B-YOND: Long-Term Safety and Efficacy of rFIXFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia B

• Sponsor: Bioverativ Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01425723
• Collaborator: (none)
• Enrollment: 120
• Locations: 49
• Arms: 2
• Actual Duration (Months): 69.8
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the long-term safety of rFIXFc in participants with hemophilia B.

The secondary objective of this study is to evaluate the efficacy of rFIXFc in the prevention and treatment of bleeding episodes.

Condition or Disease	Intervention/Treatment	Phase
Severe Hemophilia B	Biological: rFIXFc	Phase 3

Detailed Description

Participants will follow either a prophylaxis or on-demand regimen. The starting dose in this study will be determined by the clinical profile of the patient in the preceding studies, B-LONG 998HB102 (NCT01027364) and Kids B-LONG study 9HB02PED (NCT01440946)

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Dec 8, 2011
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: On-Demand The individual dose of rFIXFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor IX peak (recovery) levels.	Biological: rFIXFc; Administered as specified in the treatment arm.; Other Names: coagulation factor IX (recombinant) Fc fusion protein Alprolix BIIB029
Experimental: Prophylaxis Weekly prophylaxis, individualized prophylaxis or personalized prophylaxis available.	Biological: rFIXFc; Administered as specified in the treatment arm.; Other Names: coagulation factor IX (recombinant) Fc fusion protein Alprolix BIIB029

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Positive Inhibitor Development [Approximately 5 years]

   An inhibitor test result greater than or equal to (>=)0.6 Bethesda units per milliliter (BU/mL), confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Data was summarized by treatment regimen for participants from Study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

Secondary Outcome Measures

1. Annualized Bleeding Rate (ABR) [Approximately 5 years]

   ABR is annualized number of bleeding episodes per participant per year. Bleeding episodes were classified as spontaneous if participant records bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity and classified as traumatic if participant records bleeding event when there is known reason for bleed. ABR=(Number of bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. ABR was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

2. Annualized Spontaneous Joint Bleeding Episodes [Approximately 5 years]

   Bleeding episodes were classified as spontaneous if participant records a bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity. In addition, location of bleed (joint, internal, skin/mucosa or muscle) were also collected. Annualized spontaneous joint bleeding episodes=(Number of spontaneous joint bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Bleeding episodes were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

3. Total Number of Exposure Days (EDs) [Approximately 5 years]

   An exposure day is a 24-hour period in which one or more rFIXFc injections are given. The total number of days of exposure to rFIXFc were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

4. Annualized rFIXFc Consumption (International Units Per Kilogram [IU/kg]) [Approximately 5 years]

   Annualized consumption = (total international unit per kilogram [IU/kg] of study treatment received during the efficacy period / total number of days during the efficacy period) multiplied by 365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Annualized consumption was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

5. Physicians' Global Assessment of Participant's Response to rFIXFc Regimen Using a 4-Point Scale [Approximately 5 years]

   Participants were assessed for response to their rFIXFc regimen using following 4-point scale: 1=Excellent: bleeding episodes responded to less than or equal to (<=)usual number of injections or dose of rFIXFc or rate of breakthrough bleeding during prophylaxis was <= that usually observed; 2=Effective: most bleeding episodes responded to same number of injections and dose, but some required more injections or higher doses, or there was minor increase in rate of breakthrough; 3=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 and 4=Ineffective: routine failure to control hemostasis/hemostatic control require additional agents. Total number of scale responses =total count of scale responses for all participants; multiple responses per participant including those at scheduled and unscheduled visits are counted.

