Trial Outcomes & Findings for A Study to Evaluate Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Participants With Inhibitors Undergoing the First ITI Treatment (verITI-8 Study) (NCT NCT03093480)

Last Updated: 2022-03-28

Results Overview

Time required for participants to achieve immune tolerance induction (ITI) success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (less than \[\<\] 0.6 Bethesda units/milliliter \[mL\] by the Nijmegen-modified Bethesda assay); incremental recovery (IR) greater than or equal to (\>=) 66 percent (%) of the expected IR in 2 consecutive assessments; half-life (t½) \>= 7 hours.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

Up to 48 Weeks

Results posted on

2022-03-28

Participant Flow

The study was conducted at 14 active centers in 7 countries between 08-Dec-2017 to 16-Feb-2021.

Total 16 participants were screened, enrolled and received drug.

Participant milestones

Participant milestones
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Overall Study STARTED	16
Overall Study Tapering Period	10
Overall Study Follow-up Period	10
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate Efficacy of rFVIIIFc for Immune Tolerance Induction (ITI) in Severe Hemophilia A Participants With Inhibitors Undergoing the First ITI Treatment (verITI-8 Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Age, Continuous	3.8 years STANDARD_DEVIATION 4.06 • n=5 Participants
Sex: Female, Male Female	NA Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 48 Weeks

Population: Participants who are in ITI full analysis set (includes all participants receiving at least 1 infusion of rFVIIIFc) and achieved ITI success

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=10 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Time to Tolerization With rFVIIIFc	11.7 weeks Interval 9.8 to 26.2

SECONDARY outcome

Timeframe: Up to 48 Weeks

Population: ITI full analysis set

Number of participants who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: confirmed negative titers consisting of 2 consecutive negative inhibitor assessments within 2 weeks (\<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay); incremental recovery (IR) \>= 66% of the expected IR at 2 consecutive assessments; half-life (t½) \>=7 hours.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Number of Participants With Immune Tolerance Induction (ITI) Success	10 Participants

SECONDARY outcome

Timeframe: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Population: Tapering Full analysis set

Number of Participants with ITI success who reaches the criteria for relapse (defined as confirmed positive inhibitor titer \>= 0.6 BU/mL or abnormal recovery after tolerance is achieved, and t½ less than \[\<\] 7 hours) evaluated during the Tapering or Follow-Up Periods

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=10 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Number of Participants Who Experienced Relapse	0 Participants

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: ITI full analysis set which excludes participants who were observed for less than 90 days during the period

A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, 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. Annualized bleeding rate for a patient during the ITI period is defined as the number of bleeding episodes divided by the length of the ITI period in days\* 365.25.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=13 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Annualized Bleeding Rates During ITI Period	6.6 episodes per participant per year Standard Deviation 9.50

SECONDARY outcome

Timeframe: Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Population: Tapering period full analysis set excluding participants who were observed for less than 90 days in the period.

A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, 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. Annualized bleeding rate for a patient after the ITT period (for tapering and follow-up period) is defined as the number of bleeding episodes divided by the length of the period after the ITI period in days\* 365.25.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=10 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Annualized Bleeding Rates After ITI Period Tapering period	1.0 episodes per participant per year Standard Deviation 1.27
Annualized Bleeding Rates After ITI Period Follow-up Period	1.2 episodes per participant per year Standard Deviation 2.91

SECONDARY outcome

Timeframe: Up to 2 Years

Population: ITI full analysis set

An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability at least one TEAE	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability at least one TESAE	9 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability Death	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability discontinuation of treatment and/or the study due to an AE	0 Participants

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Participants of ITI full analysis set and who attend school or have a job

Average number of days missed from school or work per month for a period (counting in non-missing diary days) is defined as number of the missing school/work days in the period divided by number of days with data entry in the period. Number of days per month missed from school or work is reported for those who attend school or have a job.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=3 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Average Number of Days Missed From Work or School Per Month During ITI Period	2.3 days Standard Deviation 1.21

SECONDARY outcome

Timeframe: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Population: Participants of Tapering full analysis set and who attended school or have a job

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=1 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Average Number of Days Missed From Work or School Per Month After ITI Period	0 days Standard Deviation NA Standard deviation cannot be calculated with 1 participant

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: ITI Full analysis set but excluding patients who were observed for less than 90 days in the period.

Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days \* 365.25.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=13 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Annualized Number of Hospitalization Days During ITI Period	15.4 days Standard Deviation 32.24

SECONDARY outcome

Timeframe: Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Population: Tapering Period Full analysis set but excluding patients who were observed for less than 90 days in the period.

