Hemophilia A
Conditions
Brief summary
The purpose of the study is to evaluate the safety, tolerability and time-course profile of FVIII activity after dosing with SB-525 (PF-07055480)
Detailed description
The proposed clinical study uses a recombinant adeno-associated virus 2/6 (AAV2/6) vector encoding the cDNA for the B-domain deleted human F8 (hF8). The secreted FVIII has the same amino acid sequence as approved recombinant anti hemophilic factors (Refacto® and Xyntha®). The SB-525 (PF-07055480) vector encodes a liver-specific promotor module and AAV2/6 exhibits liver tropism, thus providing the potential for long-term hepatic production of FVIII in hemophilia A subjects. The constant production of FVIII after a single SB-525 (PF-07055480) administration may provide potential benefit in durable protection against bleeding and the complications thereof without lifelong repetitive IV factor replacement administration.
Interventions
BIOLOGICALSB-525 (PF-07055480)
Single dose of investigational product SB-525 (PF-07055480)
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male ≥18 years of age * Severe hemophilia A (past evidence of circulating FVIII activity of \< 1% normal) * Treated or exposed to FVIII concentrates or cryoprecipitate for at least 150 exposure days * ≥12 bleeding episodes if receiving on-demand therapy over the preceding 12 months * Agree to use double barrier contraceptive until at least 3 consecutive semen samples are negative for AAV 2/6 after SB-525 infusion
Exclusion criteria
* Presence of neutralizing antibodies * Current inhibitor, or history of FVIII inhibitor (except for transient low titer inhibitor detected in childhood) * History of hypersensitivity response to FVIII * History of Hepatitis B or HIV-1/2 infection * History of Hepatitis C, unless viral assays in two samples, collected at least 6 months apart, are negative * Evidence of any bleeding disorder in addition to hemophilia A * Markers of hepatic inflammation or overt or occult cirrhosis * History of chronic renal disease or creatinine ≥ 1.5 mg/dL * Presence of liver mass on magnetic resonance imaging (MRI), or, positive alpha fetoprotein * Presence of \> grade 2 liver fibrosis on elastography for subjects with history of treated Hepatitis C or suspicion of chronic liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 5 (Week 213 Through Week 264) | Year 5 (Week 213 through Week 264) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208) | At Year 4 (Week 208) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported. |
| Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260) | At Year 5 (Week 260) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 1 (Week 9 Through Week 53) | Year 1 (Week 9 through Week 53) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 2 (Week 54 Through Week 108) | Year 2 (Week 54 through Week 108) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 3 (Week 109 Through Week 160) | Year 3 (Week 109 through Week 160) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 4 (Week 161 Through Week 212) | Year 4 (Week 161 through Week 212) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 5 (Week 213 Through Week 264) | Year 5 (Week 213 through Week 264) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 1 (Week 9 Through Week 53) | Year 1 (Week 9 through Week 53) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 2 (Week 54 Through Week 108) | Year 2 (Week 54 through Week 108) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 3 (Week 109 Through Week 160) | Year 3 (Week 109 through Week 160) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 4 (Week 161 Through Week 212) | Year 4 (Week 161 through Week 212) | FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Baseline (1 week prior to infusion) up to 5 years post-infusion (approximately 5 Years) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria as follows: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect and other situations per protocol. AEs included both SAEs and all non-SAEs. |
| Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52) | At Year 1 (Week 52) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported. |
| Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104) | At Year 2 (Week 104) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported. |
| Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156) | At Year 3 (Week 156) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported. |
| Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208) | At Year 4 (Week 208) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported. |
| Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260) | At Year 5 (Week 260) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported. |
| Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52) | At Year 1 (Week 52) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported. |
| Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104) | At Year 2 (Week 104) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported. |
| Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156) | At Year 3 (Week 156) | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Annualized Bleeding Rate (ABR) | Pre-screening period: 12 months prior to screening; Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years) | Total ABR included both treated and untreated bleeding episodes. In this outcome measure total ABR for pre-screening and post-infusion are reported. Pre-screening total ABR was based on the total number of reported bleeding episodes during 12 months prior to screening visit as reported on CRF's Hemophilia A History page. Screening was 2 months before baseline. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after investigational product/ PF-07055480 (IP) infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used. |
| Total ABR by Severity | Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years) | Total ABR include both treated and untreated bleeding episodes. In this outcome measure total ABR by severity for post-infusion period is reported. Severity was categorized as mild, moderate and severe. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after IP infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used. |
| Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion | Peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, semen, stool and urine were analyzed with quantitative real-time polymerase chain reaction (PCR). Participants must achieve 3 consecutive negative results for analysis for each sample. |
| Annualized Infusion Rate (AIR) | Pre-infusion period: 30 days before screening up to pre-infusion (approximately up to 3.23 months); post-infusion period: 3 weeks post-infusion up to up to date of data cut or conclusion date (maximum up to 5 years) | AIR was calculated and reported for pre-infusion and post-infusion. AIR for pre-infusion was calculated as, a) Excluding prophylaxis: number of FVIII replacement infusions for reasons other than prophylaxis prior to IP infusion/ (\[date of IP infusion - date of screening\] + 30)\] \*365.25, or b) number of FVIII replacement infusions for any reason prior to IP infusion/ (\[date of IP infusion - date of screening\] + 30)\] \*365.25. Screening was 2 months before baseline and baseline was approximately 1-week prior to IP infusion. AIR for post- infusion was calculated as: number of FVIII replacement infusions started at 3 weeks after IP infusion up to date of data cut or conclusion date/ number of days in the observation period for the participant in years, where observation period in years = date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. |
| Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60 | EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health on a 5-point scale. Each dimension had 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and visual analogue scale (VAS). Index score was obtained, according to the health state defined by the 5 dimensions scores, from the Crosswalk Index value calculator and table lookup document under the target country population. A health state is defined by the combination of one level from each of the 5 dimensions. For this study, weights under the US population were used to obtain the Index score. Index score ranged between 0-1, where higher score indicates a better health state, and lower score indicate worse health state. Baseline was defined as the latest non-missing value before IP infusion. |
| Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60 | EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions of health on a 5-point scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is assessed with 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and VAS. EQ-5D-5L VAS: Participants were asked to indicate their current health status on a scale of 0 (worst health) to 100 (best imaginable health), higher scores signified better health status. Baseline was defined as the latest non-missing value before IP infusion. |
| Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion | Time to peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Participants must achieve 3 consecutive negative results for analysis for each sample; where negative suggests values under the limit of detection. |
| Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion | Time to undetectable (negative) value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Time to undetectable is defined as the number of days from IP infusion until the first of 3 consecutive specimens under the limit of detection (negative). |
| Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion | Time to last of 3 consecutive negative value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. |
| Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion | Time to last positive value prior to first of 3 consecutive negatives of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR, where positive suggests values above the limit of detection. |
| Number of Participants With Positive FVIII Inhibitor Levels During the Study | Baseline (one week prior to IP infusion) up to 5 years post-infusion | Positive FVIII inhibitor was assessed using central laboratory using Nijmegen method of the Bethesda assay in an individual with no prior history of FVIII inhibitor. Inhibitor assay results \>0.6 Bethesda units (BU) were considered as positive. Positive results at any timepoint were considered, even if subsequent inhibitor assessment was negative. |
