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Clinical Trial Results:
An open-label, non-investigational product, multi-center, lead-in study to evaluate prospective efficacy and selected safety data of current factor IX (FIX) or factor VIII (FVIII) prophylaxis replacement therapy in the usual care setting of moderately severe to severe adult hemophilia B participants (FIX:C less than or equal to [<=]2percentage [%]) who are negative for neutralizing antibodies to adeno-associated virus vector-spark100 (BENEGENE-1) and moderately severe to severe hemophilia A adult participants (FVIII:C <=1%) who are negative for neutralizing antibodies to adeno-associated virus vector 6 (AAV6), prior to the respective therapeutic phase 3 gene therapy studies.

Summary
EudraCT number	2017-001271-23
Trial protocol	SE GB IE DE FR ES NL
Global end of trial date	12 Dec 2024

Results information
Results version number	v1(current)
This version publication date	12 Nov 2025
First version publication date	12 Nov 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C0371004

ISRCTN number

US NCT number

NCT03587116

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

66 Hudson Boulevard East, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Apr 2025

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Dec 2024

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to establish prospective efficacy data of FIX or FVIII prophylaxis replacement therapy, in the usual care setting of hemophilia B participants who are negative for neutralizing antibodies (nAb) to adeno-associated virus vector (AAV)-Spark100 or hemophilia A participants who are negative for nAb to AAV6.

Protection of trial subjects

The study was in compliance with the ethical principles derived from international guidelines, including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines; applicable International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines; applicable laws and regulations, including applicable privacy laws.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Jul 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 11

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Brazil: 11

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Greece: 9

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Belgium: 2

Country: Number of subjects enrolled

Saudi Arabia: 11

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

Sweden: 6

Country: Number of subjects enrolled

Korea, Republic of: 7

Country: Number of subjects enrolled

Türkiye: 52

Country: Number of subjects enrolled

Israel: 2

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

United States: 19

Country: Number of subjects enrolled

United Kingdom: 6

Worldwide total number of subjects

212

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

212

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 212 participants were enrolled in this study.

Screening details

Participants with moderately severe to severe adult hemophilia B or hemophilia A who received FIX and FVIII standard prophylaxis replacement therapy in the usual care setting were enrolled in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not applicable

Are arms mutually exclusive

Yes

Standard of Care FIX Replacement Therapy (Hemophilia B)

Arm description

Participants with moderately severe to severe hemophilia B who administered their own current FIX replacement therapy in the usual healthcare setting were included. No investigational product was administered as a part of this study.

Arm type

No investigational product

Investigational medicinal product name

FIX replacement therapy

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Hemophilia B participants remained on their current FIX replacement therapy using their usual prophylaxis regimen.

Standard of Care FVIII Replacement Therapy (Hemophilia A)

Arm description

Participants with moderately severe to severe hemophilia A who administered their own current FVIII replacement therapy in the usual healthcare setting were included. No investigational product was administered as a part of this study.

Arm type

No investigational product

Investigational medicinal product name

FVIII replacement therapy

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Hemophilia A participants remained on their current FVIII replacement therapy using their usual prophylaxis regimen.

Number of subjects in period 1	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Started	111	101
Completed	107	99
Not completed	4	2
Consent withdrawn by subject	4	-
No Longer Met Eligibility Criteria	-	1
Lost to follow-up	-	1

Baseline characteristics

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Reporting group title

Standard of Care FIX Replacement Therapy (Hemophilia B)

Reporting group description

Reporting group title

Standard of Care FVIII Replacement Therapy (Hemophilia A)

Reporting group description

Reporting group values	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)	Total
Number of subjects	111	101	212
Age categorical
Units: Subjects
In Utero	0	0	0
Preterm newborn infants (gestional age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days - 23 months)	0	0	0
Children (2 - 11 years)	0	0	0
12 - 17 years	0	0	0
Adults (18 - 64 years)	111	101	212
From 65 - 84 years	0	0	0
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	32.5 ( 11.25 )	31.8 ( 11.21 )	-
Gender categorical
Units: Subjects
Male	111	101	212
Female	0	0	0
Race
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	18	17	35
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	2	6	8
White	90	78	168
More than one race	1	0	1
Unknown or Not Reported	0	0	0
Ethnicity
Units: Subjects
Hispanic or Latino	4	4	8
Not Hispanic or Latino	91	76	167
Unknown or Not Reported	16	21	37

