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)

• ClinicalTrials.gov Identifier: NCT03093480
• Recruitment Status: Completed
• First Posted: March 28, 2017
• Results First Posted: July 7, 2021
• Last Update Posted: March 28, 2022
• Sponsor: Bioverativ, a Sanofi company
• Collaborator: Swedish Orphan Biovitrum
• Information provided by (Responsible Party): Sanofi ( Bioverativ, a Sanofi company )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia A With Inhibitors
• Intervention: Biological: rFVIIIFc
• Enrollment: 16

Participant Flow

Recruitment Details	The study was conducted at 14 active centers in 7 countries between 08-Dec-2017 to 16-Feb-2021.
Pre-assignment Details	Total 16 participants were screened, enrolled and received drug.

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description	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.
Period Title: Overall Study
Started [1]	16
Tapering Period [2]	10
Follow-up Period [3]	10
Completed	16
Not Completed	0
[1] Immune Tolerance Induction (ITI) Full Analysis Set (ITIFAS): includes all participants who received at least 1 infusion of rFVIIIFc.; [2] Tapering Period Full Analysis Set (TPFAS): includes participants entering the tapering phase of the study; [3] Follow-Up Period Full Analysis Set: includes all participants entering the follow-up phase in the study.

Baseline Characteristics

Arm/Group Title		Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description		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 Number of Baseline Participants		16
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	16 participants
		3.8 (4.06)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants
	Female	NA [1]
	Male	16 100.0%
		[1] Based on inclusion criteria, only male participants were included
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 12.5%
	White	12 75.0%
	More than one race	0 0.0%
	Unknown or Not Reported	2 12.5%

Outcome Measures

1. Primary Outcome

Title	Time to Tolerization With rFVIIIFc
Description	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.
Time Frame	Up to 48 Weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	10
Median (Inter-Quartile Range); Unit of Measure: weeks
	11.7; (9.8 to 26.2)

2. Secondary Outcome

Title	Number of Participants With Immune Tolerance Induction (ITI) Success
Description	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.
Time Frame	Up to 48 Weeks

Outcome Measure Data

Analysis Population Description

ITI full analysis set

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	16
Measure Type: Count of Participants; Unit of Measure: Participants
	10

3. Secondary Outcome

Title	Number of Participants Who Experienced Relapse
Description	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
Time Frame	Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Outcome Measure Data

Analysis Population Description

Tapering Full analysis set

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	10
Measure Type: Count of Participants; Unit of Measure: Participants
	0

4. Secondary Outcome

Title	Annualized Bleeding Rates During ITI Period
Description	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.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: episodes per participant per year
	6.6 (9.50)

5. Secondary Outcome

Title	Annualized Bleeding Rates After ITI Period
Description	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.
Time Frame	Up to 48 weeks (16 weeks Tapering period and 32 weeks follow-up period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: episodes per participant per year
Tapering period	1.0 (1.27)
Follow-up Period	1.2 (2.91)

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) as a Measure of Safety and Tolerability
Description	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.
Time Frame	Up to 2 Years

Outcome Measure Data

Analysis Population Description

ITI full analysis set

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	16
Measure Type: Count of Participants; Unit of Measure: Participants
at least one TEAE	16 100.0%
at least one TESAE	9 56.3%
Death	0 0.0%
discontinuation of treatment and/or the study due to an AE	0 0.0%

7. Secondary Outcome

Title	Average Number of Days Missed From Work or School Per Month During ITI Period
Description	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.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	3
Mean (Standard Deviation); Unit of Measure: days
	2.3 (1.21)

8. Secondary Outcome

Title	Average Number of Days Missed From Work or School Per Month After ITI Period
Description	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.
Time Frame	Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: days
	0 [1] (NA)

[1]

Standard deviation cannot be calculated with 1 participant

9. Secondary Outcome

Title	Annualized Number of Hospitalization Days During ITI Period
Description	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.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: days
	15.4 (32.24)