Countries
United States
Participant flow
Recruitment details
Participants with severe hemophilia A were enrolled in this study and received single infusion of SB-525/ PF-07055480. Participants were followed up for maximum of 5 years post-infusion.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg Participants received a single intravenous infusion of PF-07055480 9.0\*10\^11 vg/kg on Day 1. | 2 |
| Cohort 2: PF-07055480 2*10^12 vg/kg Participants received a single intravenous infusion of PF-07055480 2.0\*10\^12 vg/kg on Day 1. | 2 |
| Cohort 3: PF-07055480 1*10^13 vg/kg Participants received a single intravenous infusion of PF-07055480 1.0\*10\^13 vg/kg on Day 1. | 2 |
| Cohort 4: PF-07055480 3*10^13 vg/kg Participants received a single intravenous infusion of PF-07055480 3.0\*10\^13 vg/kg on Day 1. | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Participants Terminated at Month 36 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: PF-07055480 9*10^11 vg/kg | Total | Cohort 4: PF-07055480 3*10^13 vg/kg | Cohort 3: PF-07055480 1*10^13 vg/kg | Cohort 2: PF-07055480 2*10^12 vg/kg |
|---|---|---|---|---|---|
| Age, Continuous | 30.50 Years STANDARD_DEVIATION 9.192 | 30 Years STANDARD_DEVIATION 7.937 | 26.80 Years STANDARD_DEVIATION 6.301 | 32.00 Years STANDARD_DEVIATION 1.414 | 35.50 Years STANDARD_DEVIATION 16.263 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 9 Participants | 3 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 2 Participants | 9 Participants | 4 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 11 Participants | 5 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 5 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 2 / 2 | 5 / 5 |
| serious Total, serious adverse events | 0 / 2 | 2 / 2 | 0 / 2 | 1 / 5 |
Outcome results
Primary
Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.
Time frame: At Year 1 (Week 52)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the Statistical Analysis Plan (SAP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52) | 0.90 Percentage of Normal | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52) | 11.90 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52) | 42.60 Percentage of Normal | Standard Deviation 53.473 |
Primary
Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.
Time frame: At Year 2 (Week 104)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104) | 19.30 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104) | 8.25 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104) | 25.44 Percentage of Normal | Standard Deviation 27.532 |
Primary
Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.
Time frame: At Year 3 (Week 156)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156) | 0.90 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156) | 4.40 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156) | 25.46 Percentage of Normal | Standard Deviation 36.998 |
Primary
Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.
Time frame: At Year 4 (Week 208)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208) | 0.90 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208) | 3.20 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208) | 26.55 Percentage of Normal | Standard Deviation 42.489 |
Primary
Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.
Time frame: At Year 5 (Week 260)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260) | 0.90 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260) | 3.30 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260) | 23.55 Percentage of Normal | Standard Deviation 36.27 |
Primary
Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.
Time frame: At Year 1 (Week 52)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52) | 1.75 Percentage of Normal | Standard Deviation 1.202 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52) | 19.90 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52) | 66.37 Percentage of Normal | Standard Deviation 83.793 |
Primary
Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.
Time frame: At Year 2 (Week 104)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104) | 19.00 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104) | 13.95 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104) | 38.86 Percentage of Normal | Standard Deviation 36.738 |
Primary
Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.
Time frame: At Year 3 (Week 156)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156) | 3.30 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156) | 5.70 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156) | 40.52 Percentage of Normal | Standard Deviation 50.231 |
Primary
Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.
Time frame: At Year 4 (Week 208)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208) | 4.80 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208) | 13.80 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208) | 38.78 Percentage of Normal | Standard Deviation 53.79 |
Primary
Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260)
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.
