Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B

• ClinicalTrials.gov Identifier: NCT01027364
• Recruitment Status: Completed
• First Posted: December 7, 2009
• Results First Posted: September 4, 2014
• Last Update Posted: December 19, 2020
• Sponsor: Bioverativ Therapeutics Inc.
• Collaborator: Swedish Orphan Biovitrum
• Information provided by (Responsible Party): Sanofi ( Bioverativ Therapeutics Inc. )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Severe Hemophilia B
• Interventions: Drug: Factor IX (rFIXFc); Drug: rFIX
• Enrollment: 123

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)	Arm 4: Perioperative Management
Arm/Group Description	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Period Title: Overall Study
Started	63	29	27	4 [1]
Enrolled in Sequential PK Subgroup	22	0	0	0
Joined Arm 4 for Surgery Then Returned	5	0	1	0
Started Arm 4 Then Joined Another Arm	2	0	0	0
Completed	59	27	26	3 [2]
Not Completed	4	2	1	1
Reason Not Completed
Adverse Event	1	0	1	0
Lost to Follow-up	1	0	0	0
Protocol Violation	1	0	0	1
Withdrawal by Subject	1	2	0	0
[1] 12 total participants in Arm 4 (6 started in Arm 4; 5 joined from Arm 1; 1 joined from Arm 3); [2] 11 participants total completed Arm 4 (3: compl. Arm 4 only; 7: cont. to Arm 1; 1: cont. to Arm 3)

Baseline Characteristics

Arm/Group Title		Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)	Arm 4: Perioperative Management	Total
Arm/Group Description		50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.	Total of all reporting groups
Overall Number of Baseline Participants		63	29	27	4	123
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	63 participants	29 participants	27 participants	4 participants	123 participants
		28.0; (12 to 71)	33.0; (12 to 62)	36.0; (14 to 64)	40.5; (30 to 61)	30.0; (12 to 71)
		[1] Measure Description: The 4 participants represented in the Perioperative Management arm includes participants who were enrolled in this arm only. A total of 12 participants underwent 14 major surgeries in this study, and 8 participants either joined this arm from another arm, or who started this arm, then joined another arm (see Participant Flow milestones for details).
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants	29 participants	27 participants	4 participants	123 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	63 100.0%	29 100.0%	27 100.0%	4 100.0%	123 100.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Description	Clinical laboratory evaluations included hematology and blood chemistry. Table does not include laboratory tests evaluated during the surgical/rehabilitation period. Because the perioperative management period represents a unique clinical situation, safety data obtained during the surgical/rehabilitation period for participants in Arm 4 were included in listings and reviewed separately. Review of the listing was sufficient to assess this endpoint. ULN=upper limit of normal.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of BeneFIX or rFIXFc; n=the number of participants with at least one post-baseline value. For this study, a table was not generated for potentially clinically significant laboratory abnormalities for participants in the perioperative management/surgical arm (Arm 4).

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	63	29	27
Measure Type: Number; Unit of Measure: participants
White Blood Cells <3.0*10^9/L; n=62, 28, 27	2	0	2
White Blood Cells >=16*10^9/L; n=62, 28, 27	0	0	0
Lymphocytes <0.8*10^9/L; n=60, 28, 26	1	2	3
Lymphocytes >12*10^9/L; n=60, 28, 26	0	0	0
Neutrophils <1.5*10^9/L; n=60, 28, 26	2	0	1
Neutrophils >13.5*10^9/L; n=60, 28, 26	0	0	0
Monocytes >2.5*10^9/L; n=60, 28, 26	0	0	0
Eosinophils >1.6*10^9/L; n=60, 28, 26	0	0	0
Basophils >1.6*10^9/L; n=60, 28, 26	0	0	0
Red Blood Cells <=3.5*10^12/L; n=62, 28, 27	1	0	0
Red Blood Cells >=6.4*10^12/L; n=62, 28, 27	0	0	0
Hemoglobin <=115 g/L; n=62, 28, 27	1	0	0
Hemoglobin >=190 g/L; n=62, 28, 27	0	0	0
Hematocrit <=37%; n=62, 28, 27	4	0	2
Hematocrit >=60%; n=62, 28, 27	0	0	0
Platelets <=75*10^9/L; n=62, 28, 27	0	0	1
Platelets >=700*10^9/L; n=62, 28, 27	0	0	0
Alanine Aminotransferase >=3*ULN; n=62, 28, 27	0	0	2
Aspartate Aminotransferase >=3*ULN; n=62, 28, 27	2	1	1
Alkaline Phosphatase >=3*ULN; n=62, 28, 27	0	0	0
Total Bilirubin >=34.2 µmol/L; n=62, 28, 27	1	0	0
Blood Urea Nitrogen >=10.7 mmol/L; n=62, 28, 27	1	0	0
Creatinine >=176.8 µmol/L; n=62, 28, 27	1	0	0
Sodium <=126 mmol/L; n=62, 28, 27	0	0	0
Sodium >=156 mmol/L; n=62, 28, 27	0	0	0
Potassium <=3 mmol/L; n=62, 28, 27	0	0	0
Potassium >=6 mmol/L; n=62, 28, 27	0	0	0
Chloride <=90 mmol/L; n=62, 28, 27	0	0	0
Chloride >=118 mmol/L; n=62, 28, 27	0	0	0
Phosphate <=0.55 mmol/L n=62, 28, 27	0	0	1
Phosphate >=1.71 mmol/L; n=62, 28, 27	1	1	0
Glucose <=2.22 mmol/L; n=62, 28, 27	0	0	0
Glucose >=9.71 mmol/L; n=62, 28, 27	4	1	0
Albumin <=25 g/L; n=62, 28, 27	0	0	0
Total Protein <=45 g/L; n=62, 28, 27	0	0	0
Total Protein >=100 g/L; n=62, 28, 27	0	0	0

2. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not. TE=event present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or not present prior to receiving the first injection but subsequently appeared before last visit on study. Serious AE (SAE)=AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event. Related=related, possibly related, and relationship missing. Data include AEs emergent during the surgical/rehabilitation period; AE data are included in each treatment arm only for the time each participant was enrolled in that arm.
Time Frame	up to 52 weeks + 30 days ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of BeneFIX or rFIXFc. A participant may have been in more than one group (i.e., participants in Arm 4 who were also in Arm 1, 2, or 3; please see Participant Flow for details). Participants with at least one TESAE reported are included in the TEAE count.

Arm/Group Title	Arm 1: Weekly Prophylaxis-BeneFIX	Arm 1: Weekly Prophylaxis-rFIXFc	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)	Arm 4: Perioperative Management
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	23	63	29	27	12
Measure Type: Number; Unit of Measure: participants
>=1 TEAE	2	45	23	20	10
>=1 Related TEAE	0	5	4	1	0
>=1 TESAE	0	5	4	4	3
>=1 Related TESAE	0	0	1	0	0

3. Primary Outcome

Title	Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) During the Surgical / Rehabilitation Period
Description	AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not. TEAE=AE present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or was not present prior to receiving the first injection but subsequently appeared before last visit on study. Participants are counted once if they report multiple events in the same system organ class (SOC) or preferred term (PT). Coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 15.0 dictionary. The following SOCs are abbreviated in the table: Immune System (IS); Injury, Poisoning, and Procedural (IPP); Metabolism and Nutrition (MN); Musculoskeletal and Connective Tissue (MCT); Respiratory, Thoracic and Mediastinal (RTM); Skin and Subcutaneous Tissue (SST).
Time Frame	up to 52 weeks + 30 days ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of BeneFIX or rFIXFc. A participant may have been in more than one group (i.e., participants in Arm 4 who were also in Arm 1, 2, or 3; please see Participant Flow for details).

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Participants With At Least 1 TEAE	8
Measure Type: Number; Unit of Measure: participants
SOC: Blood/Lymphatic System Disorders; PT: Anaemia	2
SOC: Ear and Labyrinth Disorders; PT: Vertigo	1
SOC: Gastrointestinal Disorders; PT: Constipation	1
SOC: Gastrointestinal Disorders; PT: Nausea	1
SOC: Gastrointestinal Disorders; PT: Vomiting	1
SOC: General Disorders; PT: Asthenia	1
SOC: General Disorders; PT: Infusion Site Pain	1
SOC: IS Disorders; PT: Drug Hypersensitivity	1
SOC: Infections/Infestations; PT: Cellulitis	1
SOC: IPP Complications; PT: Incision Site Pain	1
SOC: IPP Complications; PT: Procedural Pain	1
SOC: IPP Complications; PT: Wound Complication	1
SOC: Investigations; PT: Weight Increased	1
SOC: MN Disorders; PT: Decreased Appetite	1
SOC: MCT Disorders; PT: Muscle Spasms	1
SOC: Nervous System Disorders; PT: Dizziness	2
SOC: Nervous System Disorders; PT: Headache	1
SOC: Nervous System (NS) Disorders; PT: Neuralgia	1
SOC: NS Disorders; PT: Neuropathy Peripheral	1
SOC: Psychiatric Disorders; PT: Anxiety	1
SOC: Psychiatric Disorders; PT: Insomnia	1
SOC: RTM Disorders; PT: Dyspnoea	1
SOC: RTM Disorders; Oropharyngeal Pain	1
SOC: SST Disorders; PT: Hyperhidrosis	1
SOC: Vascular Disorders; PT: Hypertension	1
SOC: Vascular Disorders; PT: Hypotension	1

4. Primary Outcome

Title	Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Surgical / Rehabilitation Period
Description	SAE=AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event. TESAE=SAE present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or was not present prior to receiving the first injection but subsequently appeared before last visit on study. Participants are counted once if they report multiple events in the same system organ class (SOC) or preferred term (PT). Coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 15.0 dictionary. The following SOC is abbreviated in the table: Injury, Poisoning, and Procedural (IPP).
Time Frame	up to 52 weeks + 30 days ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of BeneFIX or rFIXFc. A participant may have been in more than one group (i.e., participants in Arm 4 who were also in Arm 1, 2, or 3; please see Participant Flow for details).

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Participants With At Least 1 TESAE	3
Measure Type: Number; Unit of Measure: participants
SOC: Cardiac Disorders; PT: Tachycardia	1
SOC: Infections/Infestations; PT: Bacterial Sepsis	1
SOC: Infections/Infestations; PT: Pilondial Cyst	1
SOC: Infections/Infestations; PT: Tooth Abscess	1
SOC: IPP Complications; PT: Limb Crushing Injury	1

5. Primary Outcome

Title	Incidence Rate of FIX Inhibitor Development
Description	An inhibitor test result ≥0.6 Bethesda units (BU)/mL, identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. The incidence rates along with the 95% CI were summarized for all titers for subjects with 50 or more exposure days (EDs) to rFIXFc and a valid inhibitor test after the 50th exposure. In addition, the incidence rates for all subjects regardless of their exposure days to rFIXFc were also summarized. The 95% CI was calculated using Clopper-Pearson exact method.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of of rFIXFc and who had a valid inhibitor test; n=number of participants with given number of exposure days who had a valid inhibitor test.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)	Arm 4: Perioperative Management	Total
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.	All participants from Arms 1-4
Overall Number of Participants Analyzed	63	27	27	4	121
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Participants with>=50 EDs to rFIXFc(n=52,2,0,1,55)	0; (0 to 6.85)	0; (0 to 84.19)	0 [1]; (NA to NA)	0; (0 to 97.50)	0; (0 to 6.49)
All participants (n=63, 27, 27, 4, 121)	0; (0 to 5.69)	0; (0 to 12.77)	0; (0 to 12.77)	0; (0 to 60.24)	0; (0 to 3.00)