6. Participant's Assessment of Response (Excellent or Good Response) to rFIXFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale [Approximately 5 years]

   Using eDiary, participant received rating for treatment response to any bleeding episode (BE) using 4-point scale- 1=Excellent: Abrupt pain relief and/or improvement in signs of bleeding within approximately (approx.) 8 hours (h) after initial injection (inj.); 2=Good: Definite pain relief and/or improvement in signs of bleeding within approx. 8h after an injection, but possibly requiring more than 1 injection after 24-48h for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8h after initial injection and requires more than 1 injection and 4=None: No improvement, or condition worsens within approx. 8h after initial injection. This assessment was to be made approx. 8 to 12h from time the injection was given to treat BE and prior to any additional doses of rFIXFc given for same bleeding episode. Percentages are based on the number of bleeding episodes for which a response (excellent or good) was provided for the first injection during the efficacy period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Subjects who have completed studies 998HB102 (NCT01027364) or 9HB02PED (NCT01440946) or other studies with rFIXFc

• Ability to understand the purposes & risks of the study and provide signed and dated informed consent.

Key Exclusion Criteria:

• High-titer inhibitor (>/=5.00 BU/mL)

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85016
2	Research Site	Sacramento	California	United States	95817
3	Research Site	Aurora	Colorado	United States	80045
4	Research Site	Atlanta	Georgia	United States	30322
5	Research Site	Honolulu	Hawaii	United States	96826
6	Research Site	Indianapolis	Indiana	United States	46260
7	Research Site	New Orleans	Louisiana	United States	70112
8	Research Site	East Lansing	Michigan	United States	48823
9	Research Site	Pittsburgh	Pennsylvania	United States	15213
10	Research Site	Seattle	Washington	United States	98104
11	Research Site	Adelaide	South Australia	Australia	5000
12	Research site	Parkville	Victoria	Australia	3052
13	Research site	Murdoch	Western Australia	Australia	6150
14	Research Site	Perth	Western Australia	Australia	6008
15	Research Site	Bruxelles		Belgium	1200
16	Research Site	Leuven		Belgium	3000
17	Research Site	Campinas	Sao Paulo	Brazil	13083-878
18	Research Site	Toronto	Ontario	Canada	M5B 1W8
19	Research Site	Montreal	Quebec	Canada	H3T 1C5
20	Research Site	Beijing	Beijingshì	China	100005
21	Research Site	Guangzhou	Guangdongsheng	China	510515
22	Research Site	Shanghai	Shànghaishì	China	200025
23	Research Site	Tianjing	Tianjinshì	China	300020
24	Research Site	Marseille	Bouches-Du-Rhône	France	13385
25	Research Site	Bonn	North Rhine-westphalia	Germany	53127
26	Research Site	Hong Kong	New Territories	Hong Kong
27	Research site	Hong Kong		Hong Kong
28	Research Site	Bangalore	Karnataka	India	560034
29	Research Site	Pune	Maharashtra	India	411004
30	Research Site	Vellore	Tamil Nadu	India	632004
31	Research Site	Dublin		Ireland	D12 N512
32	Research Site	Florence		Italy	50134
33	Research Site	Milano		Italy	20122
34	Research Site	Nagoya-Shi	Aichi-Ken	Japan	466-8550
35	Research Site	Kitakyushu	Fukuoka-Ken	Japan	807-8555
36	Research Site	Kawasaki	Kanagawa-Ken	Japan	216-8511
37	Research Site	Kashihara-shi	Nara-Ken	Japan	634-8522
38	Research Site	Shinjuku-ku	Tokyo-To	Japan	160-0023
39	Research Site	Tokyo	Tokyo-To	Japan	167-8515
40	Research Site	Utrecht		Netherlands	3584 CX
41	Research Site	Lodz		Poland	93-510
42	Research Site	Johannesburg	Gauteng	South Africa	2193
43	Research Site	Cape Town	Western Cape	South Africa	7925
44	Research Site	Malmö		Sweden	20502
45	Research Site	Stockholm		Sweden	17176
46	Research Site	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
47	Research Site	London	Greater London	United Kingdom	E1 1BB
48	Research site	London	Greater London	United Kingdom	SE1 7EH
49	Research Site	Basingstoke	Hampshire	United Kingdom	RG24 9NA

Sponsors and Collaborators

• Bioverativ Therapeutics Inc.

Investigators

• Study Director: Medical Director, Bioverativ Therapeutics Inc.

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2013
• Statistical Analysis Plan - Sep 5, 2017

More Information

Publications

None provided.

• Responsible Party: Bioverativ Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT01425723
• Other Study ID Numbers: 9HB01EXT; 2011-003075-11
• First Posted: Aug 30, 2011
• Last Update Posted: Dec 19, 2020
• Last Verified: Nov 1, 2018

• Keywords provided by Bioverativ Therapeutics Inc.: B-LONG; B-YOND; B-LONG Extension; rFIXFc; Severe Hemophilia B
• Additional relevant MeSH terms: Hemophilia A; Hemophilia B

Study Results

Participant Flow

Pre-assignment Detail	Participants who completed either of the Phase 3 studies (Study 998HB102 [NCT01027364], Study 9HB02PED [NCT01440946]) were expected to be eligible to enroll in this study.

Arm/Group Title	rFIXFc (Participants From 9HB02PED)	rFIXFc (Participants From 998HB102)
Arm/Group Description	Participants received Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) intravenously (IV) according to their assigned treatment regimen as follows: Weekly prophylaxis (P): Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of greater than (>)5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg twice weekly versus 50 IU/kg once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 international units per kilogram (IU/kg) to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5 percent (%), if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Period Title: Overall Study
STARTED	27	93
Weekly Prophylaxis	23	51
Individualized Prophylaxis	5	31
Personalized Prophylaxis	2	17
Episodic	0	15
Surgery Subgroup	1	15
COMPLETED	23	75
NOT COMPLETED	4	18

Baseline Characteristics

Arm/Group Title	rFIXFc (Participants From 9HB02PED)	rFIXFc (Participants From 998HB102)	Total
Arm/Group Description	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of >5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg twice weekly versus 50 IU/kg once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.	Total of all reporting groups
Overall Participants	27	93	120
Age, Customized (Count of Participants)
<18 years	27 100%	8 8.6%	35 29.2%
Between 18 and 65 years	0 0%	85 91.4%	85 70.8%
> 65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	27 100%	93 100%	120 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	11 11.8%	11 9.2%
Not Hispanic or Latino	27 100%	78 83.9%	105 87.5%
Unknown or Not Reported	0 0%	4 4.3%	4 3.3%
Race/Ethnicity, Customized (Count of Participants)
White	19 70.4%	47 50.5%	66 55%
Black or African American	2 7.4%	9 9.7%	11 9.2%
Asian	5 18.5%	27 29%	32 26.7%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%
Other	1 3.7%	10 10.8%	11 9.2%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Positive Inhibitor Development
Description	An inhibitor test result greater than or equal to (>=)0.6 Bethesda units per milliliter (BU/mL), confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Data was summarized by treatment regimen for participants from Study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participants who received at least 1 dose of Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) in study 9HB01EXT.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old])	rFIXFc (9HB02PED [6 to <12 Years])	rFIXFc (Participants From 998HB102)
Arm/Group Description	Participants with less than (<) 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Annualized Bleeding Rate (ABR)
Description	ABR is annualized number of bleeding episodes per participant per year. Bleeding episodes were classified as spontaneous if participant records bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity and classified as traumatic if participant records bleeding event when there is known reason for bleed. ABR=(Number of bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. ABR was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants who received at least 1 dose of rFIXFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old Age Cohort])	rFIXFc (9HB02PED [6 to <12 Years Old Age Cohort])	rFIXFc (Participants From Study 998HB102)
Arm/Group Description	Participants with < 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Weekly Prophylaxis	1.04	1.14	2.26
Individualized Prophylaxis	3.69	1.85
Personalized Prophylaxis	0.54	3.13	2.91
Episodic	11.64