End points

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Reporting group title

Standard of Care FIX Replacement Therapy (Hemophilia B)

Reporting group description

Reporting group title

Standard of Care FVIII Replacement Therapy (Hemophilia A)

Reporting group description

Primary: Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

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End point title

Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set ^[1] ^[2]

End point description

ABR per participant calculated as number of bleeds over number of days from baseline visit (Day 1 of study) to end of study*365.25 days. All bleeds=treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an informed consent form (ICF), had their blood sample collected and assayed for bioengineered AAV capsid, derived from a naturally occurring AAV serotype (AAV-Spark100) or adeno-associated virus 6(AAV6) immunity testing, who were subsequently identified as nAb negative(negative for nAb to AAV-Spark100 for hemophilia B cohort), met inclusion/exclusion criteria and who participated in prospective data collection phase as part of their usual healthcare setting.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	110
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	3.61 ( 7.634 )
All bleeds	4.46 ( 9.446 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set ^[3] ^[4]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study *365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for hemophilia B cohort), met inclusion/ exclusion criteria and who participated and completed at least 6 months of prospective data collection phase as part of their usual healthcare setting.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	107
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	3.71 ( 7.717 )
All bleeds	4.56 ( 9.557 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[5] ^[6]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during prospective data collection period in hemophilia B participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	39
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	4.21 ( 10.609 )
All bleeds	4.78 ( 10.887 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[7] ^[8]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during retrospective data collection period in hemophilia B participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected. Here, “Subjects Analyzed” signifies number of participants evaluable for this outcome measure.

End point type

Primary

End point timeframe

During retrospective data collection period (12 months before screening collected in the hemophilia history case report form [CRF])

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	38
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	5.42 ( 8.163 )
All bleeds	6.79 ( 10.390 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[9] ^[10]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during retrospective and prospective data collection period in hemophilia B participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected. Here, "Subjects Analyzed” signifies number of participants evaluable for this outcome measure.

End point type

Primary

End point timeframe

From start of retrospective data collection period (12 months before screening collected in hemophilia history CRF) up to end of prospective data collection follow-up of period (maximum follow-up:1269 days), for a total of approximately 4.5 years

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	38
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	4.65 ( 7.589 )
All bleeds	5.48 ( 8.284 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set ^[11] ^[12]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds=treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated in the prospective data collection phase as part of their usual healthcare setting.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	96
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	4.87 ( 7.246 )
All bleeds	6.10 ( 10.578 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set ^[13] ^[14]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated and completed at least 6 months of the prospective data collection phase as part of their usual healthcare setting.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	81
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	3.82 ( 5.665 )
All bleeds	4.33 ( 6.700 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[15] ^[16]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during prospective data collection period in hemophilia A participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Primary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	7.62 ( 9.907 )
All bleeds	10.86 ( 16.692 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[17] ^[18]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during retrospective data collection period in hemophilia A participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Primary

End point timeframe

During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	9.83 ( 13.656 )
All bleeds	14.29 ( 18.208 )

No statistical analyses for this end point

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

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End point title

ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[19] ^[20]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. All bleeds included treated and untreated bleeds. A treated bleed was defined as an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure, ABR for all and treated bleeds during retrospective and prospective data collection period in hemophilia A participants per protocol amendment 5 analysis set was reported. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Primary

End point timeframe

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	9.01 ( 11.908 )
All bleeds	12.77 ( 16.290 )

No statistical analyses for this end point

Secondary: Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

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End point title

Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set ^[21]

End point description

AIR per participant was calculated as the number of infusions received over number of days from baseline visit (Day 1) to end of study * 365.25 days. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for the hemophilia B cohort), met the inclusion/ exclusion criteria and who participated in the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	110
Units: Infusions per year
arithmetic mean (standard deviation)	62.81 ( 33.250 )

No statistical analyses for this end point

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

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End point title

AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set ^[22]

End point description

AIR per participant was calculated as the number of infusions received over number of days from baseline visit (Day 1) to end of study * 365.25 days. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for the hemophilia B cohort), met the inclusion/ exclusion criteria and who participated and completed at least 6 months of the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	107
Units: Infusions per year
arithmetic mean (standard deviation)	62.82 ( 33.213 )