10. Secondary Outcome

Title	Annualized Number of Hospitalization Days After ITI Period
Description	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.
Time Frame	Up to 48 weeks (16 weeks Tapering period & 32 weeks Follow-up period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: days
	2.7 (8.53)

11. Secondary Outcome

Title	Adherence to Treatment Regimen Overall Study Period
Description	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.
Time Frame	Up to 2 Years

Outcome Measure Data

Analysis Population Description

ITI full analysis set

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: percentage of doses
	100.8 (7.76)

12. Secondary Outcome

Title	Annualized rFVIIIFc Consumption for Overall Study Period
Description	Annualized rFVIIIFc consumption for a treatment period is the total nominal rFVIIIFc (IU/kg) / length of period in days * 365.25.
Time Frame	Up to 2 Years

Outcome Measure Data

Analysis Population Description

ITI Full analysis set

Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description:	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 Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: international unit (IU)/kilograms (kg)
	42713.4 (20938.08)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 2 years) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	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).
Arm/Group Title	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
Arm/Group Description	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.
All-Cause Mortality
	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
	Affected / at Risk (%)
Total	0/16 (0.00%)
Serious Adverse Events
	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
	Affected / at Risk (%)	# Events
Total	9/16 (56.25%)
General disorders
Complication associated with device † 1	1/16 (6.25%)	1
Injection site haematoma † 1	1/16 (6.25%)	1
Pyrexia † 1	1/16 (6.25%)	1
Infections and infestations
Vascular access site infection † 1	1/16 (6.25%)	1
Vascular device infection † 1	4/16 (25.00%)	10
Viral infection † 1	1/16 (6.25%)	1
Injury, poisoning and procedural complications
Contusion † 1	2/16 (12.50%)	2
Head injury † 1	1/16 (6.25%)	1
Mouth injury † 1	1/16 (6.25%)	1
Post procedural oedema † 1	1/16 (6.25%)	1
Musculoskeletal and connective tissue disorders
Arthropathy † 1	1/16 (6.25%)	1
Haemarthrosis † 1	2/16 (12.50%)	4
Synovitis † 1	1/16 (6.25%)	1
Nervous system disorders
Focal dyscognitive seizures † 1	1/16 (6.25%)	1
Product Issues
Device breakage † 1	1/16 (6.25%)	1
1 Term from vocabulary, MedDra 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Recombinant Coagulation Factor VIII Fc (rFVIIIFc)
	Affected / at Risk (%)	# Events
Total	15/16 (93.75%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	4/16 (25.00%)	5
Lymphocytosis † 1	1/16 (6.25%)	1
Monocytosis † 1	1/16 (6.25%)	1
Neutropenia † 1	2/16 (12.50%)	2
Ear and labyrinth disorders
Ear pain † 1	1/16 (6.25%)	2
Eye disorders
Eye pruritus † 1	1/16 (6.25%)	1
Gastrointestinal disorders
Aphthous ulcer † 1	1/16 (6.25%)	1
Diarrhoea † 1	3/16 (18.75%)	8
Vomiting † 1	3/16 (18.75%)	3
General disorders
Administration site extravasation † 1	1/16 (6.25%)	1
Asthenia † 1	1/16 (6.25%)	1