Time frame: At Year 5 (Week 260)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. For Cohort 1, both participants resumed prophylaxis regimen prior to Week 52, and were excluded from analysis as pre-specified in the SAP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: PF-07055480 2*10^12 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260) | 4.00 Percentage of Normal | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260) | 6.10 Percentage of Normal | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260) | 41.00 Percentage of Normal | Standard Deviation 56.749 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 1 (Week 9 Through Week 53)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 1 (Week 9 through Week 53)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the statistical analysis plan (SAP) of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 1 (Week 9 Through Week 53) | 67.89 Percentage of Normal | Standard Deviation 46.585 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 2 (Week 54 Through Week 108)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 2 (Week 54 through Week 108)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 2 (Week 54 Through Week 108) | 40.38 Percentage of Normal | Standard Deviation 41.498 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 3 (Week 109 Through Week 160)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 3 (Week 109 through Week 160)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 3 (Week 109 Through Week 160) | 27.66 Percentage of Normal | Standard Deviation 41.589 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 4 (Week 161 Through Week 212)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 4 (Week 161 through Week 212)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 4 (Week 161 Through Week 212) | 24.31 Percentage of Normal | Standard Deviation 34.64 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 5 (Week 213 Through Week 264)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 5 (Week 213 through Week 264)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 5 (Week 213 Through Week 264) | 24.87 Percentage of Normal | Standard Deviation 39.509 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 1 (Week 9 Through Week 53)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 1 (Week 9 through Week 53)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 1 (Week 9 Through Week 53) | 107.44 Percentage of Normal | Standard Deviation 72.86 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 2 (Week 54 Through Week 108)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 2 (Week 54 through Week 108)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 2 (Week 54 Through Week 108) | 58.55 Percentage of Normal | Standard Deviation 56.752 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 3 (Week 109 Through Week 160)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 3 (Week 109 through Week 160)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 3 (Week 109 Through Week 160) | 43.95 Percentage of Normal | Standard Deviation 57.466 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 4 (Week 161 Through Week 212)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 4 (Week 161 through Week 212)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 4 (Week 161 Through Week 212) | 39.60 Percentage of Normal | Standard Deviation 51.623 |
Primary
Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 5 (Week 213 Through Week 264)
FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.
Time frame: Year 5 (Week 213 through Week 264)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. As pre-specified in planned analysis in the SAP of the study, this outcome measure was to be assessed only in Cohort 4. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 5 (Week 213 Through Week 264) | 38.62 Percentage of Normal | Standard Deviation 51.844 |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria as follows: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect and other situations per protocol. AEs included both SAEs and all non-SAEs.
Time frame: From Baseline (1 week prior to infusion) up to 5 years post-infusion (approximately 5 Years)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 2 Participants |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 Participants |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 2 Participants |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 2 Participants |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 2 Participants |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 Participants |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 5 Participants |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 Participants |
Secondary
Annualized Infusion Rate (AIR)
AIR was calculated and reported for pre-infusion and post-infusion. AIR for pre-infusion was calculated as, a) Excluding prophylaxis: number of FVIII replacement infusions for reasons other than prophylaxis prior to IP infusion/ (\[date of IP infusion - date of screening\] + 30)\] \*365.25, or b) number of FVIII replacement infusions for any reason prior to IP infusion/ (\[date of IP infusion - date of screening\] + 30)\] \*365.25. Screening was 2 months before baseline and baseline was approximately 1-week prior to IP infusion. AIR for post- infusion was calculated as: number of FVIII replacement infusions started at 3 weeks after IP infusion up to date of data cut or conclusion date/ number of days in the observation period for the participant in years, where observation period in years = date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25.
Time frame: Pre-infusion period: 30 days before screening up to pre-infusion (approximately up to 3.23 months); post-infusion period: 3 weeks post-infusion up to up to date of data cut or conclusion date (maximum up to 5 years)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Annualized Infusion Rate (AIR) | Post-infusion AIR | 58.95 Infusions per year | Standard Deviation 73.97 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR (Excluding Prophylaxis) | 0.00 Infusions per year | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR | 100.43 Infusions per year | Standard Deviation 2.74 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Annualized Infusion Rate (AIR) | Post-infusion AIR | 32.79 Infusions per year | Standard Deviation 25.32 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR | 81.15 Infusions per year | Standard Deviation 108.82 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR (Excluding Prophylaxis) | 2.10 Infusions per year | Standard Deviation 2.97 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR (Excluding Prophylaxis) | 0.00 Infusions per year | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR | 87.93 Infusions per year | Standard Deviation 118.73 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Annualized Infusion Rate (AIR) | Post-infusion AIR | 29.03 Infusions per year | Standard Deviation 33.27 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR (Excluding Prophylaxis) | 1.62 Infusions per year | Standard Deviation 2.26 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Annualized Infusion Rate (AIR) | Post-infusion AIR | 3.56 Infusions per year | Standard Deviation 7.55 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Annualized Infusion Rate (AIR) | Pre-infusion AIR | 120.86 Infusions per year | Standard Deviation 30.04 |
Secondary
Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60
EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions of health on a 5-point scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is assessed with 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and VAS. EQ-5D-5L VAS: Participants were asked to indicate their current health status on a scale of 0 (worst health) to 100 (best imaginable health), higher scores signified better health status. Baseline was defined as the latest non-missing value before IP infusion.