No statistical analyses for this end point

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[23]

End point description

AIR per participant was calculated as the number of infusions received over number of days from baseline visit (Day 1) to end of study * 365.25 days. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	39
Units: Infusions per year
arithmetic mean (standard deviation)	56.97 ( 20.987 )

No statistical analyses for this end point

Secondary: AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[24]

End point description

End point type

Secondary

End point timeframe

During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	39
Units: Infusions per year
arithmetic mean (standard deviation)	66.97 ( 30.535 )

No statistical analyses for this end point

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

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End point title

AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[25]

End point description

AIR combining retrospective and prospective data was calculated as (number of infusions from baseline visit (Day 1) to end of study + number of infusions collected in the Hemophilia History form) / (number of days from baseline visit (Day 1) to end of study + 365.25) / 365.25. Protocol Amendment 5 analysis set included all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

End point type

Secondary

End point timeframe

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	39
Units: Infusions per year
arithmetic mean (standard deviation)	60.98 ( 23.130 )

No statistical analyses for this end point

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

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End point title

AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set ^[26]

End point description

AIR per participant was calculated as the number of infusions received over number of days from baseline visit (Day 1) to end of study * 365.25 days. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated in the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	96
Units: Infusions per year
arithmetic mean (standard deviation)	127.07 ( 51.784 )

No statistical analyses for this end point

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

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End point title

AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set ^[27]

End point description

AIR per participant was calculated as the number of infusions received over number of days from baseline visit (Day 1) to end of study * 365.25 days. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated and completed at least 6 months of the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	81
Units: Infusions per year
arithmetic mean (standard deviation)	127.12 ( 55.418 )

No statistical analyses for this end point

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

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End point title

AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[28]

End point description

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Infusions per year
arithmetic mean (standard deviation)	133.19 ( 56.725 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

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End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set ^[29]

End point description

Annualized factor consumption was calculated as the total factor replacement therapy consumption (in international unit [IU] and dose) *365.25 days/number of days during the observation time period while the participant received factor prophylaxis replacement therapy in the usual care setting from baseline visit (Day 1) to end of study. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for the hemophilia B cohort), met the inclusion/ exclusion criteria and who participated in the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	110
Units: International units per year
arithmetic mean (standard deviation)	238312 ( 127817 )

No statistical analyses for this end point

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

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End point title

AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[30]

End point description

End point type

Secondary

End point timeframe

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Infusions per year
arithmetic mean (standard deviation)	139.88 ( 52.490 )

No statistical analyses for this end point

Secondary: AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Top of page

End point title

AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[31]

End point description

End point type

Secondary

End point timeframe

During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: Infusions per year
arithmetic mean (standard deviation)	141.88 ( 50.487 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

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End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set ^[32]

End point description

Annualized factor consumption was calculated as the total factor replacement therapy consumption (in IU and dose) *365.25 days/number of days during the observation time period while the participant received factor prophylaxis replacement therapy in the usual care setting from baseline visit (Day 1) to end of study. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for the hemophilia B cohort), met the inclusion/ exclusion criteria and who participated and completed at least 6 months of the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	107
Units: International units per year
arithmetic mean (standard deviation)	240501 ( 128676 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Top of page

End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set ^[33]

End point description

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	39
Units: International units per year
arithmetic mean (standard deviation)	223408 ( 85995 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Top of page

End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set ^[34]

End point description

Annualized factor consumption was calculated as the total factor replacement therapy consumption (in IU and dose) *365.25 days/number of days during the observation time period while the participant received factor prophylaxis replacement therapy in the usual care setting from baseline visit (Day 1) to end of study. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated in the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	96
Units: International units per year
arithmetic mean (standard deviation)	304998 ( 153932 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Top of page

End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set ^[35]

End point description

Annualized factor consumption was calculated as the total factor replacement therapy consumption (in IU and dose) *365.25 days/number of days during the observation time period while the participant received factor prophylaxis replacement therapy in the usual care setting from baseline visit (Day 1) to end of study. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for the hemophilia A cohort), met the inclusion/ exclusion criteria and who participated and completed at least 6 months of the prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	81
Units: International units per year
arithmetic mean (standard deviation)	314195 ( 163786 )