3. Secondary Outcome

Title	Annualized Spontaneous Joint Bleeding Episodes
Description	Bleeding episodes were classified as spontaneous if participant records a bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity. In addition, location of bleed (joint, internal, skin/mucosa or muscle) were also collected. Annualized spontaneous joint bleeding episodes=(Number of spontaneous joint bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Bleeding episodes were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of rFIXFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old Age Cohort])	rFIXFc (9HB02PED [6 to <12 Years Old Age Cohort])	rFIXFc (Participants From Study 998HB102)
Arm/Group Description	Participants with < 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Weekly Prophylaxis	0.00	0.00	0.38
Individualized Prophylaxis	0.00	0.38
Personalized Prophylaxis	0.00	0.00	0.30
Episodic	2.15

4. Secondary Outcome

Title	Total Number of Exposure Days (EDs)
Description	An exposure day is a 24-hour period in which one or more rFIXFc injections are given. The total number of days of exposure to rFIXFc were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participants who received at least 1 dose of rFIXFc in study 9HB01EXT. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old Age Cohort])	rFIXFc (9HB02PED [6 to <12 Years Old Age Cohort])	rFIXFc (Participants From Study 998HB102)
Arm/Group Description	Participants with < 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Weekly Prophylaxis	55.00	165.00	169.00
Individualized Prophylaxis	54.00	110.00
Personalized Prophylaxis	157.00	90.00	146.00
Episodic	52.00

5. Secondary Outcome

Title	Annualized rFIXFc Consumption (International Units Per Kilogram [IU/kg])
Description	Annualized consumption = (total international unit per kilogram [IU/kg] of study treatment received during the efficacy period / total number of days during the efficacy period) multiplied by 365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Annualized consumption was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of rFIXFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old Age Cohort])	rFIXFc (9HB02PED [6 to <12 Years Old Age Cohort])	rFIXFc (Participants From Study 998HB102)
Arm/Group Description	Participants with < 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Weekly Prophylaxis	3382.5	3212.0	2598.0
Individualized Prophylaxis	3700.7	2894.8
Personalized Prophylaxis	3331.7	8931.2	3671.2
Episodic	595.6

6. Secondary Outcome

Title	Physicians' Global Assessment of Participant's Response to rFIXFc Regimen Using a 4-Point Scale
Description	Participants were assessed for response to their rFIXFc regimen using following 4-point scale: 1=Excellent: bleeding episodes responded to less than or equal to (<=)usual number of injections or dose of rFIXFc or rate of breakthrough bleeding during prophylaxis was <= that usually observed; 2=Effective: most bleeding episodes responded to same number of injections and dose, but some required more injections or higher doses, or there was minor increase in rate of breakthrough; 3=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 and 4=Ineffective: routine failure to control hemostasis/hemostatic control require additional agents. Total number of scale responses =total count of scale responses for all participants; multiple responses per participant including those at scheduled and unscheduled visits are counted.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of rFIXFc. Data was summarized by treatment regimen for participants from Study 998HB102 and Study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

Arm/Group Title	rFIXFc (Participants From 9HB02PED)	rFIXFc (Participants From 998HB102)
Arm/Group Description	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of >5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg twice weekly versus 50 IU/kg once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	27	93
Measure Responses	151	815
Excellent	131	622
Effective	19	184
Partially Effective	1	9
Ineffective	0	0

7. Secondary Outcome

Title	Participant's Assessment of Response (Excellent or Good Response) to rFIXFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale
Description	Using eDiary, participant received rating for treatment response to any bleeding episode (BE) using 4-point scale- 1=Excellent: Abrupt pain relief and/or improvement in signs of bleeding within approximately (approx.) 8 hours (h) after initial injection (inj.); 2=Good: Definite pain relief and/or improvement in signs of bleeding within approx. 8h after an injection, but possibly requiring more than 1 injection after 24-48h for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8h after initial injection and requires more than 1 injection and 4=None: No improvement, or condition worsens within approx. 8h after initial injection. This assessment was to be made approx. 8 to 12h from time the injection was given to treat BE and prior to any additional doses of rFIXFc given for same bleeding episode. Percentages are based on the number of bleeding episodes for which a response (excellent or good) was provided for the first injection during the efficacy period.
Time Frame	Approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS was analyzed. Data was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.