Time frame: Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60
Population: Safety population. Here, Number Analyzed =participants evaluable for specified timepoints. Participants from Cohort 1: PF-07055480 9\*10\^11 vg/kg and Cohort 2: PF-07055480 2\*10\^12 vg/kg did not attend the study visit or missed the EQ-5D-5L assessment at Months 24 and 60 and participants from Cohort 3: PF-07055480 1\*10\^13 vg/kg did not attend the study visit or missed the EQ-5D-5L assessment at Month 24; hence, no participants were analyzed for Cohorts 1, 2 and 3 at the mentioned visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 36 | 0.0 Units on a scale | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 52 | -1.0 Units on a scale | Standard Deviation 12.73 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 12 | 4.5 Units on a scale | Standard Deviation 6.36 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Baseline | 75.0 Units on a scale | Standard Deviation 7.07 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 48 | 0.0 Units on a scale | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 24 | 10.0 Units on a scale | Standard Deviation 7.07 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Baseline | 73.5 Units on a scale | Standard Deviation 9.19 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 24 | 15.0 Units on a scale | Standard Deviation 0 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 36 | 8.0 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 48 | 10.0 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 12 | 10.0 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 52 | 16.0 Units on a scale | Standard Deviation 1.41 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 52 | -10.0 Units on a scale | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 48 | 0.0 Units on a scale | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 60 | 4.5 Units on a scale | Standard Deviation 6.36 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 12 | 5.0 Units on a scale | Standard Deviation 21.21 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 24 | 19.5 Units on a scale | Standard Deviation 14.85 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Baseline | 80.0 Units on a scale | Standard Deviation 14.14 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 36 | 0.0 Units on a scale | — |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 24 | -3.0 Units on a scale | Standard Deviation 7.52 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 60 | -1.3 Units on a scale | Standard Deviation 9.07 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 12 | -0.4 Units on a scale | Standard Deviation 5.32 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 48 | -3.0 Units on a scale | Standard Deviation 3 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Baseline | 92.6 Units on a scale | Standard Deviation 10.67 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 36 | -0.7 Units on a scale | Standard Deviation 9.02 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Week 52 | -4.2 Units on a scale | Standard Deviation 6.57 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60 | Change at Month 24 | -4.0 Units on a scale | Standard Deviation 5.66 |
Secondary
Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60
EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health on a 5-point scale. Each dimension had 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and visual analogue scale (VAS). Index score was obtained, according to the health state defined by the 5 dimensions scores, from the Crosswalk Index value calculator and table lookup document under the target country population. A health state is defined by the combination of one level from each of the 5 dimensions. For this study, weights under the US population were used to obtain the Index score. Index score ranged between 0-1, where higher score indicates a better health state, and lower score indicate worse health state. Baseline was defined as the latest non-missing value before IP infusion.
