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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01027364
Recruitment Status : Completed
First Posted : December 7, 2009
Results First Posted : September 4, 2014
Last Update Posted : September 25, 2018
Sponsor:
Collaborator:
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
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
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
Hide 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)
Arm/Group Title Arm 1: Weekly Prophylaxis Arm 2: Individualized Interval Prophylaxis Arm 3: Episodic (On Demand) Arm 4: Perioperative Management Total
Hide 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
Hide 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%
1.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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)
Show Statistical Analysis 1 Hide 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
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]
Show Statistical Analysis 2 Hide 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
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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
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Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
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Hide 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)
Hide 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
Hide 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
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Hide Analysis Population Description
Participants in Arm 4 who received at least 1 dose of rFIXFc.
Arm/Group Title Arm 4: Perioperative Management
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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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Arm 4 who received at least 1 dose of rFIXFc.
Arm/Group Title Arm 4: Perioperative Management
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Arm 4 who received at least 1 dose of rFIXFc.
Arm/Group Title Arm 4: Perioperative Management
Hide 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
Hide Description [Not Specified]
Time Frame up to 52 weeks ± 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Arm 4 who received at least 1 dose of rFIXFc.
Arm/Group Title Arm 4: Perioperative Management
Hide 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
Hide Description Number of blood component transfusions during a single surgery.
Time Frame up to 52 weeks ± 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Arm 4 who received at least 1 dose of rFIXFc.
Arm/Group Title Arm 4: Perioperative Management
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
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)
Hide 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   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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
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
Responsible Party: Bioverativ Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01027364     History of Changes
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: September 25, 2018