Annualized number of hospitalization days during a period for a patient is defined as the number of hospitalization days divided by the length of the period in days \* 365.25.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=10 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Annualized Number of Hospitalization Days After ITI Period	2.7 days Standard Deviation 8.53

SECONDARY outcome

Timeframe: Up to 2 Years

Population: ITI full analysis set

Adherence to treatment is based on prescribed daily dose for the overall study period which is defined as the percentage of administered doses versus the prescribed doses to a patient for the entire study duration.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Adherence to Treatment Regimen Overall Study Period	100.8 percentage of doses Standard Deviation 7.76

SECONDARY outcome

Timeframe: Up to 2 Years

Population: ITI Full analysis set

Annualized rFVIIIFc consumption for a treatment period is the total nominal rFVIIIFc (IU/kg) / length of period in days \* 365.25.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Annualized rFVIIIFc Consumption for Overall Study Period	42713.4 international unit (IU)/kilograms (kg) Standard Deviation 20938.08

Adverse Events

Recombinant Coagulation Factor VIII Fc (rFVIIIFc)

Serious events: 9 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 participants at risk Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
General disorders Complication associated with device	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Injection site haematoma	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Pyrexia	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Vascular access site infection	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Vascular device infection	25.0% 4/16 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Viral infection	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Contusion	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Head injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Mouth injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Post procedural oedema	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Arthropathy	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Haemarthrosis	12.5% 2/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Synovitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Nervous system disorders Focal dyscognitive seizures	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Product Issues Device breakage	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).

Other adverse events

Other adverse events
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 participants at risk Participants were to receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 48 Weeks in ITI Period. Participants who met the criteria for immune tolerance induction (ITI) success entered the tapering period and received rFVIIIFc at a dose adjusted according to Investigator judgment based on the FVIII activity levels and with the aim of tapering the rFVIIIFc dose to reach a prophylactic dosing regimen within 16 weeks (4 months). Follow-Up was for 32 weeks under an adjusted prophylactic regimen according to Investigator judgment.
Blood and lymphatic system disorders Iron deficiency anaemia	25.0% 4/16 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Blood and lymphatic system disorders Lymphocytosis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Blood and lymphatic system disorders Monocytosis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Blood and lymphatic system disorders Neutropenia	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Ear and labyrinth disorders Ear pain	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Eye disorders Eye pruritus	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Gastrointestinal disorders Aphthous ulcer	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Gastrointestinal disorders Diarrhoea	18.8% 3/16 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Gastrointestinal disorders Vomiting	18.8% 3/16 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Administration site extravasation	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Asthenia	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Catheter site extravasation	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Catheter site haematoma	6.2% 1/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Catheter site swelling	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Fatigue	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Injection site pain	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
General disorders Pyrexia	43.8% 7/16 • Number of events 23 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Immune system disorders Drug hypersensitivity	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Immune system disorders Food allergy	6.2% 1/16 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Immune system disorders Seasonal allergy	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Bronchitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Conjunctivitis	6.2% 1/16 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Ear infection	12.5% 2/16 • Number of events 16 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Gastritis viral	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Gastroenteritis viral	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Infectious mononucleosis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Myringitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Nasopharyngitis	31.2% 5/16 • Number of events 7 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Pharyngitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Rhinitis	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Tonsillitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Vascular device infection	12.5% 2/16 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Infections and infestations Viral upper respiratory tract infection	25.0% 4/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Animal bite	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Arthropod sting	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Eye injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Face injury	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Fall	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Head injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Lip injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Mouth injury	12.5% 2/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Muscle rupture	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Scratch	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Skin abrasion	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Skin laceration	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Soft tissue injury	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Traumatic haematoma	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Wound dehiscence	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Injury, poisoning and procedural complications Wrong product administered	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Investigations Blood alkaline phosphatase increased	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Investigations Cardiac murmur	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Investigations Serum ferritin decreased	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Metabolism and nutrition disorders Decreased appetite	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Metabolism and nutrition disorders Vitamin d deficiency	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Haemarthrosis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Joint effusion	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Osteochondrosis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Synovial disorder	6.2% 1/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Musculoskeletal and connective tissue disorders Synovitis	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Nervous system disorders Migraine	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Product Issues Device occlusion	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Renal and urinary disorders Micturition urgency	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Respiratory, thoracic and mediastinal disorders Cough	18.8% 3/16 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.2% 1/16 • Number of events 10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	18.8% 3/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	18.8% 3/16 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Respiratory, thoracic and mediastinal disorders Wheezing	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Eczema	25.0% 4/16 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Eczema infantile	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Rash macular	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Red man syndrome	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Skin lesion	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Urticaria	12.5% 2/16 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).
Skin and subcutaneous tissue disorders Urticaria contact	6.2% 1/16 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs (TEAEs) i.e. defined as AEs that developed, worsened, or became serious on or after the first administration of rFVIIIFc. Analysis performed on ITI full analysis set (ITIFAS).

Additional Information

Trial Transparency Team

Bioverativ, a Sanofi company

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER