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 multiplication(*)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 efficacy analysis set was reported. Abbreviations used: AAV6 = adeno-associated virus 6; AAV-Spark100 = Bioengineered AAV capsid, derived from a naturally occurring AAV serotype; nAb = neutralizing antibodies.

Efficacy analysis set: participants who signed an informed consent form (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.

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 analysis set was reported.

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 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.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective data collected. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

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 efficacy analysis set was reported.

Efficacy analysis set: 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.

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 analysis set was reported.

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 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.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

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: 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.

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: 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.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

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: 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.

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: 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.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective data collected.

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: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had retrospective and prospective data collected.

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: 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.

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: 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.

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.

Protocol Amendment 5 analysis set: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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: 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.

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: 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.

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.

Protocol Amendment 5 analysis set: all participants enrolled under Protocol Amendment 5 and afterwards, who fulfilled the inclusion/exclusion criteria and had prospective data collected.

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. Spontaneous bleeds were defined as bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. 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 spontaneous all and treated bleeds during prospective data collection period in hemophilia B participants per efficacy analysis set was reported.

Efficacy analysis set: 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.

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. 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 traumatic all and treated bleeds during prospective data collection period in hemophilia B participants per efficacy analysis set was reported.

Efficacy analysis set: 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.

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. Spontaneous bleeds were defined as bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. 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 spontaneous all and treated bleeds during prospective data collection period in hemophilia B participants per protocol analysis set was reported.

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 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.

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. 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 traumatic all and treated bleeds during prospective data collection period in hemophilia B participants per protocol analysis set was reported.

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 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.

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. Spontaneous bleeds were defined as bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. 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 spontaneous all and treated bleeds during prospective data collection period in hemophilia A participants per efficacy analysis set was reported.

Efficacy analysis set: 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.

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. 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 traumatic all and treated bleeds during prospective data collection period in hemophilia A participants per efficacy analysis set was reported.

Efficacy analysis set: 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.

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. Spontaneous bleeds were defined as bleeding for no apparent or known reason particularly into the joints, muscles, and soft tissues. 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 spontaneous all and treated bleeds during prospective data collection period in hemophilia A participants per protocol analysis set was reported.

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 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.

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. 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 traumatic all and treated bleeds during prospective data collection period in hemophilia A participants per protocol analysis set was reported.

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 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.

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 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.

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 are FIX/FVIII inhibitor development, thrombotic events, and FIX hypersensitivity events for this study.

Safety analysis set 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.