[1]

n=0 for this arm

6. Primary Outcome

Title	Annualized Bleeding Rate
Description	Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)*365.25. In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed pharmacokinetic (PK) sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Median (Inter-Quartile Range); Unit of Measure: episodes per participant per year
	2.95; (1.01 to 4.35)	1.38; (0.00 to 3.43)	17.69; (10.77 to 23.24)

7. Primary Outcome

Title	Comparison of Annualized Bleeding Rates
Description	Estimated with a factor for arm, based on whole study duration for all participants. Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)*365.25. In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later. The EP was interrupted for the repeat PK period in Arm 1 and for all surgical/rehabilitation periods in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: episodes per participant per year
	3.12; (2.46 to 3.95)	2.40; (1.67 to 3.47)	18.67; (14.01 to 24.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: Weekly Prophylaxis, Arm 3: Episodic (On Demand)
	Comments	The null hypothesis for the primary endpoint is no difference between any prevention regimen and the on-demand regimen. The sample size of this study was mainly based on clinical rather than statistical considerations. However it was projected to have > 95% power at the 2-sided 0.05 level of significance, based upon this hypothesis test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	A hierarchical approach was applied to the comparison of the annualized bleeding rates between the prophylaxis arms and the episodic arm.
	Method	negative binomial model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Bleeding Rate Ratio
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.24
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm 2: Individualized Interval Prophylaxis, Arm 3: Episodic (On Demand)
	Comments	The null hypothesis for the primary endpoint is no difference between any prevention regimen and the on-demand regimen. The sample size of this study was mainly based on clinical rather than statistical considerations.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	A hierarchical approach was applied to the comparison of the annualized bleeding rates between the prophylaxis arms and the episodic arm.
	Method	negative binomial model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Bleeding Rate Ratio
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.20
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Participant Assessment of Response to Injections to Treat a Bleeding Episode
Description	Participant's assessment of the response to the first rFIXFc injection for each bleeding episode. Percentages were based on the number of bleeding episodes for which a response was provided for the first injection, using the following 4-point scale: 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 to 48 hours for complete resolution; moderate=probable or slight beneficial effect within 8 hours after the initial injection and requiring more than one injection; no response=no improvement, or condition worsened, within approximately 8 hours after the initial injection.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc and had a bleeding episode; participants with a non-evaluable bleeding episode are counted in the 'number of participants analyzed,' but not the percentages.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	47	15	27
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding Episodes	156	63	394
Measure Type: Number; Unit of Measure: percentage of responses
Excellent or Good	78.8	74.6	87.1
Excellent	35.3	31.7	37.3
Good	43.6	42.9	49.7
Moderate	18.6	22.2	11.9
No Response	2.6	3.2	1.0

9. Secondary Outcome

Title	Physicians' Global Assessments of Participants' Response to Treatment With rFIXFc
Description	Physicians assessed each participant's response to rFIXFc using a 4-point scale: excellent=bleeding episodes responded to less than or equal to the usual number of injections or less than or equal to the usual dose of rFIXFc, or the rate of breakthrough bleeding during prophylaxis was less than or equal to 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 bleeding; 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 required additional agents. Percentage of the total count of scale responses for all participants is presented. Multiple responses per participant are counted.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc, had evaluable efficacy assessments, and had nonmissing observations at time point.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Overall Number of Units Analyzed; Type of Units Analyzed: Responses	267	123	96
Measure Type: Number; Unit of Measure: percentage of responses
Excellent	74.5	73.2	58.3
Effective	24.3	26.0	39.6
Partially Effective	1.1	0.8	2.1
Ineffective	0	0	0

10. Secondary Outcome

Title	Annualized rFIXFc Consumption Per Participant
Description	Consumption is calculated for the efficacy period (EP). In Arms 1 and 2, the EP started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. Overall units (IU/kg) of annualized rFIXFc consumption = [Total rFIXFc IU/kg received during the EP / number of days in EP]*365.25.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc with evaluable data in the efficacy period. 'Overall' n=all participants in the Full Analysis Set with evaluable data in the efficacy period; 'Last 3 Months on Study' n=all participants in the Full Analysis Set with evaluable data and >=6 months on study.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Mean (Standard Deviation); Unit of Measure: IU/kg rFIXFc per participant per year
Overall (n=61, 26, 27)	2686.94 (825.969)	3371.92 (649.690)	936.70 (481.764)
Last 3 months on study (n=58, 26, 27)	2467.32 (978.529)	3497.78 (957.377)	957.73 (699.640)

11. Secondary Outcome

Title	Average Weekly Dose For the Fixed Weekly Interval Prophylaxis Arm
Description	Average weekly dose = (total IU/kg of all eligible prophylactic doses in the included intervals / total number of days in the included intervals)*7. Eligible dose = the first of the 2 doses defining the interval. Participants could have multiple prophylactic dose changes. Prophylactic dosing = from first prophylactic injection received for rFIXFc to the last prophylactic injection on study. Intervals between 2 prophylactic doses separated by a bleed/surgery/PK visit were not included. In Arm 1, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries).
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants in Arm 1 who received at least 1 dose of rFIXFc with evaluable data. 'Overall' n=participants with evaluable data; 'Last 3 Months on Study' n=participants with evaluable data and >=6 months on study.

Arm/Group Title	Arm 1: Weekly Prophylaxis
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.
Overall Number of Participants Analyzed	61
Mean (Standard Deviation); Unit of Measure: IU/kg
Overall (n=61)	46.26 (11.304)
Last 3 months on study (n=58)	43.10 (15.395)

12. Secondary Outcome

Title	Average Dosing Interval For the Individualized Interval Prophylaxis Arm
Description	Average dosing interval = sum of days in the included dosing intervals divided by the number of included intervals. Participants could have multiple prophylactic dose interval changes. Prophylactic dosing = from first prophylactic injection received for rFIXFc to the last prophylactic injection on study. Intervals between 2 prophylactic doses separated by a bleed/surgery/PK visit were not included. In Arm 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). The EP was interrupted for all surgical/rehabilitation periods (for both major and minor surgeries).
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants in Arm 2 who received at least 1 dose of rFIXFc with >=6 months on study and evaluable data.