No statistical analyses for this end point

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Top of page

End point title

Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set ^[36]

End point description

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	24
Units: International units per year
arithmetic mean (standard deviation)	235097 ( 67977 )

No statistical analyses for this end point

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

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End point title

ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set ^[37]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25 days. Spontaneous bleeds: bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. All bleeds included treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for hemophilia B cohort), met inclusion/ exclusion criteria and who participated in prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	110
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	2.11 ( 3.835 )
All bleeds	2.79 ( 6.411 )

No statistical analyses for this end point

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Top of page

End point title

ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set ^[38]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1 of the study) to end of study*365.25 days. Traumatic bleeds were defined as bleeding event occurring for an apparent or known reason. All bleeds included treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV-Spark100 for hemophilia B cohort), met inclusion/exclusion criteria and who participated in prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	110
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	1.50 ( 6.380 )
All bleeds	1.68 ( 6.623 )

No statistical analyses for this end point

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Top of page

End point title

ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set ^[39]

End point description

ABR per participant calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25days. Spontaneous bleeds: bleeding for no apparent or known reason particularly into joints, muscles, soft tissues. All bleeds=treated and untreated bleeds. Treated bleed:event necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Untreated bleed:event not necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Per-Protocol analysis set: all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative(negative for nAb to AAV-Spark100 for hemophilia B cohort),met inclusion/exclusion criteria and who participated and completed at least 6 months of prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	107
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	2.17 ( 3.872 )
All bleeds	2.84 ( 6.490 )

No statistical analyses for this end point

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Top of page

End point title

ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set ^[40]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25 days. Traumatic bleeds were defined as bleeding event occurring for an apparent or known reason. All bleeds=treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative(negative for nAb to AAV-Spark100 for hemophilia B cohort),met inclusion/exclusion criteria and who participated and completed at least 6 months of prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)
Number of subjects analysed	107
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	1.54 ( 6.465 )
All bleeds	1.72 ( 6.710 )

No statistical analyses for this end point

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Top of page

End point title

ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set ^[41]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25 days. Spontaneous bleeds: bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. All bleeds included treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for hemophilia A cohort), met inclusion/ exclusion criteria and who participated in prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	96
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	3.15 ( 5.948 )
All bleeds	3.89 ( 7.552 )

No statistical analyses for this end point

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Top of page

End point title

ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set ^[42]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25 days. Traumatic bleeds were defined as bleeding event occurring for an apparent or known reason. All bleeds included treated and untreated bleeds. A treated bleed: event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. An untreated bleed was defined as an event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Efficacy analysis set included participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for hemophilia A cohort), met inclusion/exclusion criteria and who participated in prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	96
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	1.78 ( 3.893 )
All bleeds	2.27 ( 5.503 )

No statistical analyses for this end point

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Top of page

End point title

ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set ^[43]

End point description

ABR per participant calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25days. Spontaneous bleeds: bleeding for no apparent or known reason particularly into joints,muscles, soft tissues. All bleeds=treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72hours of signs or symptoms of bleeding. Per-Protocol analysis set: all participants who signed an ICF,had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing,who were subsequently identified as nAb negative(negative for nAb to AAV6 for hemophilia A cohort),met inclusion/exclusion criteria and who participated and completed at least 6 months of prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	81
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	2.37 ( 4.101 )
All bleeds	2.73 ( 5.143 )

No statistical analyses for this end point

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Top of page

End point title

ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set ^[44]

End point description

ABR per participant was calculated as number of bleeds over number of days from baseline visit (Day 1) to end of study*365.25 days. Traumatic bleeds were defined as bleeding event occurring for an apparent or known reason. All bleeds=treated and untreated bleeds. Treated bleed: event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Per-Protocol analysis set included all participants who signed an ICF, had their blood sample collected and assayed for AAV-Spark100 or AAV6 immunity testing, who were subsequently identified as nAb negative (negative for nAb to AAV6 for hemophilia A cohort), met inclusion/exclusion criteria and who participated and completed at least 6 months of prospective data collection phase as part of their usual healthcare setting.