Arm/Group Title	rFIXFc (9HB02PED [<6 Years Old Age Cohort])	rFIXFc (9HB02PED [6 to <12 Years Old Age Cohort])	rFIXFc (Participants From 998HB102)
Arm/Group Description	Participants with < 6 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants with 6 to <12 years old age received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of > 5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.
Measure Participants	13	14	93
Measure Injections	75	90	1646
Weekly Prophylaxis	60	47	342
Individualized Prophylaxis	25	336
Personalized Prophylaxis	0	1	135
Episodic	603

Adverse Events

Time Frame	From signing of Informed Consent Form (ICF) through follow-up (approximately 5 years)
Adverse Event Reporting Description	Adverse events (AEs) data was planned to be reported for each group and for the overall participants. AEs emergent during major surgical/rehabilitation periods are analyzed separately as per planned analysis and are presented as separate groups.
Arm/Group Title	rFIXFc (Participants From 9HB02PED)		rFIXFc (Participants From 998HB102)		Overall rFIXFc (Participants From 9HB02PED and 998HB102)		rFIXFc (Participants From 9HB02PED in Surgery Subgroup)		rFIXFc (Participants From 998HB102 in Surgery Subgroup)
Arm/Group Description	Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis (P): Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile in parent study and individual pharmacokinetic profile, trough and/or peak (recovery) values; Individualized P: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized P: included addition of prevention doses prior to strenuous activity; targeting FIX trough level of >5%, if warranted by bleeding history and/or activity level or dosing twice a week (25 IU/kg twice weekly versus 50 IU/kg once weekly) for participants who may have better control with such regimen. Participants who reached age of 12 during study could also choose to switch to episodic treatment group, with dosing based on participants clinical condition and type and severity of bleeding event.		Participants received rFIXFc IV according to their assigned treatment regimen as follows: Weekly prophylaxis: Participants received 20 IU/kg to 100 IU/kg rFIXFc once weekly. Dose was based on participants clinical profile observed in parent study and individual pharmacokinetic profile, trough, and/or peak (recovery) values. Individualized prophylaxis: 100 IU/kg rFIXFc every 8 to 16 days or twice a month; Personalized Prophylaxis: included addition of prevention doses prior to strenuous activity; targeting a FIX trough level of > 5%, if warranted by the bleeding history and/or activity level or dosing twice a week (25 IU/kg, twice weekly, versus 50 IU/kg, once weekly) for participants who may have better control with such a regimen. Episodic (On Demand): The individual dose of rFIXFc to treat bleeding episodes was based on participants clinical condition, type and severity of the bleeding event.		All participants who received rFIXFc drug in study 9HB01EXT, from studies 9HB02PED and 998HB102 (combined). AEs emergent during major surgical/rehabilitation periods are excluded and are presented as separate groups.		Participants who required emergent or elective surgery while participating in this study and treated with the dose and regimen of rFIXFc as appropriate for the type of surgery. Participants returned to a regular rFIXFc regimen once all dosing for the postoperative rehabilitation period had been completed.		Participants who required emergent or elective surgery while participating in this study and treated with the dose and regimen of rFIXFc as appropriate for the type of surgery. Participants returned to a regular rFIXFc regimen once all dosing for the postoperative rehabilitation period had been completed.
All Cause Mortality
	rFIXFc (Participants From 9HB02PED)		rFIXFc (Participants From 998HB102)		Overall rFIXFc (Participants From 9HB02PED and 998HB102)		rFIXFc (Participants From 9HB02PED in Surgery Subgroup)		rFIXFc (Participants From 998HB102 in Surgery Subgroup)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		0/15 (0%)
