documented at Visit 1, and emergent surgery 
 Number of emergency room visits  
 Number of physician visits excluding study visits 
 Number of hospitalization days  
 Number of days off work, school/daycare, or preschool  
 Number of days off work for a parent/guardian 
13.5.3. 
Optional Laboratory Assessment 
For subjects who give their consent (or whose parent/guardian gives consent for pediatric 
subjects), a sample of blood will be collected during the study to conduct an analysis of genetic 
risk factors in the hemophilia B patient population.  This exploratory laboratory assessment 
consists of DNA testing with full genome sequence. 

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13.5.4. 
Archive Plasma Samples 
Samples for FIX inhibitor testing will be collected for each subject, at each visit, for back-up and 
archiving.  Samples will be archived for testing (if required) for immunology, further coagulation 
assays, or for clarification of any clinical or laboratory AE. 

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14. 
SAFETY ASSESSMENTS 
Subjects that enroll into this study will be assessed only for those parameters that had been 
previously assessed in the parent study. 
14.1. 
Clinical Safety Assessments 
The following clinical assessments will be performed to assess the safety profile of rFIXFc: 
 Physical examination  
 Vital signs (blood pressure, pulse, respiratory rate, and temperature [°C]) 
 Medical and surgical history (from previous study and updated) 
 Height 
 Weight 
 Concomitant therapy and procedures  
 AEs and SAEs 
Refer to Section 4 for the timing of assessments. 
14.2. 
Laboratory Safety Assessments 
The following laboratory tests will be performed by the central laboratory to assess the safety 
profile of rFIXFc: 
 Hematology:  White blood cell count (WBC), differential, platelet count, hemoglobin, 
hematocrit 
 Blood chemistry:  sodium, potassium, chloride, glucose, total protein, total bilirubin, 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), blood urea nitrogen (BUN), and serum creatinine. 
 Nijmegen-modified Bethesda assay for development of inhibitors 
 Refer to Section 4 for the timing of assessments. 

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15. 
SAFETY DEFINITIONS, MONITORING, AND REPORTING 
Throughout the course of the study, every effort must be made to remain alert to possible AEs.  
If an AE occurs, the first concern should be for the safety of the subject.  If necessary, 
appropriate medical intervention should be provided. 
At the signing of the informed consent form (ICF), each subject must be given the names and 
telephone numbers of study site staff for reporting AEs and medical emergencies. 
15.1. 
Definitions 
15.1.1. 
Serious Pretreatment Event 
The term serious pretreatment event  is not applicable in this extension study as all AEs 
occurring up to the time of subject consent in this study 
previous study records. 
15.1.2. 
Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject who has 
been administered a pharmaceutical product and who does not necessarily have a causal 
relationship with this treatment.  An AE can, therefore, be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not it is related to the medicinal 
(investigational) product. 
Bleeds in this patient population are generally not considered AEs.  Bleeding episodes that meet 
any criteri
 (Section 15.1.3) should be reported as SAEs.  All bleeding episodes will 
be captured in the eDiary maintained by the subject throughout the study period. 
15.1.3. 
Serious Adverse Event 
An SAE is any untoward medical occurrence that, at any dose: 
 results in death 
 in the view of the Investigator, places the subject at immediate risk of death (a 
life-threatening event); however, this does not include an event that, had it occurred 
in a more severe form, might have caused death 
 requires inpatient hospitalization or prolongation of existing hospitalization 
 results in persistent or significant disability/incapacity 
 results in a congenital anomaly/birth defect 

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All major surgeries will be reported as SAEs.  An SAE may also be any other medically 
important event that, in the opinion of the Investigator, may jeopardize the subject or may 
require intervention to prevent one of the other outcomes listed in the definition above.  
(Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or convulsions occurring at home that do not require an inpatient 
hospitalization). 
15.2. 
Monitoring and Recording Events 
15.2.1. 
Serious Pretreatment Events 
A serious pretreatment event is not applicable in this extension study as all AEs occurring up to 
. 
15.2.2. 
Adverse Events 
Any AE experienced by the subject during participation in this extension study is to be recorded 
on the eCRF, regardless of the severity of the event or its relationship to the study treatment. 
In addition, any known, untoward event that occurs subsequent to the AE reporting period that 
the Investigator assesses as related to the investigational medication/product should also be 
reported as an AE. 
15.2.3. 
Serious Adverse Events 
Any SAE experienced by the subject between the day of signing the ICF and the last study 
follow-up visit/telephone call is to be recorded on an SAE Form and eCRF, regardless of the 
severity of the event or its relationship to study treatment.  Serious adverse events that occur up 
to 21 days a
 Form and 
eCRF.  Serious adverse events must be reported to Quintiles and to designated personnel, as 
detailed in the study file. 
Any SAE that is ongoing when the subject completes the study or discontinues from the study 
will be followed by the Investigator until the event has resolved, stabilized, or returned to 
baseline status. 
Subjects will be followed for all SAEs until the last study follow-up visit/telephone call.  
Thereafter, the event should only be recorded if the Investigator considers it related to study 
treatment. 
In this study, the following events are considered medically important and must be reported as 
SAEs: 
 A subject develops an inhibitor, as defined in Section 7.1.2. 

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A Grade 2 or greater allergic drug reaction in association with administration of 
rFIXFc, as defined below by the Recommendations for Grading of Acute and Sub-
Acute Toxic Effects on the WHO scale [WHO handbook 1979]: 
o Grade 2 
Bronchospasm related to rFIXFc; no parenteral therapy needed 
o Grade 3 
Bronchospasm related to rFIXFc; parenteral therapy required 
o Grade 4 
Anaphylaxis related to rFIXFc 
 A subject develops a vascular thrombotic event in association with the administration 
of rFIXFc, with the exception of IV injection site thrombophlebitis. 
All major surgeries will be reported as SAEs. 
Subjects will be informed of early symptoms and signs of thrombotic phenomena, including pain 
and/or tenderness along a vein, swelling of an arm or leg without pain or tenderness, redness 
along a vein, low fever without any known reason (such as a cold or flu), sudden shortness of 
breath or difficulty breathing or coughing, sudden chest pain, sudden severe headache or changes 
in vision, and numbness or tingling in arms or legs.  If such an event occurs while the subject is 
at home, the subject should be instructed to seek immediate medical care. 
15.2.4. 
All Events 
All events must be assessed to determine the following: 
 If the event meets the criteria for an SAE as defined in Section 15.1.3 
 The relationship of the event to study treatment as defined in Section 15.3.1 
 The severity of the event as defined in Section 15.3.2 
15.2.5. 
Immediate Reporting of Serious Adverse Events 
In order to adhere to all applicable laws and regulations for reporting an SAE, the study site must 
formally notify Quintiles Pharmacovigilance within 24 hours of the study site staff becoming 
aware of the SAE.  
information and procedures are used and followed appropriately. 

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Reporting Information for SAEs 
Any Serious Event that occurs between the time the subject has signed the ICF and up to 21days 
after the final dose of study treatment must be reported to Quintiles Pharmacovigilance within 24 
hours of the study site staff becoming aware of the event. 
A report must be submitted to Quintiles Pharmacovigilance regardless of the following: 
 whether or not the subject has undergone study-related procedures 
 whether or not the subject has received study treatment 
 the severity of the event 
 the relationship of the event to study treatment 
To report initial or follow-up information on a Serious Event, fax a completed SAE form to the 
following:   
Fax:  Please fax to Quintiles Pharmacovigilance at the country-specific fax number 
provided in the Study Manual. 
 
15.2.5.1. Deaths 
Death is an outcome of an event.  The event that resulted in death should be recorded and 
reported on the appropriate eCRF.  All causes of death must be reported as SAEs.  The 
Investigator should make every effort to obtain and send death certificates and autopsy reports to 
Quintiles Pharmacovigilance. 
15.3. 
Safety Classifications 
15.3.1. 
Relationship of Events to Study Treatment 
The following definitions should be considered when evaluating the relationship of AEs and 
SAEs to the study treatment:   

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Relationship of Event to Study Treatment 
Not related 
investigational 
drug if there is not a possibility that the event has been caused by the product under 
investigation.  Factors pointing toward this assessment include, but are not limited to:  
the lack of reasonable temporal relationship between administration of the drug and 
the event, the presence of a biologically implausible relationship between the product 
and the adverse event (e.g., the event occurred before administration of drug), or the 
presence of a more likely alternative explanation for the adverse event. 
Related 
there is a possibility that the event may have been caused by the product under 
investigation.  Factors that point toward this assessment include, but are not limited to:  
a positive re-challenge, a reasonable temporal sequence between administration of the 
drug and the event, a known response pattern of the suspected drug, improvement 
following discontinuation or dose reduction, a biologically plausible relationship 
between the drug and the adverse event, or a lack of an alternative explanation for the 
adverse event. 
 
15.3.2. 
Severity of Events 
The following definitions should be considered when evaluating the severity of AEs and SAEs: 
 
Severity of Event 
Mild 
The symptom(s) is barely noticeable to the subject or does not make the subject 
uncomfortable; does not influence performance or functioning; prescription drug is 
not ordinarily needed for relief of the symptom(s) but may be given because of the 
personality of subject. 
Moderate 
The symptom(s) of a sufficient severity to make the subject uncomfortable; 
performance of daily activity is influenced; the subject is able to continue in study; 
treatment for the symptom(s) may be needed. 
Severe 
The symptom(s) causes severe discomfort; symptom(s) cause incapacitation or 
significant impact on the 
treatment with study treatment; treatment for the symptom(s) may be given and/or 
subject hospitalized. 
 