Arm/Group Title	Arm 2: Individualized Interval Prophylaxis
Arm/Group Description:	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	26
Median (Inter-Quartile Range); Unit of Measure: days
Overall	12.53; (10.38 to 13.37)
Last 3 months on study	14.00; (11.29 to 14.00)

13. Secondary Outcome

Title	Annualized Bleeding Rate by Type of Bleed (Spontaneous and Traumatic)
Description	Annualized bleeding episodes = (number of bleeding episodes/number of days in efficacy period)*365.25. Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. Any bleeding at a different location was a separate bleeding episode regardless of time from the last injection.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc with evaluable data.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Median (Inter-Quartile Range); Unit of Measure: episodes per participant per year
Spontaneous	1.04; (0.00 to 2.19)	0.88; (0.00 to 2.30)	11.78; (2.62 to 19.78)
Traumatic	0.99; (0.00 to 2.13)	0.00; (0.00 to 0.78)	2.21; (0.00 to 6.81)
Unknown	0.00; (0.00 to 0.00)	0.00; (0.00 to 0.00)	0.00; (0.00 to 1.34)

14. Secondary Outcome

Title	Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa)
Description	Annualized bleeding episodes = (number of bleeding episodes/number of days in efficacy period)*365.25. Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. Any bleeding at a different location was a separate bleeding episode regardless of time from the last injection.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc with evaluable data.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	61	26	27
Median (Inter-Quartile Range); Unit of Measure: episodes per participant per year
Joint	1.11; (0.00 to 4.01)	0.36; (0.00 to 3.24)	13.58; (6.13 to 21.61)
Muscle	0.00; (0.00 to 1.04)	0.00; (0.00 to 0.00)	3.96; (1.02 to 6.79)
Internal	0.00; (0.00 to 0.00)	0.00; (0.00 to 0.00)	0.00; (0.00 to 1.31)
Skin/Mucosa	0.00; (0.00 to 0.00)	0.00; (0.00 to 0.00)	0.00; (0.00 to 1.14)

15. Secondary Outcome

Title	Number of Days From Last Injection to Treat a New Bleeding Episode
Description	Please see the definition of the Efficacy Period (EP) in the Outcome Measure 4 Description. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A follow-up injection administered >72 hours after the most recent injection given to treat a bleed was considered a new bleed at the same location and was classified as type=Unknown (bleeding episodes of this type were not evaluable). The first bleed for each participant could not be included in this analysis since there was no previous bleed from which to measure time. The number of days from the last injection to treat a bleed to a new bleeding episode was analyzed across all evaluable bleeding episodes per participant.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc and at least 1 evaluable bleeding episode.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	35	13	27
Overall Number of Units Analyzed; Type of Units Analyzed: Evaluable Bleeding Episodes	110	45	359
Median (Inter-Quartile Range); Unit of Measure: days
Per Bleeding Episode	40.78; (14.10 to 78.63)	39.48; (26.05 to 84.82)	13.42; (8.00 to 22.83)
Per Participant	59.52; (37.39 to 88.78)	76.13; (51.38 to 98.29)	19.67; (15.61 to 32.86)

16. Secondary Outcome

Title	Number of Injections Required for Resolution of a Bleeding Episode
Description	In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode). In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later. The EP was interrupted for the repeat PK period in Arm 1 and for all surgical/rehabilitation periods in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. All injections given from the initial sign of a bleed until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc and had at least 1 bleeding episode.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	47	15	27
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding Episodes	167	67	402
Median (Inter-Quartile Range); Unit of Measure: injections
Per Bleeding Episode	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)
Per Participant	1.00; (1.00 to 1.25)	1.09; (1.00 to 1.33)	1.04; (1.00 to 1.08)

17. Secondary Outcome

Title	Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed
Description	Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. All injections given from the initial sign of a bleed until the last date/time within the bleed window were counted. The resolution of a bleed was defined as no sign of bleeding following injection for the bleed. Bleeding episodes that presented in multiple locations are included as a single event in the overall summary for the number of injections to resolve that bleeding episode but are included in summaries for each location.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc, had a bleeding episode, and had evaluable efficacy assessments; n=total number of bleeds at given location.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	47	15	27
Median (Inter-Quartile Range); Unit of Measure: injections
Joint (n=125, 52, 314)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)
Muscle (n=35, 10, 90)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)
Internal (n=9, 3, 11)	1.0; (1.0 to 2.0)	2.0; (1.0 to 2.0)	1.0; (1.0 to 2.0)
Skin/Mucosa (n=11, 4, 21)	1.0; (1.0 to 2.0)	1.0; (1.0 to 1.0)	1.0; (1.0 to 1.0)

18. Secondary Outcome

Title	Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed
Description	For each bleeding episode at one location, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description. The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. Bleeding episodes that presented in multiple locations are included as a single event in the overall summary for dose administered to resolve that bleeding episode but are included in the individual summaries for each location.
Time Frame	up to 52 weeks ± 1 week (efficacy period as defined in description)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who received at least 1 dose of rFIXFc, had a bleeding episode, and had complete information on the dose administered to treat a bleeding episode; n=total number of bleeding episodes at this location.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	47	15	27
Median (Inter-Quartile Range); Unit of Measure: IU/kg
Joint (n=124, 52, 313)	50.14; (31.65 to 61.64)	45.29; (35.71 to 97.41)	46.73; (33.33 to 60.79)
Muscle (n=35, 10, 90)	55.56; (46.89 to 88.16)	67.17; (33.63 to 87.46)	46.57; (33.33 to 60.79)
Internal (n=9, 3, 11)	48.72; (41.67 to 125.00)	70.26; (33.63 to 131.72)	46.73; (33.33 to 61.07)
Skin/Mucosa (n=11, 4, 21)	46.89; (38.67 to 79.55)	48.48; (34.50 to 79.69)	22.22; (20.83 to 36.36)

19. Secondary Outcome

Title	Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 26
Description	The Haem-A-QoL consists of items pertaining to 10 domains specific to living with hemophilia and was administered to adult participants (> 17 years). The areas covered by this instrument are: physical health, feeling, view of yourself, sports/leisure, school/work, dealing with hemophilia, and treatment (all 7 domains, during the last month) and future, family planning, and outlook for the future (all 3 domains, recently). Changes from baseline for the Haem-A-QoL questionnaire are summarized by prestudy treatment regimen (pooled for Arms 1 and 2). Lower scores represent better QoL; therefore, a negative change from baseline represents improvement during the course of the study. Scores on a scale range between 0 and 100.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants in the 2 prophylaxis arms (Arms 1 and 2) over 17 years of age who received at least 1 dose of rFIXFc and had an assessment. n=participants who had specified assessment at given timepoint.