Time frame: Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60
Population: Safety population. Here, Number Analyzed =participants evaluable for specified timepoints. Participants from Cohort 1: PF-07055480 9\*10\^11 vg/kg and Cohort 2: PF-07055480 2\*10\^12 vg/kg did not attend the study visit or missed the EQ-5D-5L assessment at Months 24 and 60 and participants from Cohort 3: PF-07055480 1\*10\^13 vg/kg did not attend the study visit or missed the EQ-5D-5L assessment at Month 24; hence, no participants were analyzed for Cohorts 1, 2 and 3 at the mentioned visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 36 | -0.099 Units on a scale | Standard Deviation 0.14 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 12 | 0.011 Units on a scale | Standard Deviation 0.016 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 24 | -0.033 Units on a scale | Standard Deviation 0.129 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Baseline | 0.902 Units on a scale | Standard Deviation 0.139 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 48 | -0.013 Units on a scale | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 52 | -0.165 Units on a scale | Standard Deviation 0.266 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Baseline | 0.577 Units on a scale | Standard Deviation 0.254 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 36 | 0.334 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 12 | 0.244 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 52 | 0.294 Units on a scale | Standard Deviation 0.071 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 48 | 0.219 Units on a scale | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 24 | 0.317 Units on a scale | Standard Deviation 0.103 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 36 | -0.210 Units on a scale | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Baseline | 0.922 Units on a scale | Standard Deviation 0.11 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 12 | 0.078 Units on a scale | Standard Deviation 0.11 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 52 | 0.000 Units on a scale | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 48 | -0.197 Units on a scale | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 60 | -0.087 Units on a scale | Standard Deviation 0.047 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 24 | 0.078 Units on a scale | Standard Deviation 0.11 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 24 | -0.036 Units on a scale | Standard Deviation 0.08 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 12 | 0.016 Units on a scale | Standard Deviation 0.035 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 60 | -0.053 Units on a scale | Standard Deviation 0.105 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 48 | 0.000 Units on a scale | Standard Deviation 0 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Baseline | 0.946 Units on a scale | Standard Deviation 0.122 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 24 | 0.000 Units on a scale | Standard Deviation 0 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Week 52 | -0.002 Units on a scale | Standard Deviation 0.004 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60 | Change at Month 36 | 0.000 Units on a scale | Standard Deviation 0 |
Secondary
Number of Participants With Positive FVIII Inhibitor Levels During the Study
Positive FVIII inhibitor was assessed using central laboratory using Nijmegen method of the Bethesda assay in an individual with no prior history of FVIII inhibitor. Inhibitor assay results \>0.6 Bethesda units (BU) were considered as positive. Positive results at any timepoint were considered, even if subsequent inhibitor assessment was negative.
Time frame: Baseline (one week prior to IP infusion) up to 5 years post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Number of Participants With Positive FVIII Inhibitor Levels During the Study | 1 Participants |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Number of Participants With Positive FVIII Inhibitor Levels During the Study | 0 Participants |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Number of Participants With Positive FVIII Inhibitor Levels During the Study | 0 Participants |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Number of Participants With Positive FVIII Inhibitor Levels During the Study | 0 Participants |
Secondary
Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine
Peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, semen, stool and urine were analyzed with quantitative real-time polymerase chain reaction (PCR). Participants must achieve 3 consecutive negative results for analysis for each sample.
Time frame: All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Saliva | 44550 Vector genome per milliliter (vg/mL) | Standard Deviation 21710 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Semen | 14600 Vector genome per milliliter (vg/mL) | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Stool | 604 Vector genome per milliliter (vg/mL) | Standard Deviation 407.3 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Plasma | 25680000 Vector genome per milliliter (vg/mL) | Standard Deviation 26620000 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Plasma | 292600000 Vector genome per milliliter (vg/mL) | Standard Deviation 383900000 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Saliva | 159500 Vector genome per milliliter (vg/mL) | Standard Deviation 89870 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Semen | 36500 Vector genome per milliliter (vg/mL) | — |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Semen | 145500 Vector genome per milliliter (vg/mL) | Standard Deviation 4950 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Saliva | 1555000 Vector genome per milliliter (vg/mL) | Standard Deviation 417200 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Plasma | 1787000000 Vector genome per milliliter (vg/mL) | Standard Deviation 1390000000 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Stool | 2490 Vector genome per milliliter (vg/mL) | Standard Deviation 2461 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Saliva | 6972000 Vector genome per milliliter (vg/mL) | Standard Deviation 5158000 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Semen | 99780 Vector genome per milliliter (vg/mL) | Standard Deviation 151900 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Stool | 2277 Vector genome per milliliter (vg/mL) | Standard Deviation 2814 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Urine | 9697 Vector genome per milliliter (vg/mL) | Standard Deviation 6166 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine | Plasma | 3442000000 Vector genome per milliliter (vg/mL) | Standard Deviation 2809000000 |
Secondary
Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine
Time to last of 3 consecutive negative value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR.
