Hemophilia A, Hemophilia B
Conditions
Brief summary
To establish baseline prospective efficacy data of current FIX prophylaxis replacement therapy in the usual care setting of hemophilia B subjects, who are negative for nAb to AAV-Spark100, prior to the Phase 3 gene therapy study. To establish baseline prospective efficacy data of current FVIII prophylaxis replacement therapy in the usual care setting of hemophilia A subjects, who are negative for nAb to AAV6, prior to the Phase 3 gene therapy study. The enrollment for hemophilia A participants is completed. At this time participants are only being enrolled for hemophilia B cohort.
Detailed description
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 SUBJECTS (FIX:C≤2%) WHO ARE NEGATIVE FOR NEUTRALIZING ANTIBODIES TO ADENO-ASSOCIATED VIRUS VECTOR-SPARK100 (BENEGENE-1) AND MODERATELY SEVERE TO SEVERE HEMOPHILIA A ADULT SUBJECTS (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
Interventions
DRUGStandard of Care FIX Replacement therapy
There is no investigational product being administered. Subjects will be administering their own standard of care FIX replacement therapy.
There is no investigational product being administered. Subjects will be administering their own standard of care FVIII replacement therapy.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
The data obtained from this lead-in study will serve as the control group for the subsequent Phase 3 gene therapy study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Hemophilia B Population: 1. Evidence of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study. 2. Willing and able to comply with scheduled visits, FIX prophylaxis treatment plan, laboratory tests and other study procedures. 3. Males ≥ 18 and \<65 years of age with moderately severe to severe hemophilia B and documented FIX activity (≤2%) prior to baseline visit. 4. Previous experience with FIX therapy (≥50 documented exposure days to a FIX protein product such as recombinant, plasma-derived or extended half-life FIX product). 5. Participants on FIX prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FIX product) must have the intention to remain on FIX prophylaxis replacement therapy for the duration of the study. 6. No known hypersensitivity to FIX replacement product. 7. No history of FIX inhibitor (clinical or laboratory-based assessment) defined as a titer * 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FIX administration. Participants will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study. Hemophilia A Population: 1. Evidence of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study. 2. Willing and able to comply with scheduled visits, FVIII prophylaxis treatment plan, laboratory tests and other study procedures. 3. Males ≥18 and \<65 years of age with moderately severe to severe hemophilia A and documented FVIII activity (≤1%) prior to baseline visit. 4. Previous experience with FVIII therapy (≥150 documented exposure days to a FVIII protein product such as recombinant, plasma-derived or extended half-life FVIII product). 5. Participants must be on a stable FVIII prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FVIII product) at study entry and must have the intention to remain on FVIII prophylaxis replacement therapy for the duration of the study. This does not include nonfactor treatments, which are prohibited. 6. No known hypersensitivity to FVIII replacement product. 7. No history of FVIII inhibitor (clinical or laboratory-based assessment) defined as a titer ≥0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FVIII administration. Participants will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study.