15.3.3. 
Expectedness of Events 
Expectedness of all AEs will be determined according to the 
 for rFIXFc. 

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15.4.
Procedures for Handling Special Situations
15.4.1. 
Overdose 
An overdose is any single dose of study treatment given to a subject or taken by a subject that 
exceeds the maximum dose described in the protocol, 150 IU/kg.  All overdoses should be 
recorded on an Overdose Form and faxed to Quintiles Pharmacovigilance within 24 hours.  An 
overdose should be reported even if it does not result in an AE.  Overdoses do not need to be 
recorded in the eCRF; dosing information is recorded in the eCRF. 
15.4.2. 
Medical Emergency 
In a medical emergency requiring immediate attention, study site staff will apply appropriate 
medical intervention, according to current standards of care.  The Investigator should contact the 
Sponsor Medical Director for this study, Baisong Mei at +1-857-928-3348 (mobile) or Geoffrey 
Allen, MD at +1-781-558-0857 (mobile). 
15.4.3. 
Pregnancy 
The population under study is male; therefore pregnancies will not be tracked. 
Congenital abnormalities/birth defects in the offspring of male subjects should be reported when 
study drug-exposed conception occurs. 
15.4.4. 
Regulatory Reporting 
Suspected Unexpected Serious Adverse Reactions (SUSARs) are SAEs that are unexpected and 
judged by the Investigator or the Sponsor to be related to the study treatment administered. 
The Sponsor/designee will report SUSARs to the appropriate regulatory authorities and 
Investigators as required, according to local law. 
15.5. 
Investigator Responsibilities 
 
 Monitor and record all AEs, including SAEs, regardless of the severity or relationship 
to study treatment. 
 Determine the seriousness, relationship, and severity of each event. 
 Determine the onset and resolution dates of each event. 
 Report congenital abnormalities/birth defects in the offspring of male subjects when 
study drug-exposed conception occurs. 

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Complete an SAE form for each serious event and fax it to Quintiles
Pharmacovigilance within 24 hours of the study site staff becoming aware of the 
event. 
 Pursue SAE follow-up information actively and persistently.  Follow-up information 
must be reported to Quintiles Pharmacovigilance within 24 hours of the study site 
staff becoming aware of new information. 
 
medical records. 
 Report SAEs to local ethics committees, as required by local law. 
15.6. 
Biogen Idec Responsibilities 
responsibilities include the following: 
 Before study site activation and subject enrollment, the Clinical Monitor or Sponsor 
designee is responsible for reviewing with study site staff the definitions of AE and 
SAE, as well as the instructions for monitoring, recording, and reporting AEs and 
SAEs. 
 Biogen Idec is to notify all appropriate regulatory authorities, central ethics 
committees, and Investigators of SAEs, as required by local law, within required time 
frames. 

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16. 
STATISTICAL METHODS AND DETERMINATION OF 
SAMPLE SIZE 
In general, subjects who enroll into study 9HB01EXT from any rFIXFc parent study will have 
their parent study data integrated with their data from 9HB01EXT.  A parent study is defined as 
a study where subjects may be enrolled into 9HB01EXT after study completion or at a time 
specified in the protocol. .   
All statistical analyses will be descriptive in nature.  No formal comparison is planned and no 
hypothesis will be formally tested.  Continuous variables will be summarized and presented by 
number, mean, median, standard deviation, minimum and maximum, and, where appropriate, 
with the 25th and 75th percentiles.  Categorical variables will be summarized by the number and 
percentage in each category.     
16.1. 
Description of Objectives 
16.1.1. 
Primary Objective 
See Section 6.1.1 for 
 
16.1.2. 
Secondary Objective 
See Section 6.1.2 for 
 
16.2. 
Description of Endpoints 
16.2.1. 
Primary Endpoint 
See Section 6.2.1 for the study s primary endpoint. 
16.2.2. 
Secondary Endpoint 
See Sections 6.2.2 and 6.2.3 
. 
16.3. 
Demography and Baseline Disease Characteristics 
The analysis of demography and baseline disease characteristics will be based on the Safety 
Analysis Set.  The Safety Analysis Set includes all subjects who have received at least one dose 
of rFIXFc, as described in Section 16.6.1 .   
Demographic and baseline disease characteristics will be summarized categorically and/or 
with descriptive statistics, as appropriate, using the data at the entry into the parent studies.  
Demographic data to be tabulated includes age, race, hemophilia history, genotype, and other 
disease-specific measures.   

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Baseline disease characteristics, based on general medical and surgical, hemophilia, and bleeding 
histories, will be summarized by 9HB01EXT treatment regimen and overall, as follows.  General 
medical and surgical history will be summarized by the number and percentage of subjects with 
a medical history in each of the major body system classifications.  Hemophilia history data to be 
tabulated will include genotype and other disease- and treatment-specific measures. 
16.4. 
Efficacy 
16.4.1. 
Analysis Population 
All subjects who consent to participate in 9HB01EXT will be included in the All-enrolled 
Analysis Set. 
Subjects who receive at least 1 dose of rFIXFc will be included in the Full Analysis Set (FAS).  
Efficacy analyses will be based on the FAS. 
16.4.2. 
General Methods of Analysis 
All efficacy endpoints are secondary.  No imputation will be applied to any missing efficacy 
data.  The periods in which data will be used for efficacy and surgical rehabilitation analyses will 
be defined in the statistical analysis plan.  Data on bleeding and rFIXFc consumption will be 
based on the efficacy period; surgical evaluations will be based on the surgical/rehabilitation 
period. 
Analysis of efficacy endpoints that are visit-based will include data from all study visits, whether 
or not they occurred during the efficacy period.  However, if a visit is coincidental with a 
surgical/rehabilitation period for a major surgery, it will be excluded from the analysis. 
16.4.3. 
Endpoint Analysis 
16.4.3.1. Annualized Bleeding Episodes and Annualized rFIXFc Consumption  
Bleeding episodes will be annualized for each subject first, and then summarized and tabulated 
by treatment arm, treatment regimen, or age cohort, as appropriate, for the parent studies and the 
treatment regimen in Study 9HB01EXT.  These analyses will also be performed for each type of 
bleed (spontaneous, and traumatic).   Summaries of these data will be based on the FAS. 
16.4.3.2. Other Efficacy Endpoints  
The response to treatment for bleeding will be summarized by the number and percentage of 
bleeding episodes for each response (excellent, good, moderate, none).  These data will be 
summarized overall during each study based on the FAS.   