Arm/Group Title	Pre-study Regimen: Prophylaxis (Arms 1 and 2 Pooled)	Pre-study Regimen: On Demand (Arms 1 and 2 Pooled)
Arm/Group Description:	Participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had a prophylaxis pre-study regimen.	Participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had an on-demand pre-study regimen.
Overall Number of Participants Analyzed	27	31
Median (Full Range); Unit of Measure: units on a scale
Total Score (n=27, 26)	-6.82; (-22.8 to 6.1)	-6.25; (-25.5 to 12.8)
Physical Health (n=27, 31)	-10.00; (-45.0 to 20.0)	-15.00; (-60.0 to 15.0)
Feeling (n=27, 31)	0.00; (-43.8 to 50.0)	0.00; (-43.8 to 62.5)
View of Yourself (n=27, 30)	-5.00; (-25.0 to 15.0)	-5.00; (-35.0 to 25.0)
Sports and Leisure (n=22, 21)	-7.50; (-70.0 to 25.0)	-20.0; (-40.0 to 35.0)
Work and School (n=22, 25)	0.00; (-31.3 to 52.1)	-6.25; (-31.3 to 18.8)
Dealing with Hemophilia (n=27, 31)	0.00; (-100.0 to 100.0)	-8.33; (-66.7 to 75.0)
Treatment (n=27, 31)	-6.25; (-18.8 to 18.8)	0.00; (-53.1 to 37.5)
Future (n=26, 30)	-5.00; (-25.0 to 10.0)	0.00; (-30.0 to 20.0)
Family Planning (n=15, 13)	0.00; (-29.2 to 12.5)	0.00; (-43.8 to 25.0)
Partnership and Sexuality (n=26, 30)	0.00; (-50.0 to 66.7)	0.00; (-25.0 to 25.0)

20. Secondary Outcome

Title	Haem-A-QoL Questionnaire for Adults: Change From Baseline to Week 52
Description	The Haem-A-QoL consists of items pertaining to 10 domains specific to living with hemophilia and was administered to adult participants (> 17 years). The areas covered by this instrument are: physical health, feeling, view of yourself, sports/leisure, school/work, dealing with hemophilia, and treatment (all 7 domains, during the last month) and future, family planning, and outlook for the future (all 3 domains, recently). Changes from baseline for the Haem-A-QoL questionnaire are summarized by prestudy treatment regimen (pooled for Arms 1 and 2). Lower scores represent better QoL; therefore, a negative change from baseline represents improvement during the course of the study. Scores on a scale range between 0 and 100.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants in the 2 prophylaxis arms (Arms 1 and 2) over 17 years of age who received at least 1 dose of rFIXFc and had an assessment. n=participants who had specified assessment at given timepoint.

Arm/Group Title	Pre-study Regimen: Prophylaxis (Arms 1 and 2 Pooled)	Pre-study Regimen: On Demand (Arms 1 and 2 Pooled)
Arm/Group Description:	Participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had a prophylaxis pre-study regimen.	Participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had an on-demand pre-study regimen.
Overall Number of Participants Analyzed	27	24
Median (Full Range); Unit of Measure: units on a scale
Total Score (n=25, 19)	-4.35; (-24.4 to 9.6)	-6.06; (-31.0 to 1.0)
Physical Health (n=26, 23)	-10.00; (-45.0 to 20.0)	-15.00; (-60.0 to 0.0)
Feeling (n=26, 23)	0.00; (-37.5 to 75.0)	0.00; (-50.0 to 18.8)
View of Yourself (n=26, 24)	-7.50; (-45.0 to 20.0)	-5.00; (-35.0 to 15.0)
Sports and Leisure (n=20, 16)	-0.62; (-55.0 to 27.5)	-17.50; (-55.0 to 17.5)
Work and School (n=22, 20)	0.00; (-31.3 to 25.0)	-3.13; (-41.7 to 25.0)
Dealing with Hemophilia (n=27, 24)	0.00; (-66.7 to 33.3)	4.17; (-66.7 to 66.7)
Treatment (n=27, 24)	-6.25; (-30.8 to 15.6)	-4.69; (-34.4 to 34.4)
Future (n=26, 23)	-5.00; (-40.0 to 20.0)	-5.00; (-40.0 to 15.0)
Family Planning (n=14, 11)	0.00; (-25.0 to 33.3)	0.00; (-12.5 to 12.5)

21. Secondary Outcome

Title	Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 26 and Week 52
Description	The Haemo-QoL, a quality of life (QoL) assessment instrument for children and adolescents with hemophilia, was administered to participants from 13- to 17-years-old. This instrument assesses domains specific to living with hemophilia. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.
Time Frame	Baseline, Week 26, Week 52

Outcome Measure Data

Analysis Population Description

No summary analysis was done for this outcome measure due to the small number of participants completing the questionnaire.