Catheter site extravasation † 1	1/16 (6.25%)	1
Catheter site haematoma † 1	1/16 (6.25%)	4
Catheter site swelling † 1	1/16 (6.25%)	2
Fatigue † 1	1/16 (6.25%)	1
Injection site pain † 1	1/16 (6.25%)	1
Pyrexia † 1	7/16 (43.75%)	23
Immune system disorders
Drug hypersensitivity † 1	1/16 (6.25%)	1
Food allergy † 1	1/16 (6.25%)	3
Seasonal allergy † 1	2/16 (12.50%)	2
Infections and infestations
Bronchitis † 1	1/16 (6.25%)	1
Conjunctivitis † 1	1/16 (6.25%)	3
Ear infection † 1	2/16 (12.50%)	16
Gastritis viral † 1	1/16 (6.25%)	1
Gastroenteritis viral † 1	1/16 (6.25%)	1
Infectious mononucleosis † 1	1/16 (6.25%)	1
Influenza † 1	1/16 (6.25%)	1
Myringitis † 1	1/16 (6.25%)	1
Nasopharyngitis † 1	5/16 (31.25%)	7
Pharyngitis † 1	1/16 (6.25%)	1
Rhinitis † 1	1/16 (6.25%)	2
Tonsillitis † 1	1/16 (6.25%)	1
Vascular device infection † 1	2/16 (12.50%)	3
Viral upper respiratory tract infection † 1	4/16 (25.00%)	4
Injury, poisoning and procedural complications
Animal bite † 1	1/16 (6.25%)	1
Arthropod sting † 1	1/16 (6.25%)	1
Eye injury † 1	1/16 (6.25%)	1
Face injury † 1	1/16 (6.25%)	2
Fall † 1	1/16 (6.25%)	2
Head injury † 1	1/16 (6.25%)	1
Lip injury † 1	1/16 (6.25%)	1
Mouth injury † 1	2/16 (12.50%)	4
Muscle rupture † 1	1/16 (6.25%)	1
Scratch † 1	1/16 (6.25%)	1
Skin abrasion † 1	1/16 (6.25%)	2
Skin laceration † 1	1/16 (6.25%)	1
Soft tissue injury † 1	1/16 (6.25%)	1
Traumatic haematoma † 1	2/16 (12.50%)	2
Wound dehiscence † 1	1/16 (6.25%)	1
Wrong product administered † 1	1/16 (6.25%)	1
Investigations
Blood alkaline phosphatase increased † 1	1/16 (6.25%)	1
Cardiac murmur † 1	1/16 (6.25%)	1
Serum ferritin decreased † 1	1/16 (6.25%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	1/16 (6.25%)	1
Vitamin d deficiency † 1	1/16 (6.25%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/16 (12.50%)	2
Haemarthrosis † 1	1/16 (6.25%)	1
Joint effusion † 1	1/16 (6.25%)	1
Osteochondrosis † 1	1/16 (6.25%)	1
Synovial disorder † 1	1/16 (6.25%)	2
Synovitis † 1	1/16 (6.25%)	1
Nervous system disorders
Migraine † 1	1/16 (6.25%)	1
Product Issues
Device occlusion † 1	1/16 (6.25%)	1
Renal and urinary disorders
Micturition urgency † 1	1/16 (6.25%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/16 (18.75%)	11
Nasal congestion † 1	1/16 (6.25%)	10
Pharyngeal erythema † 1	3/16 (18.75%)	4
Rhinorrhoea † 1	3/16 (18.75%)	9
Wheezing † 1	1/16 (6.25%)	1
Skin and subcutaneous tissue disorders
Eczema † 1	4/16 (25.00%)	4
Eczema infantile † 1	1/16 (6.25%)	1
Rash macular † 1	1/16 (6.25%)	1
Red man syndrome † 1	1/16 (6.25%)	1
Skin lesion † 1	1/16 (6.25%)	1
Urticaria † 1	2/16 (12.50%)	2
Urticaria contact † 1	1/16 (6.25%)	1
1 Term from vocabulary, MedDra 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

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

Results Point of Contact

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

• Responsible Party: Sanofi ( Bioverativ, a Sanofi company )
• ClinicalTrials.gov Identifier: NCT03093480
• Other Study ID Numbers: LPS16473; 2017-000373-36 ( EudraCT Number ); 997HA402 ( Other Identifier: Bioverativ Therapeutics Inc. )
• First Submitted: March 10, 2017
• First Posted: March 28, 2017
• Results First Submitted: May 3, 2021
• Results First Posted: July 7, 2021
• Last Update Posted: March 28, 2022