Serious Adverse Events
	rFIXFc (Participants From 9HB02PED)		rFIXFc (Participants From 998HB102)		Overall rFIXFc (Participants From 9HB02PED and 998HB102)		rFIXFc (Participants From 9HB02PED in Surgery Subgroup)		rFIXFc (Participants From 998HB102 in Surgery Subgroup)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)		31/93 (33.3%)		36/120 (30%)		0/1 (0%)		1/15 (6.7%)
Blood and lymphatic system disorders
Anaemia	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Eye disorders
Necrotising retinitis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Gastrointestinal disorders
Enterocolitis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Gastrointestinal haemorrhage	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Anal Sphincter Atony	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
General disorders
Pain	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Infections and infestations
Anal abscess	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Cellulitis	0/27 (0%)		3/93 (3.2%)		3/120 (2.5%)		0/1 (0%)		0/15 (0%)
Hepatitis C	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Orchitis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Pilonidal cyst	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Pneumonia	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Staphylococcal bacteraemia	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Tonsillitis	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Tooth abscess	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Wound infection	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Concussion	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Extradural haematoma	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Fall	3/27 (11.1%)		4/93 (4.3%)		7/120 (5.8%)		0/1 (0%)		0/15 (0%)
Femoral neck fracture	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Foreign body	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Head injury	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Laceration	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Post procedural haematoma	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Post procedural haemorrhage	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Rib fracture	0/27 (0%)		2/93 (2.2%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Road traffic accident	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Traumatic haematoma	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Traumatic intracranial haemorrhage	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Upper limb fracture	1/27 (3.7%)		0/93 (0%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Arthropathy	0/27 (0%)		2/93 (2.2%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Haemarthrosis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Haemophilic arthropathy	0/27 (0%)		4/93 (4.3%)		4/120 (3.3%)		0/1 (0%)		0/15 (0%)
Intervertebral disc protrusion	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Slipping rib syndrome	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Spinal column stenosis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Nervous system disorders
Epilepsy	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Haemorrhage intracranial	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Posterior interosseous syndrome	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Renal and urinary disorders
Calculus ureteric	0/27 (0%)		2/93 (2.2%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Haematuria	0/27 (0%)		2/93 (2.2%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Renal colic	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Renal failure acute	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Reproductive system and breast disorders
Epididymitis	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Tonsillar haemorrhage	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Social circumstances
Victim of crime	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Surgical and medical procedures