Time frame: All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 56.0 Days | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 85.0 Days | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 28.5 Days | Standard Deviation 0.71 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 55.5 Days | Standard Deviation 40.31 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 71.0 Days | Standard Deviation 19.8 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 57.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 84.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 29.0 Days | Standard Deviation 0 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 84.5 Days | Standard Deviation 0.71 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 57.0 Days | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 115.5 Days | Standard Deviation 43.13 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 113.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 113.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 115.5 Days | Standard Deviation 43.13 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 28.5 Days | Standard Deviation 0.71 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 185.6 Days | Standard Deviation 164.77 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 105.3 Days | Standard Deviation 27.6 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 166.7 Days | Standard Deviation 92.95 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 95.4 Days | Standard Deviation 31.41 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 45.4 Days | Standard Deviation 14.99 |
Secondary
Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine
Time to last positive value prior to first of 3 consecutive negatives of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR, where positive suggests values above the limit of detection.
Time frame: All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 15.5 Days | Standard Deviation 0.71 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 8.0 Days | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 11.5 Days | Standard Deviation 4.95 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 15.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 15.0 Days | Standard Deviation 0 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 7.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 28.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 21.5 Days | Standard Deviation 9.19 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 21.5 Days | Standard Deviation 9.19 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 28.5 Days | Standard Deviation 0.71 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 9.7 Days | Standard Deviation 3.79 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 35.5 Days | Standard Deviation 14.34 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 18.6 Days | Standard Deviation 9.56 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 47.3 Days | Standard Deviation 31.75 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 21.4 Days | Standard Deviation 9.66 |
Secondary
Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine
Time to peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Participants must achieve 3 consecutive negative results for analysis for each sample; where negative suggests values under the limit of detection.
Time frame: All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 1.5 Days | Standard Deviation 0.71 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 11.5 Days | Standard Deviation 4.95 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 8.0 Days | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 8.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 7.5 Days | Standard Deviation 0.71 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 15.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 1.0 Days | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 1.0 Days | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 11.0 Days | Standard Deviation 4.24 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 7.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 12.0 Days | Standard Deviation 4.24 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 1.4 Days | Standard Deviation 0.55 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 14.4 Days | Standard Deviation 8.99 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 17.0 Days | Standard Deviation 10.32 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 9.7 Days | Standard Deviation 3.79 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 11.8 Days | Standard Deviation 3.96 |
Secondary
Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine
Time to undetectable (negative) value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Time to undetectable is defined as the number of days from IP infusion until the first of 3 consecutive specimens under the limit of detection (negative).
Time frame: All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Population: Safety population included all participants enrolled in this study who received any portion of study intervention. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 15.0 Days | — |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 28.5 Days | Standard Deviation 0.71 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 8.0 Days | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 18.0 Days | Standard Deviation 14.14 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 22.0 Days | Standard Deviation 8.49 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 15.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 15.0 Days | — |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 7.5 Days | Standard Deviation 0.71 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 29.0 Days | Standard Deviation 0 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 15.0 Days | Standard Deviation 0 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 42.0 Days | Standard Deviation 18.38 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 56.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 56.5 Days | Standard Deviation 0.71 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 42.0 Days | Standard Deviation 18.38 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 8.5 Days | Standard Deviation 0.71 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Stool | 72.6 Days | Standard Deviation 62.1 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Saliva | 60.5 Days | Standard Deviation 17.62 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Plasma | 84.7 Days | Standard Deviation 47.92 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Semen | 42.2 Days | Standard Deviation 27.51 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine | Urine | 14.8 Days | Standard Deviation 8.17 |
Secondary
Total ABR by Severity
Total ABR include both treated and untreated bleeding episodes. In this outcome measure total ABR by severity for post-infusion period is reported. Severity was categorized as mild, moderate and severe. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after IP infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used.