Exclusion criteria
1. Anti-AAV-Spark100 neutralizing antibody titer above the established threshold performed by a central laboratory during screening in hemophilia B subjects or Anti-AAV6 neutralizing antibody titer above the established threshold performed by a central laboratory during screening in hemophilia A subjects. 2. Lack of participant compliance with documentation of bleeds and/or prophylaxis replacement therapy administration. 3. If there is no documentation regarding hepatitis status, as defined below, within the last 12 months prior to screening for hepatitis B and 6 months prior to screening for hepatitis C, then participants will be required to have the following hepatitis testing performed at screening: 1. Hepatitis B screening (acute and chronic): HBsAg (also referred to as Hepatitis B surface antigen), HBV-DNA viral assay (also referred to as a nucleic acid test for Hepatitis B virus DNA), and Anti-HBc (also referred to as Total Hepatitis B core antibody). * A participant is not eligible if either HbsAg is positive or HBV-DNA is positive/detectable. * Anti-HBc must be obtained in all participants for determination of whether the participant had prior hepatitis B. If the anti-HBc is positive and both HBsAg and HBV DNA are negative this would be consistent with a prior infection and the subject would be eligible for the study. Anti-HBc must be obtained in all subjects to discriminate between those with no prior hepatitis B and those with prior infection in the event of reactivation. FDA has noted reactivation of hepatitis B virus exists. * One documented negative HBV-DNA viral load is sufficient to assess eligibility. A participant who is currently undergoing anti-viral therapy for hepatitis B is not eligible. 2. Hepatitis C (acute or chronic): * A participant who is currently undergoing anti-viral therapy for chronic hepatitis C is not eligible. * Participants treated with anti-viral therapy for chronic hepatitis C, must have completed anti-viral therapy at least 6 months prior to screening and have a negative HCV-RNA at least 6 months prior to screening. * All participants (who are not currently undergoing anti-viral therapy for chronic hepatitis C) must have a single HCV-RNA load assay (also referred to as a nucleic acid test \[NAT\] for HCV RNA) obtained during the 6 months preceding screening. This includes participants with prior known chronic hepatitis C who have completed treatment with anti-viral therapy. * A participant is not eligible if his HCV-RNA load assay result is positive/detectable. 4. Currently on antiviral therapy for hepatitis B or C. 5. Significant liver disease, as defined by pre-existing diagnosis of portal hypertension, splenomegaly, or hepatic encephalopathy. All participants who do not have the listed pre existing diagnoses above must have the following assessments performed within the last 12 months prior to screening and if not will need to be tested for liver fibrosis status at screening: a serum albumin level below normal limits and/or significant liver fibrosis by any of the following diagnostic modalities: FibroScan median stiffness score \>8 kPa units OR FibroTest/FibroSURE \>0.48\*. \* NOTE: If there is concern regarding the validity of any of the liver fibrosis test results please contact the medical monitor to discuss whether any additional testing needs to be performed (ie, either repeating any test or performing another fibrosis test). Also, note, if a participant has a known history of Gilbert's syndrome, a FibroTest cannot be used for fibrosis testing. 6. Documented serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 within the last 12 months prior to screening. Participants who are HIV positive and stable, have an adequate CD4 count (\>200/mm3) and undetectable viral load (\<50 gc/mL) documented within the preceding 12 months, and are on an antiretroviral drug regimen are eligible to enroll. Participants who have not been tested within the prior 12 months of screening will need to be tested for HIV status at screening. 7. History of chronic infection or other chronic disease that the investigator deems an unacceptable risk. In addition, any participant with conditions associated with increased thromboembolic risk such as known inherited or acquired thrombophilia, or a history of thrombotic events including but not limited to stroke, myocardial infarction, and/or venous thromboembolism, is excluded. 8. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation or other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. In addition, any participant with a history of a neoplasm (including hepatic malignancy) that required treatment (eg, 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. 9. Participation in other studies if involving administration of investigational product(s) within the last 3 months prior to study entry and/or during study participation or in a previous gene therapy clinical study within the last 12 months prior to screening. • Participants already enrolled in this lead-in study (C0371004) may be allowed to participate in the screening and baseline periods of either C0371002 or C3731003 protocols prior to their completion of the end of study visit in this lead-in study. 10. Any participant who previously received fidanacogene elaparvovec (hemophilia B) or giroctocogene fitelparvovec (hemophilia A) or any AAV gene-based therapy. 11. Participants using restricted therapies. 12. Any participant with a planned surgical procedure requiring FIX (hemophilia B) or FVIII (hemophilia A) surgical prophylactic factor treatment in the next 24 months. 13. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study. NOTE: The sponsor's medical team should be contacted if there are any questions regarding any of the inclusion or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | During retrospective data collection period (12 months before screening collected in the hemophilia history CRF) | 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. |
| 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 | 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:948 days), for a total of approximately 3.6 years | 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. |
| Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 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]) | 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. |
| ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
| ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | During retrospective data collection period (12 months before screening collected in the hemophilia history case report form [CRF]) | 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. |
| 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 | 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 | 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. |
| ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 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]) | 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. |
| ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 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:948 days), for a total of approximately 3.6 years | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 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]) | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 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]) | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 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]) | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 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]) | 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. |
| Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
| ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 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]) | 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. |
| ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 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]) | 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. |
| ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 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]) | 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. |
| ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 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]) | 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. |
| ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 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]) | 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. |
| Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 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]) | 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. |
| AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 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]) | 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. |
| AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
| AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | During retrospective data collection period (12 months before screening collected in the hemophilia history CRF) | 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. |
| AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 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 | 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. |
| AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 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]) | 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. |
| AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 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]) | 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. |
| AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 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]) | 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. |
| AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | During retrospective data collection period (12 months before screening collected in the hemophilia history CRF) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | 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]) | 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. |
| Number of Participants With Adverse Events of Special Interest (AESIs) | 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]) | 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. |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Greece, Israel, Italy, Japan, Saudi Arabia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) 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. | 111 |
| Standard of Care FVIII Replacement Therapy (Hemophilia A) 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. | 101 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | No Longer Met Eligibility Criteria | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Standard of Care FIX Replacement Therapy (Hemophilia B) | Standard of Care FVIII Replacement Therapy (Hemophilia A) | Total |
|---|---|---|---|
| Age, Customized 18-44 Years | 93 Participants | 84 Participants | 177 Participants |
| Age, Customized 45-64 Years | 18 Participants | 17 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants | 76 Participants | 167 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 21 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 17 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 78 Participants | 168 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 111 Participants | 101 Participants | 212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 111 | 0 / 101 |
| other Total, other adverse events | 4 / 111 | 0 / 101 |
| serious Total, serious adverse events | 9 / 111 | 4 / 101 |
Outcome results
Primary
ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | Treated bleeds | 4.87 Bleeds per year | Standard Deviation 7.246 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | All bleeds | 6.10 Bleeds per year | Standard Deviation 10.578 |
Primary
ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | Treated bleeds | 3.82 Bleeds per year | Standard Deviation 5.665 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | All bleeds | 4.33 Bleeds per year | Standard Deviation 6.7 |
Primary
ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | Treated bleeds | 7.62 Bleeds per year | Standard Deviation 9.907 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | All bleeds | 10.86 Bleeds per year | Standard Deviation 16.692 |
Primary
ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | Treated bleeds | 3.71 Bleeds per year | Standard Deviation 7.717 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | All bleeds | 4.56 Bleeds per year | Standard Deviation 9.557 |
Primary
ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | Treated bleeds | 4.21 Bleeds per year | Standard Deviation 10.609 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | All bleeds | 4.78 Bleeds per year | Standard Deviation 10.887 |
Primary
ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | Treated bleeds | 9.83 Bleeds per year | Standard Deviation 13.656 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | All bleeds | 14.29 Bleeds per year | Standard Deviation 18.208 |
Primary
ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: During retrospective data collection period (12 months before screening collected in the hemophilia history case report form [CRF])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | Treated bleeds | 5.42 Bleeds per year | Standard Deviation 8.163 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Treated Bleeds and All Bleeds During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | All bleeds | 6.79 Bleeds per year | Standard Deviation 10.39 |
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
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.