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16.4.3.3. Surgery Endpoints 
Analysis of surgery endpoints will be performed for subjects who had surgeries during the study, 
either emergently or electively.  Summary statistics of major surgery endpoints will be provided 
for the surgical/rehabilitation period. 
16.4.4. 
Additional/Exploratory Analysis 
The number of injections and the dose per injection required to resolve bleeding will be 
summarized on both a per-bleeding-episode and a per-subject basis, where the per-subject basis 
will be determined as the overall average across all bleeding episodes for a given subject.  These 
data will be summarized overall and for subgroups of interest during each study based on 
the FAS.  Other efficacy analyses can be conducted for exploratory purposes.   
16.5. 
Patient-Reported and Health Outcomes 
16.5.1. 
Analysis Population 
The FAS will be used for the analysis of patient-reported and health outcomes. 
16.5.2. 
Methods of Analysis 
16.5.2.1. Patient-Reported Outcomes 
Questionnaires for patient-reported outcomes are described in Section 13.5.2. 
Endpoints for patient-reported outcomes (Haem-A-QoL, Haemo-QoL, Hemo-Sat-P, 
CHO--KLAT Children, CHO--KLAT Proxy, EQ-5D-Y, and EQ-5D-3L) will be analyzed in a 
separate report.  These endpoints will be analyzed by summarizing actual values and change 
from baseline, as appropriate.   
16.5.2.2. Health Outcomes 
Summary statistics of health outcome endpoints will be tabulated at each data collection 
timepoint. 
16.6. 
Safety 
16.6.1. 
Analysis Population 
Subjects who receive at least one dose of rFIXFc will be included in the Safety Analysis Set. 
16.6.2. 
Methods of Analysis 
For the analysis of safety, data in 9HB01EXT will be integrated with the parent study data, 
unless specified otherwise.  The incidence of AEs will be tabulated overall, by severity, and by 
relationship to treatment.  In addition, the incidence of AEs will be presented by exposure day 
(ED) intervals.  An ED is a 24-hour period, in which one or more rFIXFc injections are given.  

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Subject listings will be provided for all AEs, SAEs, AEs resulting in discontinuation of the study 
treatment or withdrawal from the study, and death.  Findings for clinical lab values will be 
summarized by descriptive statistics.  Listings of vital signs and abnormal laboratory test results 
will be provided.     
The total number of EDs of rFIXFc will be summarized by treatment regimen and overall for 
9HB01EXT, and overall using combined data from the parent studies and 9HB01EXT. 
16.7. 
Inhibitor Formation Data 
16.7.1. 
Analysis Population 
The Safety Population (as defined in Section 16.6.1) will be the basis for analyses of inhibitor 
formation. 
16.7.2. 
Methods of Analysis 
The proportion of subjects with an inhibitor during rFIXFc administration will be provided with 
the exact (Clopper-Pearson) 2-sided, 95% confidence interval.  Any subject with an inhibitor (as 
defined in section 7.1.2) following the initial rFIXFc administration, will be counted in the 
numerator; however, only subjects who have completed at least 50 EDs, and 100 EDs from their 
initial rFIXFc administration, will be included in the denominator.  Unless all subjects complete 
at least 50 EDs, the proportion of subjects with an inhibitor will also be calculated using all 
subjects, regardless of the amount of exposure to rFIXFc, in the denominator. 
16.8. 
Optional Laboratory Assessments 
DNA testing with full genome sequence data may be performed to evaluate genetic risk factors 
in the hemophilia B patient population.  The analysis, however, will be in a separate report and 
will not be included as part of any Clinical Study Report (CSR) or interim CSR of 9HB01EXT. 
16.9. 
Interim Analyses 
Interim analyses will be conducted during the study, as needed.  Analyses will be descriptive in 
nature.  No formal comparisons are planned and no hypotheses will be formally tested. 
Due to the open-label nature of this study, personnel involved in conducting the interim analyses 
will have access to treatment assignments. 
16.10. 
Sample Size Considerations 
This is an extension study.  Sample size is based on the planned sample sizes of Studies 
998HB102 (N=100), 9HB02PED (N=20), and may be increased based upon subject participation 
in other rFIXFc parent studies. 