Arm/Group Title	Pre-study Regimen: Prophylaxis (Arms 1 and 2 Pooled)	Pre-study Regimen: On Demand (Arms 1 and 2 Pooled)
Arm/Group Description:	Child and adolescent participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had a prophylaxis pre-study regimen.	Child and adolescent participants from the Weekly or Individualized Interval Prophylaxis Arms (Arms 1 or 2) who had an on-demand pre-study regimen.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

22. Secondary Outcome

Title	Investigators'/Surgeons' Assessment of Participants' Response to rFIXFc for Major Surgery
Description	Based on the first assessment of hemostasis by the surgeon/investigator 24 hours or later post-surgery. Scaled responses: Excellent = 1, Good = 2, Fair = 3, Poor/none = 4.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Participants in Arm 4 who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Major Surgeries	14
Measure Type: Number; Unit of Measure: responses
Excellent or Good	14
Excellent	13
Good	1
Fair	0
Poor/None	0

23. Secondary Outcome

Title	Number of Injections Required to Maintain Hemostasis During Major Surgery
Description	The number of injections to maintain hemostasis during surgery includes all injections for surgery purposes including the loading dose to the end date/time of surgery.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Participants in Arm 4 who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Major Surgeries	14
Median (Full Range); Unit of Measure: injections
	1.00; (1.0 to 4.0)

24. Secondary Outcome

Title	Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery
Description	Mean dose per injection is the average dose for all injections (including loading dose) needed to maintain hemostasis during surgery. Total dose is the sum across all injections (including loading dose) needed to maintain hemostasis during surgery.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Participants in Arm 4 who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Major Surgeries	14
Median (Full Range); Unit of Measure: IU/kg
Dose per Injection	90.91; (49.4 to 142.3)
Total Dose	102.59; (49.4 to 264.5)

25. Secondary Outcome

Title	Estimated Total Blood Loss During Major Surgery
Description	[Not Specified]
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Participants in Arm 4 who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Major Surgeries	14
Median (Full Range); Unit of Measure: mL
	65.50; (0.0 to 300.0)

26. Secondary Outcome

Title	Number of Transfusions Required Per Surgery
Description	Number of blood component transfusions during a single surgery.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Participants in Arm 4 who received at least 1 dose of rFIXFc.

Arm/Group Title	Arm 4: Perioperative Management
Arm/Group Description:	The surgical period and dosing were dependent on the type of surgery the participant underwent. Participants who started the study in one of the other treatment arms prior to surgery returned to the original treatment arm. Participants who joined the study in the Surgery arm were assigned to one of the other treatment arms following post-operative rehabilitation.
Overall Number of Participants Analyzed	12
Overall Number of Units Analyzed; Type of Units Analyzed: Major Surgeries	14
Measure Type: Number; Unit of Measure: surgeries
0 transfusions	12
1 transfusion	0
2 transfusions	1
3 transfusions	0
>3 transfusions	1

27. Secondary Outcome

Title	Maximum Concentration (Cmax)
Description	Maximum concentration during a dosing interval. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: IU/dL
rFIXFc Baseline	40.81; (33.60 to 49.58)
BeneFIX	43.08; (36.69 to 50.59)

28. Secondary Outcome

Title	Area Under the Curve (AUC) Per Dose
Description	Dose normalized area under the drug concentration-time curve. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: IU*h/dL per IU/kg
rFIXFc Baseline	31.32; (27.88 to 35.18)
BeneFIX	15.77; (14.02 to 17.74)

29. Secondary Outcome

Title	Half Life (t1/2) Alpha and t1/2 Beta
Description	Time required for the concentration of the drug to reach half of its original value. Alpha and beta half-life indicate distribution and elimination half-life in a two-compartment PK model. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: hours
rFIXFc Baseline: t1/2 alpha	5.0279; (3.2032 to 7.8919)
BeneFIX: t1/2 alpha	2.4113; (1.6183 to 3.5930)
rFIXFc Baseline: t1/2 beta	82.12; (71.39 to 94.46)
BeneFIX: t1/2 beta	33.77; (29.13 to 39.15)

30. Secondary Outcome

Title	Clearance (CL)
Description	The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: mL/h/kg
rFIXFc Baseline	3.193; (2.843 to 3.587)
BeneFIX	6.340; (5.637 to 7.131)

31. Secondary Outcome

Title	Mean Residence Time (MRT)
Description	The average time for all the drug molecules to reside in the body. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: hours
rFIXFc Baseline	98.60; (88.16 to 110.29)
BeneFIX	41.19; (35.98 to 47.15)

32. Secondary Outcome

Title	Volume in Steady State (Vss)
Description	Volume of distribution at steady state. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: mL/kg
rFIXFc Baseline	314.8; (277.8 to 356.8)
BeneFIX	261.1; (222.9 to 305.9)

33. Secondary Outcome

Title	Incremental Recovery
Description	IU/dL rise in plasma per IU/kg drug administered. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: IU/dL per IU/kg
rFIXFc Baseline	0.9211; (0.7710 to 1.1004)
BeneFIX	0.9451; (0.8149 to 1.0961)

34. Secondary Outcome

Title	Time to 1% and 3% FIX Activity
Description	Time to reach 1 or 3 IU/dL (%) after a single dose. Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection. Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
Time Frame	See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.

Outcome Measure Data

Analysis Population Description

Participants in the Sequential PK Subgroup who have evaluable PK profiles for both BeneFIX and baseline rFIXFc.

Arm/Group Title	Arm 1: Weekly Prophylaxis - Sequential PK Subgroup
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	22
Geometric Mean (95% Confidence Interval); Unit of Measure: days
rFIXFc Baseline: 1% Activity	11.224; (10.200 to 12.350)
BeneFIX: 1% Activity	5.087; (4.579 to 5.651)
rFIXFc Baseline: 3% Activity	5.767; (5.066 to 6.565)
BeneFIX: 3% Activity	2.832; (2.568 to 3.123)

35. Secondary Outcome

Title	Number of Participants With Clinically Relevant Abnormalities or Relevant Changes From Baseline in Vital Signs
Description	Number of participants with clinically relevant abnormalities or relevant changes from baseline in temperature, pulse (beats per minute [bpm]), systolic blood pressure (SBP), and diastolic blood pressure (DBP) are presented. Baseline (BL) is defined as the last non-missing evaluable assessment taken prior and closest to the first rFIXFc dose. Because the perioperative management period represents a unique clinical situation, safety data obtained during the surgical/rehabilitation period for participants in Arm 4 were included in listings and reviewed separately. Review of the listing was sufficient to assess this endpoint.
Time Frame	up to 52 weeks ± 1 week

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who received at least 1 dose of BeneFIX or rFIXFc; a table was not generated for participants in the perioperative management/surgical arm (Arm 4). n=participants with a baseline assessment and at least one post-baseline assessment for temperature or at least one post-baseline assessment for pulse, SBP, and DBP.

Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description:	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
Overall Number of Participants Analyzed	63	29	27
Measure Type: Number; Unit of Measure: participants
Temperature: >38°C and ≥1°C ↑ from BL, n=61,28,24	0	0	0
Pulse: >120 bpm or >20 bpm ↑ from BL, n=62,28,24	1	2	0
Pulse: <50 bpm or >20 bpm ↓ from BL, n=62,28,24	2	1	0
SBP: >180 mm Hg or >40 mm Hg ↑ from BL, n=62,28,24	0	1	0
SBP: <90 mm Hg or >30 mm Hg ↓ from BL, n=62,28,24	4	1	0
DBP: >105 mm Hg or >30 mm Hg ↑ from BL, n=62,28,24	3	0	0
DBP: <50 mm Hg or >20 mm Hg ↓ from BL, n=62,28,24	5	4	0

36. Secondary Outcome

Title	Coagulation Parameter: Change From Pre-dose Values in Prothrombin Split Fragments 1+ 2 (F 1+2)
Description	Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
Time Frame	Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)

Outcome Measure Data

Analysis Population Description

The Sequential PK subgroup consisted of all participants who had evaluable PK profiles for both BeneFIX and baseline rFIXFc, and/or evaluable PK profiles for both baseline and repeat rFIXFc at Week 26 (±1 week). n=participants with an assessment at given time point.

Arm/Group Title	Sequential PK Subgroup: BeneFIX	Sequential PK Subgroup: rFIXFc Day 1	Sequential PK Subgroup: rFIXFc Week 26	Sequential PK Subgroup: rFIXFc Week 52
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	23	23	23	23
Mean (Standard Deviation); Unit of Measure: pmol/L
Pre-dosing Value (n=23, 23, 20, 19)	134.1 (64.93)	130.0 (57.55)	131.6 (42.43)	176.7 (112.36)
Change at 1 Hour Post-dosing (n=23, 22, 20, 0)	73.4 (171.68)	8.6 (39.14)	1.3 (51.64)	NA [1] (NA)
Change at 6 Hours Post-dosing (n=23, 22, 20, 0)	7.8 (55.45)	8.3 (38.66)	-4.4 (45.95)	NA [1] (NA)
Change at 24 Hours Post-dosing (n=23, 22, 18, 0)	-3.7 (34.39)	9.8 (45.62)	1.7 (27.14)	NA [1] (NA)
Maximum Post-dosing Change (n=23, 23, 19, 0)	83.0 (168.71)	30.9 (48.52)	20.4 (49.38)	NA [1] (NA)

[1]

assessment was not done at this time point

37. Secondary Outcome

Title	Coagulation Parameter: Change From Pre-dose Values in Thrombin-antithrombin (TAT) Complex
Description	Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
Time Frame	Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)

Outcome Measure Data

Analysis Population Description

The Sequential PK subgroup consisted of all participants who had evaluable PK profiles for both BeneFIX and baseline rFIXFc, and/or evaluable PK profiles for both baseline and repeat rFIXFc at Week 26 (±1 week). n=participants with an assessment at given time point.

Arm/Group Title	Sequential PK Subgroup: BeneFIX	Sequential PK Subgroup: rFIXFc Day 1	Sequential PK Subgroup: rFIXFc Week 26	Sequential PK Subgroup: rFIXFc Week 52
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	23	23	23	23
Mean (Standard Deviation); Unit of Measure: ng/mL
Pre-dosing Value (n=23, 23, 20, 19)	2.87 (2.891)	2.87 (2.230)	3.11 (4.075)	4.28 (7.588)
Change at 1 Hour Post-dosing (n=23, 22, 20, 0)	6.67 (15.491)	1.05 (4.019)	0.11 (5.813)	NA [1] (NA)
Change at 6 Hours Post-dosing (n=23, 22, 20, 0)	1.91 (7.303)	1.07 (4.686)	-0.09 (5.763)	NA [1] (NA)
Change at 24 Hours Post-dosing (n=23, 22, 18, 0)	-0.58 (2.968)	0.81 (6.095)	-1.10 (4.308)	NA [1] (NA)
Maximum Post-dosing Change (n=23, 23, 19, 0)	7.42 (15.416)	3.63 (7.000)	0.32 (5.969)	NA [1] (NA)

[1]

assessment was not done at this time point

38. Secondary Outcome

Title	Coagulation Parameter: Change From Pre-dose Values in D-dimer
Description	Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
Time Frame	Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)

Outcome Measure Data

Analysis Population Description

The Sequential PK subgroup consisted of all participants who had evaluable PK profiles for both BeneFIX and baseline rFIXFc, and/or evaluable PK profiles for both baseline and repeat rFIXFc at Week 26 (±1 week). n=participants with an assessment at given time point.