Time frame: Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Total ABR by Severity | Mild | 7.93 Bleeds per year | Standard Deviation 3.139 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Total ABR by Severity | Severe | 0.00 Bleeds per year | Standard Deviation 0 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Total ABR by Severity | Moderate | 0.00 Bleeds per year | Standard Deviation 0 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Total ABR by Severity | Mild | 0.87 Bleeds per year | Standard Deviation 0.081 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Total ABR by Severity | Severe | 0.47 Bleeds per year | Standard Deviation 0.658 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Total ABR by Severity | Moderate | 1.73 Bleeds per year | Standard Deviation 2.159 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Total ABR by Severity | Moderate | 3.07 Bleeds per year | Standard Deviation 4.345 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Total ABR by Severity | Mild | 0.17 Bleeds per year | Standard Deviation 0.241 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Total ABR by Severity | Severe | 0.00 Bleeds per year | Standard Deviation 0 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Total ABR by Severity | Mild | 1.22 Bleeds per year | Standard Deviation 2.725 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Total ABR by Severity | Severe | 0.00 Bleeds per year | Standard Deviation 0 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Total ABR by Severity | Moderate | 0.31 Bleeds per year | Standard Deviation 0.528 |
Secondary
Total Annualized Bleeding Rate (ABR)
Total ABR included both treated and untreated bleeding episodes. In this outcome measure total ABR for pre-screening and post-infusion are reported. Pre-screening total ABR was based on the total number of reported bleeding episodes during 12 months prior to screening visit as reported on CRF's Hemophilia A History page. Screening was 2 months before baseline. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after investigational product/ PF-07055480 (IP) infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used.
Time frame: Pre-screening period: 12 months prior to screening; Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years)
Population: Safety population included all participants enrolled in this study who received any portion of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-07055480 9*10^11 vg/kg | Total Annualized Bleeding Rate (ABR) | Pre-screening total ABR | 3.50 Bleeds per year | Standard Deviation 0.707 |
| Cohort 1: PF-07055480 9*10^11 vg/kg | Total Annualized Bleeding Rate (ABR) | Post infusion total ABR -until prophylaxis is resumed | 7.93 Bleeds per year | Standard Deviation 3.139 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Total Annualized Bleeding Rate (ABR) | Post infusion total ABR -until prophylaxis is resumed | 3.07 Bleeds per year | Standard Deviation 2.898 |
| Cohort 2: PF-07055480 2*10^12 vg/kg | Total Annualized Bleeding Rate (ABR) | Pre-screening total ABR | 14.00 Bleeds per year | Standard Deviation 16.971 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Total Annualized Bleeding Rate (ABR) | Pre-screening total ABR | 1.50 Bleeds per year | Standard Deviation 2.121 |
| Cohort 3: PF-07055480 1*10^13 vg/kg | Total Annualized Bleeding Rate (ABR) | Post infusion total ABR -until prophylaxis is resumed | 3.24 Bleeds per year | Standard Deviation 4.586 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Total Annualized Bleeding Rate (ABR) | Pre-screening total ABR | 8.80 Bleeds per year | Standard Deviation 8.319 |
| Cohort 4: PF-07055480 3*10^13 vg/kg | Total Annualized Bleeding Rate (ABR) | Post infusion total ABR -until prophylaxis is resumed | 1.53 Bleeds per year | Standard Deviation 3.235 |