Time frame: 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:948 days), for a total of approximately 3.6 years
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | 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 | Treated bleeds | 9.01 Bleeds per year | Standard Deviation 11.908 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | 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 | All bleeds | 12.77 Bleeds per year | Standard Deviation 16.29 |
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
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | 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 | All bleeds | 5.48 Bleeds per year | Standard Deviation 8.284 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | 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 | Treated bleeds | 4.65 Bleeds per year | Standard Deviation 7.589 |
Primary
Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | Treated bleeds | 3.61 Bleeds per year | Standard Deviation 7.634 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | All bleeds | 4.46 Bleeds per year | Standard Deviation 9.446 |
Secondary
ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | Treated bleeds | 3.15 Bleeds per year | Standard Deviation 5.948 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | All bleeds | 3.89 Bleeds per year | Standard Deviation 7.552 |
Secondary
ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | Treated bleeds | 2.37 Bleeds per year | Standard Deviation 4.101 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | All bleeds | 2.73 Bleeds per year | Standard Deviation 5.143 |
Secondary
ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | All bleeds | 2.79 Bleeds per year | Standard Deviation 6.411 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | Treated bleeds | 2.11 Bleeds per year | Standard Deviation 3.835 |
Secondary
ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | Treated bleeds | 2.17 Bleeds per year | Standard Deviation 3.872 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Spontaneous Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | All bleeds | 2.84 Bleeds per year | Standard Deviation 6.49 |
Secondary
ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | Treated bleeds | 1.78 Bleeds per year | Standard Deviation 3.893 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | All bleeds | 2.27 Bleeds per year | Standard Deviation 5.503 |
Secondary
ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | Treated bleeds | 1.45 Bleeds per year | Standard Deviation 3.467 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | All bleeds | 1.60 Bleeds per year | Standard Deviation 3.608 |
Secondary
ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | Treated bleeds | 1.50 Bleeds per year | Standard Deviation 6.38 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | All bleeds | 1.68 Bleeds per year | Standard Deviation 6.623 |
Secondary
ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | Treated bleeds | 1.54 Bleeds per year | Standard Deviation 6.465 |
| Standard of Care FIX Replacement Therapy (Hemophilia B) | ABR for Traumatic Treated Bleeds and All Bleeds During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | All bleeds | 1.72 Bleeds per year | Standard Deviation 6.71 |
Secondary
AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 127.07 Infusions per year | Standard Deviation 51.784 |
Secondary
AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 127.12 Infusions per year | Standard Deviation 55.418 |
Secondary
AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 133.19 Infusions per year | Standard Deviation 56.725 |
Secondary
AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 62.82 Infusions per year | Standard Deviation 33.213 |
Secondary
AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 56.97 Infusions per year | Standard Deviation 20.987 |
Secondary
AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Retrospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 141.88 Infusions per year | Standard Deviation 50.487 |
Secondary
AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: During retrospective data collection period (12 months before screening collected in the hemophilia history CRF)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR During Retrospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 66.97 Infusions per year | Standard Deviation 30.535 |
Secondary
AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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:948 days), for a total of approximately 3.6 years
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 139.88 Infusions per year | Standard Deviation 52.49 |
Secondary
AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | AIR From the Combined Retrospective and Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 60.98 Infusions per year | Standard Deviation 23.13 |
Secondary
Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Infusion Rate (AIR) During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 62.81 Infusions per year | Standard Deviation 33.25 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Efficacy Analysis Set | 304998 International units per year | Standard Deviation 153932 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Per-protocol Analysis Set | 314195 International units per year | Standard Deviation 163786 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia A Participants: Protocol Amendment 5 Analysis Set | 235097 International units per year | Standard Deviation 67977 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Efficacy Analysis Set | 238312 International units per year | Standard Deviation 127817 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Per-protocol Analysis Set | 240501 International units per year | Standard Deviation 128676 |
Secondary
Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Annualized Total Factor IX Replacement Therapy Consumption During Prospective Data Collection Period in Hemophilia B Participants: Protocol Amendment 5 Analysis Set | 223408 International units per year | Standard Deviation 85995 |
Other Pre-specified
Number of Participants With Adverse Events of Special Interest (AESIs)
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Number of Participants With Adverse Events of Special Interest (AESIs) | 2 Participants |
| Standard of Care FVIII Replacement Therapy (Hemophilia A) | Number of Participants With Adverse Events of Special Interest (AESIs) | 0 Participants |
Other Pre-specified
Number of Participants With Serious Adverse Events (SAEs)
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.
Time frame: 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])
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care FIX Replacement Therapy (Hemophilia B) | Number of Participants With Serious Adverse Events (SAEs) | 9 Participants |
| Standard of Care FVIII Replacement Therapy (Hemophilia A) | Number of Participants With Serious Adverse Events (SAEs) | 4 Participants |