Arm/Group Title	Sequential PK Subgroup: BeneFIX	Sequential PK Subgroup: rFIXFc Day 1	Sequential PK Subgroup: rFIXFc Week 26	Sequential PK Subgroup: rFIXFc Week 52
Arm/Group Description:	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.	Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. All participants in Arm 1 received 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.
Overall Number of Participants Analyzed	23	23	23	23
Mean (Standard Deviation); Unit of Measure: ng/mL
Pre-dosing Value (n=23, 22, 20, 19)	153.0 (119.37)	176.2 (165.48)	120.5 (73.38)	134.7 (151.36)
Change at 1 Hour Post-dosing (n=23, 21, 20, 0)	35.9 (101.80)	89.6 (509.24)	-5.9 (28.18)	NA [1] (NA)
Change at 6 Hours Post-dosing (n=23, 21, 20, 0)	47.6 (259.70)	-39.6 (134.42)	-9.4 (16.84)	NA [1] (NA)
Change at 24 Hours Post-dosing (n=23, 21, 18, 0)	20.0 (85.93)	-31.0 (138.22)	-8.2 (26.06)	NA [1] (NA)
Maximum Post-dosing Change (n=23, 22, 19, 0)	95.7 (266.98)	100.6 (494.70)	4.8 (16.10)	NA [1] (NA)

[1]

assessment was not done at this time point

Adverse Events

Time Frame	up to 52 weeks + 30 days ± 1 week
Adverse Event Reporting Description	As the perioperative management period represents a unique clinical situation, safety data obtained during the surgical/rehabilitation period for Arm 4 subjects were analyzed separately per the Analysis Plan, and not included within the Arms 1-3 analysis. See Outcome Measures 3 and 4 for AE/SAE data for the surgical/rehabilitation period, Arm 4.
Arm/Group Title	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
Arm/Group Description	50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.	100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.	20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
All-Cause Mortality
	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/63 (7.94%)	4/29 (13.79%)	4/27 (14.81%)
Cardiac disorders
Angina pectoris † 1	1/63 (1.59%)	0/29 (0.00%)	0/27 (0.00%)
Gastrointestinal disorders
Abdominal adhesions † 1	1/63 (1.59%)	0/29 (0.00%)	0/27 (0.00%)
Inguinal hernia † 1	0/63 (0.00%)	0/29 (0.00%)	1/27 (3.70%)
Intestinal obstruction † 1	0/63 (0.00%)	0/29 (0.00%)	1/27 (3.70%)
Small intestinal obstruction † 1	0/63 (0.00%)	0/29 (0.00%)	1/27 (3.70%)
Upper gastrointestinal haemorrhage † 1	0/63 (0.00%)	1/29 (3.45%)	0/27 (0.00%)
Infections and infestations
Cellulitis † 1	1/63 (1.59%)	0/29 (0.00%)	1/27 (3.70%)
Device related infection † 1	1/63 (1.59%)	0/29 (0.00%)	0/27 (0.00%)
Peritonsillar abscess † 1	0/63 (0.00%)	1/29 (3.45%)	0/27 (0.00%)
Injury, poisoning and procedural complications
Road traffic accident † 1	0/63 (0.00%)	0/29 (0.00%)	1/27 (3.70%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/63 (1.59%)	0/29 (0.00%)	0/27 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant † 1	0/63 (0.00%)	1/29 (3.45%)	0/27 (0.00%)
Renal and urinary disorders
Obstructive uropathy † 1	0/63 (0.00%)	1/29 (3.45%)	0/27 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm 1: Weekly Prophylaxis	Arm 2: Individualized Interval Prophylaxis	Arm 3: Episodic (On Demand)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	29/63 (46.03%)	17/29 (58.62%)	11/27 (40.74%)
Gastrointestinal disorders
Nausea † 1	1/63 (1.59%)	2/29 (6.90%)	0/27 (0.00%)
Immune system disorders
Allergy to arthropod bite † 1	0/63 (0.00%)	2/29 (6.90%)	0/27 (0.00%)
Infections and infestations
Nasopharyngitis † 1	13/63 (20.63%)	4/29 (13.79%)	1/27 (3.70%)
Influenza † 1	5/63 (7.94%)	0/29 (0.00%)	4/27 (14.81%)
Upper respiratory tract infection † 1	4/63 (6.35%)	2/29 (6.90%)	1/27 (3.70%)
Sinusitis † 1	3/63 (4.76%)	2/29 (6.90%)	0/27 (0.00%)
Injury, poisoning and procedural complications
Laceration † 1	1/63 (1.59%)	2/29 (6.90%)	0/27 (0.00%)
Investigations
Weight increased † 1	1/63 (1.59%)	0/29 (0.00%)	2/27 (7.41%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/63 (9.52%)	2/29 (6.90%)	0/27 (0.00%)
Musculoskeletal pain † 1	2/63 (3.17%)	2/29 (6.90%)	0/27 (0.00%)
Back pain † 1	0/63 (0.00%)	1/29 (3.45%)	2/27 (7.41%)
Nervous system disorders
Headache † 1	2/63 (3.17%)	2/29 (6.90%)	2/27 (7.41%)
Dizziness † 1	3/63 (4.76%)	2/29 (6.90%)	0/27 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/63 (0.00%)	0/29 (0.00%)	3/27 (11.11%)
Vascular disorders
Hypertension † 1	3/63 (4.76%)	2/29 (6.90%)	1/27 (3.70%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Bioverativ Study Medical Director
• Organization: Bioverativ
• EMail: clinicaltrials@bioverativ.com

Publications of Results:

Powell JS, Pasi KJ, Ragni MV, Ozelo MC, Valentino LA, Mahlangu JN, Josephson NC, Perry D, Manco-Johnson MJ, Apte S, Baker RI, Chan GC, Novitzky N, Wong RS, Krassova S, Allen G, Jiang H, Innes A, Li S, Cristiano LM, Goyal J, Sommer JM, Dumont JA, Nugent K, Vigliani G, Brennan A, Luk A, Pierce GF; B-LONG Investigators. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013 Dec 12;369(24):2313-23. doi: 10.1056/NEJMoa1305074. Epub 2013 Dec 4.

• Responsible Party: Sanofi ( Bioverativ Therapeutics Inc. )
• ClinicalTrials.gov Identifier: NCT01027364
• Other Study ID Numbers: 998HB102; 2009-014295-21 ( EudraCT Number )
• First Submitted: December 4, 2009
• First Posted: December 7, 2009
• Results First Submitted: April 14, 2014
• Results First Posted: September 4, 2014
• Last Update Posted: December 19, 2020