Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open Label Study to Determine the Safety and Efficacy of Replacement Factor VIII Protein (Known as rFVIIIFc) in Previously Untreated Males With Severe Hemophilia A

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: NCT02234323
Recruitment Status : Completed
First Posted : September 9, 2014
Results First Posted : August 13, 2020
Last Update Posted : August 13, 2020
Sponsor:
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 A
Intervention Biological: rFVIIIFc
Enrollment 108
Recruitment Details The study was conducted at 44 active centers in 13 countries between 12-Jan-2015 to 23-Sep-2019.
Pre-assignment Details 110 participants screened, 108 enrolled, 103 received drug.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description Participants were to receive rFVIIIFc as follows -Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3-5 day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 Bethesda Units per milliliter [BU/mL]) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Period Title: All Enrolled
Started 108
Completed 103 [1]
Not Completed 5
Reason Not Completed
Not Treated: Completed study in database             2
Not Treated:Consent withdrawn by subject             2
Not Treated: Exceeded lab value limit             1
[1]
These participants received at least one dose of study drug.
Period Title: All Treated
Started 103
Episodic Treatment Regimen 81 [1]
Prophylactic Treatment Regimen 89 [2]
Immune Tolerance Induction (ITI) 15 [3]
Completed 85
Not Completed 18
Reason Not Completed
Death             1
Physician Decision             5
Lack of Efficacy             3
Exceeded lab value limit             2
Other             7
[1]
Participants were treated in more than one regimen and counted in all categories wherever applicable
[2]
69 participants among the 81 who started in episodic regimen, switched to the prophylactic regimen.
[3]
1/81 on episodic and 14/89 on prophylactic regimen had inhibitors and were switched directly to ITI.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Baseline Participants 103
Hide Baseline Analysis Population Description
The safety analysis set was defined as all participants who received at least 1 dose of rFVIIIFc.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 103 participants
0.58
(0.02 to 4.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Female
0
   0.0%
Male
103
 100.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
White
79
  76.7%
Black or African-American
2
   1.9%
Asian
5
   4.9%
Native Hawaiian or other Pacific Islander
2
   1.9%
Not reported due to confidentiality regulations
4
   3.9%
Other
11
  10.7%
1.Primary Outcome
Title Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
Hide Description A positive/confirmed inhibitor result occurs when a participant has a value >=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected >=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached >=10 EDs and had >=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received >=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set participants who 1) reached >=10 EDs and had >=1 inhibitor test performed at >=10 EDs or who had inhibitor or 2) did not develop inhibitor but reached >=10 EDs or 3) developed an inhibitor following the initial rFVIIIFc administration.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR (Prophylaxis regimen): rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.11
(21.77 to 41.74)
2.Secondary Outcome
Title Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
Hide Description ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized 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 as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on Full Analysis Set (FAS) participants within the EP. FAS included all enrolled participants with >=1 dose of study treatment. Here, number analyzed signifies number of FAS participants analyzed in each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Full Range)
Unit of Measure: episodes per participant per year
Episodic Treatment Number Analyzed 81 participants
2.24
(0.0 to 39.8)
Prophylaxis Treatment Number Analyzed 89 participants
1.49
(0.0 to 18.7)
ITI Treatment Number Analyzed 15 participants
0.00
(0.0 to 6.6)
3.Secondary Outcome
Title Annualized Number of Spontaneous Joint Bleeding Episodes
Hide Description Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was 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 EP divided by total number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (> 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS which included participants within EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Inter-Quartile Range)
Unit of Measure: episodes per participant per year
Episodic Treatment Number Analyzed 81 participants
0.00
(0.0 to 0.0)
Prophylaxis Treatment Number Analyzed 89 participants
0.00