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17. 
ETHICAL REQUIREMENTS 
The Sponsor and the Investigator must comply with all instructions, regulations, and agreements 
in this protocol and applicable International Conference on Harmonisation (ICH) and Good 
Clinical Practice (GCP) guidelines and conduct the study according to local regulations. 
17.1. 
Declaration of Helsinki 
The Investigator and Sponsor must adhere to the principles set forth by the Declaration of 
Helsinki, dated October 2008. 
17.2. 
Ethics Committee 
The Investigator must obtain ethics committee approval of the protocol, ICF, and other required 
study documents prior to starting the study. 
If the Investigator makes any changes to the ICF, the Sponsor must approve the changes before 
the ICF is submitted to the ethics committee.  A copy of the approved ICF must be provided to 
the Sponsor.  After approval, the ICF must not be altered without the agreement of the relevant 
ethics committee and the Sponsor. 
It is the responsibility of the Principal Investigator(s) to ensure that all aspects of institutional 
review are conducted in accordance with current governmental regulations. 
The Sponsor must receive a letter documenting ethics committee approval, which specifically 
identifies the protocol, protocol number, and ICF, prior to the initiation of the study.  Protocol 
amendments will be subject to the same requirements as the original protocol. 
A progress report must be submitted to the ethics committee at required intervals and not less 
than annually. 
At the completion or termination of the study, the investigational site must submit a close-out 
letter to the ethics committee and the Sponsor. 
17.3. 
Subject Information and Consent 
Prior to performing any study-related activities under this protocol, including screening tests and 
assessments, written informed consent with the approved ICF must be obtained from the subject 
 as applicable, in accordance with local practice and 
regulations.  Written informed consent must be obtained from all subjects participating in a 
clinical study conducted by the Sponsor. 
The background of the proposed study, the procedures, the benefits and risks of the study, and 
that study participation is voluntary for the subject must be explained to the subject.  The subject 
must be given sufficient time to consider whether to participate in the study. 

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A copy of the ICF, signed and dated by the subject, must be given to the subject.  Confirmation 
any testing under this protocol, including screening tests and assessments. 
Each consent form should contain an authorization allowing the Principal Investigator(s) and the 
Sponsor to use and disclose PHI (i.e., subject-identifiable health information) in compliance with 
local law. 
The signed consent form will be retained with the study records. 
For subjects who are under 18 years of age (or legally a minor per local regulations), or who are 
otherwise unable to provide written informed consent, a parental/guardian consent will be 
obtained, the contents of which will be identical to that of the standard adult consent.  Written 
subject assent will also be obtained from those subjects who are able to read and understand the 
assent form, a brief summary of the study process, benefits, and risks. 
17.4. 
Subject Data Protection 
Prior to any testing under this protocol, including screening tests and assessments, candidates 
must also provide all authorizations required by local law (e.g., PHI authorization in North 
America). 
The subject will not be identified by name in the eCRF or in any study report, and these reports 
will be used for research purposes only.  The Sponsor, its partner(s) and designee(s), ethics 
committees, and various government health agencies may inspect the records of this study.  
 
17.5. 
Compensation for Injury 
The Sponsor maintains appropriate insurance coverage for clinical trials and will follow 
applicable local compensation laws. 
17.6. 
Conflict of Interest 
The Investigators should address any potential conflicts of interest (e.g., financial interest in the 
Sponsor) with the subject before the subject makes a decision to participate in the study. 
17.7. 
Registration of Study and Disclosure of Study Results 
The Sponsor will register the study and post study results regardless of outcome on a publicly 
accessible website in accordance with the applicable laws and regulations. 

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18. 
ADMINISTRATIVE PROCEDURES 
18.1. 
Study Site Initiation 
The Investigator must not screen any subjects prior to completion of a study initiation visit, 
conducted by the Sponsor or designee.  This initiation visit will include a detailed review of the 
protocol and study procedures. 
18.2. 
Study Supplies 
The Sponsor will supply the rFIXFc while subjects participate in this study (see Section 12).  
Since study subjects will be required to maintain accurate records of each dose of rFIXFc 
administered during the study, the Sponsor will provide personal eDiaries to the study sites for 
subjects to use to record study information. 
18.3. 
Quality Assurance 
During and/or after completion of the study, quality assurance officers named by the Sponsor or 
the regulatory authorities may wish to perform on-site audits.  The Investigator will be expected 
to cooperate with any audit and to provide assistance and documentation (including source data) 
as requested. 
18.4. 
Monitoring of the Study 
The Principal Investigator(s) must permit study-related monitoring by providing direct access to 
source data and to the su
 
The Clinical Monitor(s) will visit the Investigator(s) at regular intervals during the course of the 
study and after the study has completed, as appropriate. 
During these visits, eCRFs and supporting documentation related to the study will be reviewed 
and any discrepancies or omissions will be resolved. 
Section 19.1.3 will be used as source data. 
The monitoring visits must be conducted according to the applicable ICH and GCP guidelines to 
ensure protocol adherence, quality of data, study treatment accountability, compliance with 
regulatory requirements, and continued adequacy of the investigational site and its facilities. 
18.5. 
Study Funding 
The Sponsor will pay the clinic or institution where the study is conducted for the costs of 
running the study.  All financial details are provided in the separate contract(s) between the 
Institution/Investigator and Sponsor. 

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18.6.
Publications
Details are included in the clinical trial agreement for this study. 
 

