Study to Determine the Safety and Efficacy of rFIXFc in Previously Untreated Males With Severe Hemophilia B (PUPs B-LONG)

• ClinicalTrials.gov Identifier: NCT02234310
• Recruitment Status: Completed
• First Posted: September 9, 2014
• Results First Posted: July 31, 2020
• Last Update Posted: July 31, 2020
• Sponsor: Bioverativ, a Sanofi company
• Collaborator: Swedish Orphan Biovitrum
• Information provided by (Responsible Party): Sanofi ( Bioverativ, a Sanofi company )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia B
• Intervention: Biological: rFIXFc
• Enrollment: 33

Participant Flow

Recruitment Details	The study was conducted at 28 active centers in 11 countries. Participants were screened between 13-Nov-2014 to 23-Jul-2018.
Pre-assignment Details	A total of 38 participants were screened. A total of 33 participants were enrolled, 22 participants began study participation on episodic treatment regimen and 11 participants began study participation on prophylactic treatment regimen.

Arm/Group Title	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description	Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (>=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Period Title: Overall Study
Started	33
Episodic Treatment Regimen	22 [1]
Prophylactic Treatment Regimen	28 [2]
Completed	27
Not Completed	6
Reason Not Completed
Physician Decision	1
Adverse Event	1
Eligibility Criteria not fulfilled	2
Withdrawal by Subject	2
[1] Participants were treated in more than one regimen and counted in all categories wherever applicable; [2] 17 participants among the 22 who started in episodic regimen, switched to the prophylactic regimen.

Baseline Characteristics

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Baseline Participants		33
Baseline Analysis Population Description		Analysis was performed on Safety Analysis Set which included all participants who received at least 1 dose of study rFIXFc.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	33 participants
		0.60; (0.08 to 2.00)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Female	0 0.0%
	Male	33 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	33 participants
White		22 66.7%
Black or African-American		1 3.0%
Asian		1 3.0%
American Indian or Alaska Native		0 0.0%
Native Hawaiian or other Pacific Islander		0 0.0%
Unknown or Not reported		5 15.2%
Other		4 12.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
Description	Development of an inhibitor was defined as an inhibitor test result of >= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of >=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on Safety Analysis set which included all participants who had received at least 1 dose of study treatment.

Arm/Group Title	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:	Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed	33
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	3.03; (0.08 to 15.76)

2. Secondary Outcome

Title	Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
Description	ABR was annualized number of bleeding episodes during efficacy period (EP) per participant normalized to a 1-year interval of time. Bleeding episodes were classified as: spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent strenuous activity; and traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens excluding surgical/rehabilitation periods and large injection intervals (greater than [>]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on Full Analysis Set (FAS) which included all enrolled participants with at least 1 dose of study treatment. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Median (Full Range); Unit of Measure: episodes per participant per year
Episodic regimen	Number Analyzed	22 participants
		0.21; (0.0 to 6.8)
Prophylaxis regimen	Number Analyzed	28 participants
		1.24; (0.0 to 5.4)

3. Secondary Outcome

Title	Annualized Number of Spontaneous Joint Bleeding Episodes
Description	Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there is no known contributing factor such as a definite trauma or antecedent "strenuous" activity. Annualized spontaneous joint bleeding episodes=(Total number of spontaneous joint bleeding episodes during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Median (Full Range); Unit of Measure: episodes per participant per year
Episodic regimen	Number Analyzed	22 participants
		0.00; (0.0 to 5.6)
Prophylaxis regimen	Number Analyzed	28 participants
		0.00; (0.0 to 2.6)

4. Secondary Outcome

Title	Number of rFIXFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Description	Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Analysis was based on all injections. Here, number analyzed signifies number of responses to injections reported for each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Overall Number of Units Analyzed; Type of Units Analyzed: Responses to injections		154
Count of Units; Unit of Measure: responses to injections
Episodic regimen	Number Analyzed	80 responses to injections
	Excellent or Good	22 27.5%
	Moderate	0 0.0%
	None	0 0.0%
	Response not provided	58 72.5%
Prophylaxis regimen	Number Analyzed	74 responses to injections
	Excellent or Good	50 67.6%
	Moderate	6 8.1%
	None	1 1.4%
	Response not provided	17 23.0%

5. Secondary Outcome

Title	Total Number of Exposure Days (EDs)
Description	An ED was defined as a 24-hour period in which a participant received one or more doses of rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant who did not have a particular injection type were counted as having zero injections for that type.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on safety analysis set.