(0.0 to 0.0)
ITI Treatment Number Analyzed 15 participants
0.00
(0.0 to 0.0)
4.Secondary Outcome
Title Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Hide Description Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on FAS participants within the EP and based on all injections. Here, number analyzed signifies number of responses to injections reported for each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Overall Number of Units Analyzed
Type of Units Analyzed: Responses to injections
579
Count of Units
Unit of Measure: responses to injections
Episodic Regimen Number Analyzed 238 responses to injections [1] 
Excellent or Good
102
  42.9%
Moderate
16
   6.7%
None
2
   0.8%
Response not provided
118
  49.6%
Prophylaxis Regimen Number Analyzed 293 responses to injections [2] 
Excellent or Good
163
  55.6%
Moderate
27
   9.2%
None
14
   4.8%
Response not provided
89
  30.4%
ITI Regimen Number Analyzed 48 responses to injections [3] 
Excellent or Good
20
  41.7%
Moderate
14
  29.2%
None
3
   6.3%
Response not provided
11
  22.9%
[1]
81 participants
[2]
89 participants
[3]
15 participants
5.Secondary Outcome
Title Total Number of Exposure Days (EDs)
Hide Description An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on safety analysis set.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 103
Median (Full Range)
Unit of Measure: days
100.0
(0 to 649)
6.Secondary Outcome
Title Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Hide Description Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Full Range)
Unit of Measure: IU per kilogram per participant per year
Episodic Treatment Number Analyzed 81 participants
197.6
(0 to 3177)
Prophylaxis Treatment Number Analyzed 89 participants
5384.4
(0 to 40126)
ITI Treatment Number Analyzed 15 participants
67310.0
(33323 to 78871)
7.Secondary Outcome
Title Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode
Hide Description Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Full Range)
Unit of Measure: injections
Episodic Treatment Number Analyzed 81 participants
1.0
(1 to 13)
Prophylaxis Treatment Number Analyzed 89 participants
1.0
(1 to 7)
ITI Treatment Number Analyzed 15 participants
1.0
(1 to 22)
8.Secondary Outcome
Title Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode
Hide Description The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Full Range)
Unit of Measure: IU/kg
Episodic Treatment Number Analyzed 81 participants
45.45
(19.2 to 106.0)
Prophylaxis Treatment Number Analyzed 89 participants
48.08
(17.9 to 144.0)
ITI Treatment Number Analyzed 15 participants
189.44
(76.9 to 250.0)
9.Secondary Outcome
Title Change From Baseline in rFVIIIFc Incremental Recovery (IR)
Hide Description Blood samples were taken at trough (predose) 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 FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII 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 and 120
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on FAS participants within the EP. Here number analyzed signifies number of FAS participants with available data for each visit.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 101
Median (Inter-Quartile Range)
Unit of Measure: IU/dL per IU/kg
Change at Week 12 Number Analyzed 35 participants
-0.5
(-1.26 to -0.26)
Change at Week 24 Number Analyzed 34 participants
-0.7
(-1.50 to 0.05)
Change at Week 36 Number Analyzed 39 participants
-0.4
(-1.06 to 0.27)
Change at Week 48 Number Analyzed 37 participants
-0.5
(-1.09 to -0.05)
Change at Week 60 Number Analyzed 25 participants
-0.4
(-1.06 to 0.04)
Change at Week 72 Number Analyzed 21 participants
-0.8
(-1.10 to -0.24)
Change at Week 84 Number Analyzed 15 participants
-0.6
(-1.55 to 0.01)
Change at Week 96 Number Analyzed 7 participants
-0.6
(-1.21 to -0.34)
Change at Week 108 Number Analyzed 2 participants
-1.5
(-2.68 to -0.31)
Change at Week 120 Number Analyzed 1 participants
-0.6
(-0.6 to -0.6)
10.Secondary Outcome
Title Number of Participants With Response to Immune Tolerance Induction (ITI)
Hide Description Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR >=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life >=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on ITI analysis set which was defined as all participants who consented to and initiated the ITI sub-study.
Arm/Group Title Recombinant Coagulation Factor VIII Fc Fusion Protein
Hide Arm/Group Description:
Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Success
5
  33.3%
Partial Success
2
  13.3%
Early Withdrawal
3
  20.0%
ITI Ongoing at end of Study
5
  33.3%
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 AEs are treatment-emergent AEs i.e. AE that was present prior to receiving first injection of rFVIIIFc 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 VIII Fc Fusion Protein
Hide Arm/Group Description Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached >= 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 BU/mL) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