End point type

Secondary

End point timeframe

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 948 days])

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	81
Units: Bleeds per year
arithmetic mean (standard deviation)
Treated bleeds	1.45 ( 3.467 )
All bleeds	1.60 ( 3.608 )

No statistical analyses for this end point

Other pre-specified: Number of Participants With Serious Adverse Events (SAEs)

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End point title

Number of Participants With Serious Adverse Events (SAEs)

End point description

An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE was any untoward medical occurrence at any dose that met 1 of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; other important medical events per protocol of the study. Safety analysis set (SAS) included all enrolled participants (negative for nAb to AAV-Spark100 for the hemophilia B cohort, or negative for nAb to AAV6 for the hemophilia A cohort) who entered the prospective data collection phase.

End point type

Other pre-specified

End point timeframe

During prospective data collection period: Day 1 through end of study visit (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	111	101
Units: Participants	9	4

No statistical analyses for this end point

Other pre-specified: Number of Participants With Adverse Events of Special Interest (AESIs)

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End point title

Number of Participants With Adverse Events of Special Interest (AESIs)

End point description

An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Adverse events of special interest were FIX/FVIII inhibitor development, thrombotic events, and FIX hypersensitivity events for this study. SAS included all enrolled participants (negative for nAb to AAV-Spark100 for the hemophilia B cohort, or negative for nAb to AAV6 for the hemophilia A cohort) who entered the prospective data collection phase.

End point type

Other pre-specified

End point timeframe

During prospective data collection period: Day 1 through end of study visit (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

End point values	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Number of subjects analysed	111	101
Units: Participants	2	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

During prospective data collection period (from baseline visit of the study [Day 1] up to end of study follow-up [maximum follow-up: 1269 days])

Adverse event reporting additional description

Same event may occur as both non-SAE and SAE but are distinct events. An event may be categorised as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety analysis set was evaluated.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

27.1

Reporting group title

Standard of Care FIX Replacement Therapy (Hemophilia B)

Reporting group description

Reporting group title

Standard of Care FVIII Replacement Therapy (Hemophilia A)

Reporting group description

Serious adverse events	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 111 (8.11%)	4 / 101 (3.96%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	0 / 111 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Joint injury
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament rupture
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament sprain
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth fracture
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Enteritis
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	2 / 111 (1.80%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoidal haemorrhage
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	0 / 111 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	0 / 111 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Haemophilic arthropathy
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arthropathy
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	1 / 111 (0.90%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	0 / 111 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Standard of Care FIX Replacement Therapy (Hemophilia B)	Standard of Care FVIII Replacement Therapy (Hemophilia A)
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 111 (3.60%)	0 / 101 (0.00%)
Vascular disorders
Haematoma
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	2 / 111 (1.80%)	0 / 101 (0.00%)
occurrences all number	2	0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: MedDRA v27.1 was used for Hemophilia B cohort. MedDRA v26.0 was used for Hemophilia A cohort.
subjects affected / exposed	2 / 111 (1.80%)	0 / 101 (0.00%)
occurrences all number	2	0

More information

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Were there any global substantial amendments to the protocol? Yes

27 Jun 2019

Including an additional cohort (hemophilia A population) as part of the 6-month lead-in study, to support the initiation of the hemophilia A gene therapy Phase 3 study. Incorporate administrative changes from the 6 previous protocol administrative change letters (PACLs).

17 May 2022

Clarified that participant with a history of a neoplasm (including hepatic malignancy) that required treatment (e.g., chemotherapy, radiotherapy, immunotherapy), is excluded, except for adequately treated basal or squamous cell carcinoma of the skin or a surgically removed benign neoplasm not requiring chemotherapy, radiotherapy and/or immunotherapy. Any other neoplasm that has been cured by resection should be discussed between the investigator and sponsor. Clarified that participants with conditions associated with increased thromboembolic risk such as known inherited or acquired thrombophilia, or a history of thrombotic events, including venous thromboembolism, should be excluded so that it is not open to investigator discretion.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Primary: Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Primary: ABR for Treated Bleeds and All Bleeds From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Secondary: ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis set

Other pre-specified: Number of Participants With Serious Adverse Events (SAEs)

Other pre-specified: Number of Participants With Serious Adverse Events (SAEs)

Other pre-specified: Number of Participants With Adverse Events of Special Interest (AESIs)