Arm/Group Title	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:	Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed	33
Median (Full Range); Unit of Measure: days
	76.0; (1 to 137)

6. Secondary Outcome

Title	Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Description	Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (> 28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Median (Full Range); Unit of Measure: IU per kilogram per participant per year
Episodic regimen	Number Analyzed	22 participants
		203.2; (0 to 5719)
Prophylaxis regimen	Number Analyzed	28 participants
		3175.0; (2544 to 13164)

7. Secondary Outcome

Title	Number of Injections of rFIXFc Required to Resolve a Bleeding Episode
Description	Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding episodes		85
Median (Full Range); Unit of Measure: injections
Episodic regimen	Number Analyzed	27 Bleeding episodes [1]
		1.0; (1 to 31)
Prophylaxis regimen	Number Analyzed	58 Bleeding episodes [2]
		1.0; (1 to 4)

[1]

22 participants

[2]

28 participants

8. Secondary Outcome

Title	Average Dose Per Injection of rFIXFc Required to Resolve a Bleeding Episode
Description	The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Overall Number of Units Analyzed; Type of Units Analyzed: Bleeding episodes		85
Median (Full Range); Unit of Measure: IU/kg
Episodic regimen	Number Analyzed	27 Bleeding episodes [1]
		88.50; (41.7 to 178.6)
Prophylaxis regimen	Number Analyzed	58 Bleeding episodes [2]
		71.92; (23.3 to 181.8)

[1]

22 participants

[2]

28 participants

9. Secondary Outcome

Title	Change From Baseline in rFIXFc Incremental Recovery (IR)
Description	Blood samples were taken at trough and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX activity less than (<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
Time Frame	Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144

Outcome Measure Data

Analysis Population Description

Analysis performed on FAS. Here number analyzed signifies number of FAS participants with available data for each visit.