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19. 
FURTHER REQUIREMENTS AND GENERAL INFORMATION 
19.1. 
External Contract Organizations 
19.1.1. 
Contract Research Organization  
A contract research organization (CRO) will be responsible for administrative aspects of the 
study including, but not limited to, study initiation, monitoring, and management of SAE reports 
and data management.  Before subjects are screened at each study site, the CRO will review 
study responsibilities with the Investigators and other study site staff, as appropriate. 
19.1.2. 
Interactive Voice/Web Response System 
Interactive Voice and Web Response System (IXRS) will be used in this study.  Before subjects 
are screened or enrolled, the IXRS vendor will provide each study site with appropriate training 
and a user manual. 
19.1.3. 
Electronic Data Capture 
Subject information will be captured and managed by study sites on eCRFs by a web-based 
electronic data capture (EDC) tool (eDiary) developed and supported by the EDC vendor and 
configured by the Sponsor. 
Data entered by subjects using the eDiary will be downloaded to the database. 
19.1.4. 
Central Laboratories for Laboratory Assessments 
Central laboratories have been selected by the Sponsor to analyze all hematology, blood 
chemistry, inhibitor, and antibody samples collected for this study.  Specifics regarding the 
requirements for laboratory specimen collection, handling, and analysis are provided in the study 
Laboratory Manuals, which are part of the Study Manual. 
19.2. 
Changes to Final Study Protocol 
All protocol amendments must be submitted to the ethics committee and Regulatory Authorities 
if required by local law.  Protocol modifications that affect subject safety, the scope of the 
investigation, or the scientific quality of the study must be approved by the ethics committee 
before implementation of such modifications to the conduct of the study.  If required by local 
law, such modifications must also be approved by the appropriate regulatory agency prior to 
implementation. 
However, the Sponsor may, at any time, amend this protocol to eliminate an apparent immediate 
hazard to a subject.  In this case, the appropriate regulatory authorities will be notified 
subsequent to the modification. 

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In the event of a protocol modification, the subject consent form may require similar 
modifications (see Sections 17.2 and 17.3). 
19.3. 
Ethics Committee Notification of Study Completion or Termination 
Where required, the Health Authorities and ethics committees must be notified of completion or 
termination of this study, and sent a copy of the study synopsis in accordance with necessary 
timelines. 
19.4. 
Retention of Study Data 
The minimum retention time for study records will meet the strictest standard applicable to that 
site, as dictated by any institutional requirements or local laws or regulations.  Prior to 
proceeding with destruction of records, the Investigator must notify Biogen Idec in writing and 
receive written authorization from Biogen Idec to destroy study records.  In addition, the 
Investigator must notify Biogen Idec of any changes in the archival arrangements including, but 
not limited to, archival at an off-site facility or transfer of ownership if the Investigator leaves the 
site. 
19.5. 
Study Report Signatory 
The Sponsor will designate one of the participating Study Investigators as a signatory for the 
study report.  This determination will be made by several factors, including, but not limited to, 
the Investigator s experience and reputation in the studied indication, the Investigator s 
contribution to the study in terms of design, management, and/or subject enrollment, or by other 
factors determined to be relevant by the Sponsor. 
The Sponsor will follow all applicable local regulations pertaining to study report signatories. 

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20. 
REFERENCES 
Canadian Hemophilia Outcomes-
 
Canadian Hemophilia Outcomes-
-Proxy, Version 2, 2009. 
Colvin BT, Astermark J, Fischer K, et al.European principles of haemophilia 
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Committee for Proprietary Medicinal Products (CPMP).Note for Guidance on the Clinical 
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EQ-5D-Y, Version 4.0, 2011. 
European Medicines Agency. Guideline on clinical investigation of recombinant and human 
plasma-derived factor IX products. EMA/CHMP/BPWP/144552/2009. July 21, 2011. 
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The EuroQol Group.EuroQol-a new facility for the measurement of health-related quality of 
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Feldman BM et al.Validation of a new pediatric joint scoring system from the International 
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Giangrande P.Haemophilia B: Christmas disease.  Expert Opin.  Pharmacother.  2005; 
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Gringer A, Mantovani L, and Mackensen S.Quality of life assessment in clinical practice in 
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Lambert T, Recht M, Valentino, et al.Reformulated BeneFix®: efficacy and safety in 
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Peters RT, Low SC, Kamphaus GD, et al.Prolonged activity of factor IX as a monomeric Fc 
fusion protein.Blood 2010;115(10):2057-2064. 
Roberts HR, Eberst ME.Current management of hemophilia B.Hematol Oncol Clin North 
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Roth D, Kessler CM, Pasi KJ, et al.Human recombinant factor IX:  safety and efficacy 
studies in hemophilia B patients previously treated with plasma-derived factor IX 
concentrates.Blood 2001; 98:3600-3606. 
Saulyte Trakymiene S, Ingerslev J, Rageliene L.Utility of the Haemophilia Joint Health 
Score in the study of episodically treated boys with severe haemophilia A and B in 
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Skinner MW. WFH: Closing the global gap--achieving optimal care. Haemophilia. 2012;18 
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Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of 
hemophilia. Haemophilia. 2013;19(1):e1-e47. 
Von Mackensen S, Bullinger M, Haemo-QoL Group.Development and testing of an 
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Von Mackensen S, Gringeri A.Quality of Life in Hemophilia.In: Preedy VR & Watson RR.  
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White G, Shapiro A, Ragni M, Garzone P, Goodfellow J, Tubridy K, Courter S.Clinical 
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World Health Organization handbook for reporting results of cancer treatment, 1979. 
 

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21. 
SIGNED AGREEMENT OF THE STUDY PROTOCOL 
I have read the foregoing 
An Open-Label, Multicenter, Evaluation of the Long-Term 
Safety and Efficacy of Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) in 
the Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects with 
Version 4, and agree to conduct the study according to the protocol and the 
applicable ICH guidelines and GCP regulations, and to inform all who assist me in the conduct 
of this study of their responsibilities and obligations. 
 
 
 
____________________________________________________ 
 
 
 
 
Date 
 
 
____________________________________________________ 
 
 
 
 
____________________________________________________ 
Study Site (Print) 

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APPENDIX A. rFIXFc DOSING GUIDELINE FOR TREATMENT OF 
BLEEDING EPISODES 
The following table provides guidance for dosing with rFIXFc for bleeding episodes.  Subjects 
should consult with the Investigator for an optimal rFIXFc level and dosing frequency.  Because 
of the long lasting effect of rFIXFc, it is recommended that the subject take the first follow-up 
dose no less than 48 hours after the initial dose.  However, if the subject experiences persistent 
pain or other signs of ongoing bleeding, the first follow-up dose may be administered before 
48 hours.  For major bleeding episodes the subjects will be instructed to administer treatment and 
contact the study staff as soon as possible. 
Table 3: 
Dosing Guidelines for rFIXFc Therapy in Hemophilia B 
Type of Hemorrhage 
Factor IX Level Required (%) 
Minor 
 
Epistaxis 
20-30 
Hemarthroses, uncomplicated 
20-30 
Superficial muscular 
20-30 
Superficial soft tissue 
20-30 
 
 
Moderate 
 
Epistaxis 
25-50 
Intramuscular with dissection 
25-50 
Soft tissue with dissection 
25-50 
Mucous membranes 
25-50 
Dental extractions 
25-50 
Hematuria 
25-50 
Hemarthroses, with limited motion 
40-80 
 
 
Major 
 
Epistaxis  
50-100 
Pharynx 
50-100 
Retropharynx 
50-100 
Retroperitoneum 
50-100 
Surgery 
50-100 
Central Nervous System (CNS) 
50-100 

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APPENDIX B. HEMOPHILIA JOINT HEALTH SCORE (HJHS) 
Appendix B1: 
Modified HJHS for Subjects Transferring from 
Study 998HB102 
This modified HJHS is based on the scoring system used in a joint scoring reliability study in 
boys with hemophilia [Hilliard 2006].The modifications were done to adapt the scoring system 
to an adult hemophilia population and according to comments in a recent validation study by the 
international hemophilia prophylaxis study group [Feldman 2011].This version is for use only 
with subjects who were previously enrolled in study 998HB102. 
Six joints (left ankle-LA, right ankle-RA, left elbow-LE, right elbow-RE, left knee-LK, right 
knee-RK) will be scored on a scale from 0 to 19 according to the following criteria:  swelling, 
duration, muscle atrophy, crepitus, flexion loss, extension loss, instability, joint pain, and 
strength.  Gait will be scored on a scale from 0 to 2 based on walking and climbing stairs.  The 
total score will be the sum of scores from all 6 joints plus the gait score (range from 0 to 116 
with 0 being normal and 116 being the most severe disease). 
SCORING DETAILS 
1. Joint scoring will be done separately for the 6 joints (LA, RA, LE, RE, LK, RK) 
according to these categories and scales (range is 0-19 for each joint and 0-114 for all six 
joints): 
Swelling 
0=none 
1=mild 
2=moderate 
3= severe 
Duration of swelling 
 
1= >6 months 
Muscle atrophy 
0=none 
1=mild 

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2=severe 
Crepitus on motion 
0=absent 
1=present 
Flexion loss (includes plantarflexion of ankles) 
0=none* 
1=mild* 
2=moderate* 
3=severe* 
Extension loss (includes dorsiflexion of ankles) 
0=none* 
1=mild* 
2=moderate* 
3=severe*  
*Use the following as guidance for scoring flexion loss and extension loss at knees and 
elbows:  
None:  approximately 0-5 degrees 
Mild:  approximately 5-10 degrees 
Moderate:  approximately 11-20 degrees 
Severe:  approximately >20 degrees 
Instability 
0=none 
1=significant pathologic joint laxity 
Joint pain 
0=no pain (either through range or at end range of motion) 

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1=present 
Strength 
0=normal (holds position against gravity and maximum resistance) 
1=minimal decrease (holds position against gravity and moderate resistance, but not 
maximum resistance) 
2=mild decrease (holds position against gravity or minimal resistance) 
3=moderate decrease (able to move joint if gravity eliminated) 
4=severe decrease (trace or no muscle contraction) 
2. Gait will be scored once (range is 0-2): 
0=No difficulty with walking or climbing up/down stairs 
1=No difficulty with walking, but difficulty with stairs 
2=Difficulty with walking and with stairs 
 
Total score = sum of all joint scores plus the gait score (range is 0-116) 
 
Appendix B2. 
HJHS Version 2.1 for All Other Subjects 
All subjects from rFIXFc parent studies that were evaluated with HJHS Version 2.1 (Hemophilia 
Joint Health Score, Version 2.1, 2011) will continue to use this score.   