All-Cause Mortality
Recombinant Coagulation Factor VIII Fc Fusion Protein
Affected / at Risk (%)
Total   1/103 (0.97%)    
Hide Serious Adverse Events
Recombinant Coagulation Factor VIII Fc Fusion Protein
Affected / at Risk (%) # Events
Total   60/103 (58.25%)    
Blood and lymphatic system disorders   
Factor viii inhibition  1  28/103 (27.18%)  29
Febrile neutropenia  1  1/103 (0.97%)  1
Spontaneous haematoma  1  1/103 (0.97%)  1
Cardiac disorders   
Supraventricular tachycardia  1  1/103 (0.97%)  1
Gastrointestinal disorders   
Tongue haemorrhage  1  1/103 (0.97%)  1
General disorders   
Device related thrombosis  1  1/103 (0.97%)  1
Pyrexia  1  4/103 (3.88%)  4
Infections and infestations   
Bacterial sepsis  1  1/103 (0.97%)  1
Gastroenteritis norovirus  1  1/103 (0.97%)  1
Haematoma infection  1  1/103 (0.97%)  1
Meningitis aseptic  1  1/103 (0.97%)  1
Parainfluenzae virus infection  1  2/103 (1.94%)  2
Pneumonia  1  2/103 (1.94%)  2
Rotavirus infection  1  1/103 (0.97%)  1
Staphylococcal bacteraemia  1  1/103 (0.97%)  2
Staphylococcal infection  1  2/103 (1.94%)  2
Staphylococcal skin infection  1  1/103 (0.97%)  1
Vascular device infection  1  2/103 (1.94%)  3
Viral infection  1  2/103 (1.94%)  2
Viral upper respiratory tract infection  1  2/103 (1.94%)  2
Injury, poisoning and procedural complications   
Concussion  1  1/103 (0.97%)  4
Contusion  1  1/103 (0.97%)  1
Craniocerebral injury  1  2/103 (1.94%)  2
Facial bones fracture  1  1/103 (0.97%)  1
Fall  1  11/103 (10.68%)  19
Head injury  1  8/103 (7.77%)  13
Palate injury  1  1/103 (0.97%)  1
Post procedural haemorrhage  1  1/103 (0.97%)  1
Skin laceration  1  1/103 (0.97%)  1
Traumatic haematoma  1  1/103 (0.97%)  1
Vascular access site haematoma  1  1/103 (0.97%)  1
Musculoskeletal and connective tissue disorders   
Haemarthrosis  1  2/103 (1.94%)  2
Haematoma muscle  1  1/103 (0.97%)  1
Soft tissue haemorrhage  1  1/103 (0.97%)  1
Nervous system disorders   
Febrile convulsion  1  2/103 (1.94%)  2
Haemorrhage intracranial  1  2/103 (1.94%)  2
Intraventricular haemorrhage  1  1/103 (0.97%)  1
Product Issues   
Device issue  1  1/103 (0.97%)  1
Psychiatric disorders   
Mental status changes  1  1/103 (0.97%)  1
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/103 (0.97%)  1
Surgical and medical procedures   
Arteriovenous fistula operation  1  1/103 (0.97%)  1
Central venous catheter removal  1  1/103 (0.97%)  1
Central venous catheterisation  1  26/103 (25.24%)  30
Ventriculo-peritoneal shunt  1  1/103 (0.97%)  1
Vascular disorders   
Deep vein thrombosis  1  1/103 (0.97%)  1
Haematoma  1  3/103 (2.91%)  3
Poor venous access  1  3/103 (2.91%)  3
Subgaleal haematoma  1  1/103 (0.97%)  1
1
Term from vocabulary, MedDra 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Recombinant Coagulation Factor VIII Fc Fusion Protein
Affected / at Risk (%) # Events
Total   85/103 (82.52%)    
Blood and lymphatic system disorders   
Iron deficiency anaemia  1  10/103 (9.71%)  10
Gastrointestinal disorders   
Constipation  1  9/103 (8.74%)  9
Diarrhoea  1  18/103 (17.48%)  23
Teething  1  12/103 (11.65%)  23
Vomiting  1  19/103 (18.45%)  20
General disorders   
Pyrexia  1  31/103 (30.10%)  47
Infections and infestations   
Conjunctivitis  1  8/103 (7.77%)  8
Ear infection  1  19/103 (18.45%)  28
Gastroenteritis  1  7/103 (6.80%)  7
Hand-foot-and-mouth disease  1  6/103 (5.83%)  6
Influenza  1  10/103 (9.71%)  14
Nasopharyngitis  1  31/103 (30.10%)  54
Otitis media  1  10/103 (9.71%)  11
Rhinitis  1  7/103 (6.80%)  11
Upper respiratory tract infection  1  28/103 (27.18%)  41
Varicella  1  6/103 (5.83%)  6
Viral infection  1  17/103 (16.50%)  32
Viral upper respiratory tract infection  1  11/103 (10.68%)  27
Injury, poisoning and procedural complications   
Contusion  1  9/103 (8.74%)  16
Fall  1  52/103 (50.49%)  146
Head injury  1  28/103 (27.18%)  63
Limb injury  1  8/103 (7.77%)  9
Lip injury  1  6/103 (5.83%)  6
Mouth injury  1  9/103 (8.74%)  10
Skin abrasion  1  7/103 (6.80%)  19
Skin laceration  1  9/103 (8.74%)  13
Vaccination complication  1  6/103 (5.83%)  6
Respiratory, thoracic and mediastinal disorders   
Cough  1  13/103 (12.62%)  20
Rhinorrhoea  1  9/103 (8.74%)  9
Skin and subcutaneous tissue disorders   
Eczema  1  6/103 (5.83%)  9
Rash  1  10/103 (9.71%)  12
1
Term from vocabulary, MedDra 22.0
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Bioverativ, a Sanofi company
Phone: 800-633-1610 ext 6
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi ( Bioverativ, a Sanofi company )
ClinicalTrials.gov Identifier: NCT02234323    
Other Study ID Numbers: 997HA306
2013-005512-10 ( EudraCT Number )
First Submitted: August 29, 2014
First Posted: September 9, 2014
Results First Submitted: July 28, 2020
Results First Posted: August 13, 2020
Last Update Posted: August 13, 2020