Knee arthroplasty	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Tonsillectomy	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Vascular disorders
Haematoma	0/27 (0%)		1/93 (1.1%)		1/120 (0.8%)		0/1 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	rFIXFc (Participants From 9HB02PED)		rFIXFc (Participants From 998HB102)		Overall rFIXFc (Participants From 9HB02PED and 998HB102)		rFIXFc (Participants From 9HB02PED in Surgery Subgroup)		rFIXFc (Participants From 998HB102 in Surgery Subgroup)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/27 (85.2%)		66/93 (71%)		89/120 (74.2%)		0/1 (0%)		4/15 (26.7%)
Gastrointestinal disorders
Diarrhoea	2/27 (7.4%)		4/93 (4.3%)		6/120 (5%)		0/1 (0%)		0/15 (0%)
Gingival bleeding	2/27 (7.4%)		0/93 (0%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Gastrooesophageal reflux disease	1/27 (3.7%)		7/93 (7.5%)		8/120 (6.7%)		0/1 (0%)		0/15 (0%)
Nausea	0/27 (0%)		5/93 (5.4%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Toothache	0/27 (0%)		5/93 (5.4%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Vomiting	5/27 (18.5%)		7/93 (7.5%)		12/120 (10%)		0/1 (0%)		0/15 (0%)
Food poisoning	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
General disorders
Pyrexia	6/27 (22.2%)		5/93 (5.4%)		11/120 (9.2%)		0/1 (0%)		0/15 (0%)
Immune system disorders
Seasonal allergy	4/27 (14.8%)		3/93 (3.2%)		7/120 (5.8%)		0/1 (0%)		0/15 (0%)
Infections and infestations
Ear infection	3/27 (11.1%)		1/93 (1.1%)		4/120 (3.3%)		0/1 (0%)		0/15 (0%)
Influenza	1/27 (3.7%)		8/93 (8.6%)		9/120 (7.5%)		0/1 (0%)		1/15 (6.7%)
Hepatitis C	0/27 (0%)		5/93 (5.4%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Lower respiratory tract infection	3/27 (11.1%)		1/93 (1.1%)		4/120 (3.3%)		0/1 (0%)		0/15 (0%)
Nasopharyngitis	3/27 (11.1%)		14/93 (15.1%)		17/120 (14.2%)		0/1 (0%)		0/15 (0%)
Paronychia	2/27 (7.4%)		0/93 (0%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Tonsillitis	2/27 (7.4%)		0/93 (0%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Sinusitis	1/27 (3.7%)		5/93 (5.4%)		6/120 (5%)		0/1 (0%)		0/15 (0%)
Upper respiratory tract infection	2/27 (7.4%)		6/93 (6.5%)		8/120 (6.7%)		0/1 (0%)		0/15 (0%)
Varicella	2/27 (7.4%)		1/93 (1.1%)		3/120 (2.5%)		0/1 (0%)		0/15 (0%)
Viral infection	2/27 (7.4%)		3/93 (3.2%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Excoriation	2/27 (7.4%)		1/93 (1.1%)		3/120 (2.5%)		0/1 (0%)		0/15 (0%)
Fall	7/27 (25.9%)		4/93 (4.3%)		11/120 (9.2%)		0/1 (0%)		0/15 (0%)
Head injury	2/27 (7.4%)		2/93 (2.2%)		4/120 (3.3%)		0/1 (0%)		0/15 (0%)
Joint dislocation	2/27 (7.4%)		0/93 (0%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Joint injury	2/27 (7.4%)		2/93 (2.2%)		4/120 (3.3%)		0/1 (0%)		0/15 (0%)
Ligament sprain	2/27 (7.4%)		4/93 (4.3%)		6/120 (5%)		0/1 (0%)		0/15 (0%)
Laceration	3/27 (11.1%)		5/93 (5.4%)		8/120 (6.7%)		0/1 (0%)		0/15 (0%)
Post Procedural Complication	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
Procedural Pain	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		2/15 (13.3%)
Investigations
Serum ferritin decreased	2/27 (7.4%)		0/93 (0%)		2/120 (1.7%)		0/1 (0%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/27 (14.8%)		10/93 (10.8%)		14/120 (11.7%)		0/1 (0%)		0/15 (0%)
Pain in extremity	2/27 (7.4%)		1/93 (1.1%)		3/120 (2.5%)		0/1 (0%)		0/15 (0%)
Nervous system disorders
Headache	3/27 (11.1%)		15/93 (16.1%)		18/120 (15%)		0/1 (0%)		0/15 (0%)
Convulsion	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
Psychiatric disorders
Insomnia	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
Stress	0/27 (0%)		0/93 (0%)		0/120 (0%)		0/1 (0%)		1/15 (6.7%)
Renal and urinary disorders
Haematuria	0/27 (0%)		5/93 (5.4%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/27 (11.1%)		5/93 (5.4%)		8/120 (6.7%)		0/1 (0%)		0/15 (0%)
Nasal congestion	5/27 (18.5%)		0/93 (0%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Epistaxis	5/27 (18.5%)		0/93 (0%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Acne	0/27 (0%)		5/93 (5.4%)		5/120 (4.2%)		0/1 (0%)		0/15 (0%)
Vascular disorders
Hypertension	0/27 (0%)		7/93 (7.5%)		7/120 (5.8%)		0/1 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.