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APPENDIX C. 
ASSESSMENT OF RESPONSE TO 
TREATMENT OF BLEEDING 
bleeding episode using the following 4-point scale (excellent, good, moderate, or none).  This 
assessment is to be made approximately 8 to 12 hours from the time the injection was given to 
treat the bleeding episode and prior to any additional doses of rFIXFc given for the same 
bleeding episode.  In this study, a bleed will be defined as follows:  a bleeding episode starts 
from the first sign of a bleed and ends no more than 72 hours after the last treatment for the 
bleed, within which any symptoms of bleeding at the same location, or injections less than or 
equal to 72 hours apart, are considered the same bleed.  Any injection to treat the bleed, taken 
more than 72 hours after the preceding one, will be considered the first injection to treat a new 
bleed at the same location.  Response could also be assessed by the Physician for those subjects 
who were treated in the clinic or in the hospital with rFIXFc for bleeds or post-surgery until 
discharge from the hospital. 
 Excellent:  Abrupt pain relief and/or improvement in signs of bleeding within 
approximately 8 hours after the initial injection 
 Good:  Definite pain relief and/or improvement in signs of bleeding within 
approximately 8 hours after an injection, but possibly requiring more than one 
injection after 24  48 hours for complete resolution 
 Moderate:  Probable or slight beneficial effect within 8 hours after the initial 
injection and requires more than one injection 
 None:  No improvement, or condition worsens within approximately 8 hours after the 
initial injection 
The following evaluations will determine the level of hemostasis achieved with rFIXFc treatment 
during surgery: 
 Number of injections and dose per injection required to maintain hemostasis during 
the surgical period 
 Estimated blood loss during surgery (intra-operative period) 
 Number and type of blood component transfusions required during surgery 
 

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APPENDIX D. 
SSESSMENT OF RESPONSE 
following 4-point scale: 
 Excellent:  
that usually observed. 
 Effective:  most bleeding episodes responded to the same number of injections and 
dose, but some required more injections or higher doses, or there was a minor 
increase in the rate of breakthrough. 
 Partially Effective:  bleeding episodes most often required more injections and/or 
higher doses than expected, or adequate breakthrough bleeding prevention during 
prophylaxis required more frequent injections and/or higher doses. 
 Ineffective:  routine failure to control hemostasis or hemostatic control requires 
additional agents. 
Investigators should consider the following, if available, when making the assessment: 
 Frequency of rFIXFc injections 
 Response to rFIXFc injection 
 Information reported in the eDiary by the subject 
 

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APPENDIX E. PHYSICIAN ASSESSMENT OF RESPONSE TO 
TREATMENT DURING SURGERY 
The Investigator/Surgeon who completed the minor or major surgical procedures will assess the 
-point clinical scale.  This includes 
observations made during surgery.  This assessment will be done within 24 hours after the 
surgery. 
Excellent:  intra-operative and post-operative blood loss similar to (or less than) the 
non-hemophilic patient. 
 No extra doses of rFIXFc needed AND 
 Blood component transfusions required are similar to person without hemophilia 
Good:  intra-operative and/or post-operative bleeding slightly increased over expectations for the 
non-hemophilic patient, but the difference is not clinically significant. 
 Intra-operative blood loss no more than expected for a person without hemophilia 
AND 
 No extra doses of rFIXFc needed AND 
 Blood component transfusions required are similar to person without hemophilia 
Fair:  intra-operative and/or post-operative blood loss is increased over expectation for the 
person without hemophilia and additional treatment is needed. 
 Intra-operative blood loss greater than expected for person without hemophilia OR 
 Extra dose of rFIXFc needed OR 
 Increased blood component transfusion requirement  
Poor/none:  significant intra-operative and/or post-operative bleeding that is substantially 
increased over expectations for the person without hemophilia, requires intervention, and is not 
explained by a surgical/medical issue other than hemophilia 
 Intra-operative blood loss greater than for the person without hemophilia OR 
 Unexpected hypotension or unexpected transfer to intensive care unit due to bleeding 
OR 
 Substantially increased blood component transfusion requirement 

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APPENDIX F. PATIENT REPORTED OUTCOMES 
The following quality of life questionnaires will be presented under separate cover: 
 Haem-A-QoL  
 Haemo-QoL  
 Hemo-Sat-P Patient Satisfaction Scale for parents/guardians, Version 15 
 CHO-KLAT 
o Children, Version 2.0 (for children previously enrolled in study 9HB02PED who 
are less than 18 years of age). 
o Proxy, Version 2.0p (for parents/guardians of children who were previously 
enrolled in study 9HB02PED and who are less than 18 years of age) 
 EQ-5D Y  
 EQ-5D 3L