Arm/Group Title		Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description:		Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Overall Number of Participants Analyzed		33
Median (Inter-Quartile Range); Unit of Measure: IU/dL per IU/kg
Change at Week 12	Number Analyzed	14 participants
		0.0; (-0.08 to 0.12)
Change at Week 24	Number Analyzed	15 participants
		0.0; (-0.17 to 0.15)
Change at Week 36	Number Analyzed	18 participants
		-0.0; (-0.18 to 0.11)
Change at Week 48	Number Analyzed	20 participants
		-0.0; (-0.13 to 0.03)
Change at Week 60	Number Analyzed	17 participants
		-0.1; (-0.1 to 0.03)
Change at Week 72	Number Analyzed	12 participants
		-0.1; (-0.20 to 0.07)
Change at Week 84	Number Analyzed	10 participants
		-0.1; (-0.23 to -0.04)
Change at Week 96	Number Analyzed	7 participants
		-0.1; (-0.14 to 0.03)
Change at Week 108	Number Analyzed	4 participants
		-0.1; (-0.36 to -0.01)
Change at Week 120	Number Analyzed	1 participants
		-0.1; (-0.1 to -0.1)
Change at Week 132	Number Analyzed	1 participants
		-0.1; (-0.1 to -0.1)
Change at Week 144	Number Analyzed	1 participants
		0.0; (0.0 to 0.0)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 3 years) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AE are treatment-emergent AE i.e. AE that was present prior to receiving first injection of rFIXFc and subsequently worsened in severity, or was not present prior to receiving first injection but subsequently appeared before last visit/follow-up call, whichever came later. Analysis performed on safety analysis set.
Arm/Group Title	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Arm/Group Description	Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which >=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
All-Cause Mortality
	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
	Affected / at Risk (%)
Total	0/33 (0.00%)
Serious Adverse Events
	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
	Affected / at Risk (%)	# Events
Total	23/33 (69.70%)
Blood and lymphatic system disorders
Anaemia † 1	1/33 (3.03%)	1
Factor ix inhibition † 1	1/33 (3.03%)	1
Immune thrombocytopenic purpura † 1	1/33 (3.03%)	1
Congenital, familial and genetic disorders
Phimosis † 1	1/33 (3.03%)	1
Gastrointestinal disorders
Inguinal hernia † 1	1/33 (3.03%)	1
Tongue haemorrhage † 1	1/33 (3.03%)	1
General disorders
Vessel puncture site haematoma † 1	1/33 (3.03%)	1
Immune system disorders
Hypersensitivity † 1	1/33 (3.03%)	1
Infections and infestations
Croup infectious † 1	1/33 (3.03%)	1
Gastroenteritis † 1	1/33 (3.03%)	1
Infusion site pustule † 1	1/33 (3.03%)	1
Lower respiratory tract infection † 1	1/33 (3.03%)	1
Respiratory tract infection † 1	1/33 (3.03%)	1
Staphylococcal bacteraemia † 1	1/33 (3.03%)	1
Viral infection † 1	1/33 (3.03%)	1
Viral rash † 1	1/33 (3.03%)	1
Injury, poisoning and procedural complications
Accidental exposure to product † 1	1/33 (3.03%)	1
Craniocerebral injury † 1	1/33 (3.03%)	1
Face injury † 1	1/33 (3.03%)	1
Fall † 1	5/33 (15.15%)	9
Head injury † 1	3/33 (9.09%)	8
Skull fracture † 1	1/33 (3.03%)	1
Subdural haematoma † 1	1/33 (3.03%)	1
Musculoskeletal and connective tissue disorders
Compartment syndrome † 1	1/33 (3.03%)	1
Haemarthrosis † 1	1/33 (3.03%)	1
Nervous system disorders
Coma † 1	1/33 (3.03%)	1
Febrile convulsion † 1	1/33 (3.03%)	1
Spinal cord haematoma † 1	1/33 (3.03%)	1
Tongue biting † 1	1/33 (3.03%)	1
Reproductive system and breast disorders
Prepuce redundant † 1	1/33 (3.03%)	1
Surgical and medical procedures
Central venous catheterisation † 1	9/33 (27.27%)	9
Vascular disorders
Haematoma † 1	1/33 (3.03%)	1
Poor venous access † 1	3/33 (9.09%)	3
1 Term from vocabulary, MedDra 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
	Affected / at Risk (%)	# Events
Total	27/33 (81.82%)
Ear and labyrinth disorders
Middle ear effusion † 1	2/33 (6.06%)	2
Gastrointestinal disorders
Constipation † 1	2/33 (6.06%)	3
Diarrhoea † 1	5/33 (15.15%)	9
Teething † 1	6/33 (18.18%)	15
Vomiting † 1	4/33 (12.12%)	8
General disorders
Pyrexia † 1	14/33 (42.42%)	33
Infections and infestations
Bronchitis † 1	2/33 (6.06%)	4
Conjunctivitis † 1	2/33 (6.06%)	2
Croup infectious † 1	2/33 (6.06%)	2
Ear infection † 1	4/33 (12.12%)	4
Hand-foot-and-mouth disease † 1	2/33 (6.06%)	2
Influenza † 1	3/33 (9.09%)	3
Nasopharyngitis † 1	11/33 (33.33%)	22
Otitis media † 1	4/33 (12.12%)	8
Pharyngitis † 1	4/33 (12.12%)	5
Rhinitis † 1	3/33 (9.09%)	5
Upper respiratory tract infection † 1	7/33 (21.21%)	12
Varicella † 1	4/33 (12.12%)	4
Viral infection † 1	4/33 (12.12%)	6
Viral rash † 1	3/33 (9.09%)	3
Viral upper respiratory tract infection † 1	2/33 (6.06%)	3
Injury, poisoning and procedural complications
Contusion † 1	2/33 (6.06%)	2
Fall † 1	7/33 (21.21%)	13
Head injury † 1	5/33 (15.15%)	7
Investigations
Blood alkaline phosphatase increased † 1	3/33 (9.09%)	3
White blood cell count increased † 1	2/33 (6.06%)	2
Metabolism and nutrition disorders
Iron deficiency † 1	3/33 (9.09%)	4
Psychiatric disorders
Irritability † 1	2/33 (6.06%)	2
Reproductive system and breast disorders
Balanoposthitis † 1	2/33 (6.06%)	2
Respiratory, thoracic and mediastinal disorders
Asthma † 1	2/33 (6.06%)	3
Cough † 1	6/33 (18.18%)	11
Nasal congestion † 1	2/33 (6.06%)	2
Oropharyngeal pain † 1	3/33 (9.09%)	3
Rhinorrhoea † 1	6/33 (18.18%)	18
Skin and subcutaneous tissue disorders
Dermatitis diaper † 1	4/33 (12.12%)	5
Dry skin † 1	2/33 (6.06%)	2
Eczema † 1	3/33 (9.09%)	4
Erythema † 1	2/33 (6.06%)	2
Rash † 1	3/33 (9.09%)	4
1 Term from vocabulary, MedDra 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Bioverativ, a Sanofi company
• Phone: 800-633-1610 ext 6
• EMail: Contact-US@sanofi.com

• Responsible Party: Sanofi ( Bioverativ, a Sanofi company )
• ClinicalTrials.gov Identifier: NCT02234310
• Other Study ID Numbers: 998HB303; 2013-003629-27 ( EudraCT Number )
• First Submitted: July 17, 2014
• First Posted: September 9, 2014
• Results First Submitted: July 15, 2020
• Results First Posted: July 31, 2020
• Last Update Posted: July 31, 2020