Hemophilia A
Conditions
Keywords
PF-07055480, SB-525, Hemophilia, Factor VIII, FVIII, Gene Therapy, AAV, AAV6, Annualized bleeding rate, ABR, giroctocogene fitelparvovec, AFFINE
Brief summary
C3731003 is a pivotal Phase 3 study to evaluate the clinical efficacy and safety of a single IV infusion of PF-07055480 / giroctocogene fitelparvovec (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in adult male participants with moderately severe or severe hemophilia A (FVIII:C≤1%) for the study duration of 5 years. The study will enroll eligible participants who have been followed on routine prophylaxis with FVIII products in the Lead-In study C0371004.
Interventions
BIOLOGICALPF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy
Single IV infusion
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion Criteria * Males who have been followed on routine Factor VIII prophylaxis therapy during the lead-in study (C0371004) and have \> = 150 documented exposure days to a Factor VIII protein product * Moderately severe to severe hemophilia A (Factor VIII activity \< =1%) * Suspension of FVIII prophylaxis therapy post study drug infusion Main
Exclusion criteria
* Anti-AAV6 neutralizing antibodies * History of inhibitor to Factor VIII * Laboratory values at screening visit that are abnormal or outside acceptable study limits * Significant and/or unstable liver disease, biliary disease, significant liver fibrosis * Conditions associated with increased thromboembolic risk such as inherited or acquired thrombophilia, or a history of thrombotic events * Planned surgical procedure requiring Factor VIII surgical prophylactic factor treatment 12 months from screening visit * Active hepatitis B or C * Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 and/or viral load \>20 copies/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Annualized Bleeding Rate (ABR) | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: bleeding event did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. In this outcome measure total ABR following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. Total ABR for FVIII prophylaxis= \[(Number of total bleeding episodes during pre-infusion period)\*365.25\]/ \[(Number of days of follow-up in pre-infusion period)\]. Total ABR for PF-07055480: \[(Number of total bleeding episodes during post-infusion period)\*365.25\] / \[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Coagulation FVIII Activity Levels Greater Than (>)5 Percent (%) at 15 Months | At 15 months following infusion of PF-07055480 | FVIII activity level based on central laboratory chromogenic assay at Month 15 |
| Treated ABR | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Treated bleed was defined as an event which necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure treated ABR following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. Treated ABR for FVIII prophylaxis= \[(Number of treated bleeding episodes during pre-infusion period)\*365.25\]/ \[(Number of days of follow-up in pre-infusion period)\]. Treated ABR for PF-07055480: \[(Number of treated bleeding episodes during post-infusion period)\*365.25\] / \[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\]. |
| Annualized Infusion Rate (AIR) of Exogenous FVIII Activity | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period) \* 365.25\]/ (Number of days of follow-up in the given time period). In this outcome measure AIR of exogenous FVIII activity in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. |
| FVIII Activity Levels From Week 12 Through 15 Months Following PF-07055480 Infusion | Week 12 through Month 15 following PF-07055480 Infusion | FVIII activity levels were assessed using chromogenic assay and one-stage clotting assay analyzed in the central laboratory. As pre-specified, for each participant, a geometric mean laboratory reading for FVIII activity was used to derived one single FVIII level by including all assessments from Week 12 through 15 months following PF-07055480 infusion; then mean and standard deviation as summary statistics was calculated across all evaluable participants and reported as data for this outcome measure. This resulting Factor VIII activity is expressed as percent of normal (%); which is used interchangeable with international unit per deciliter (IU/dL). "Normal Range" is typically considered 50-150% (or 50-150 IU/dL). |
| Annualized FVIII Consumption | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Annualized FVIII consumption was reported in international units per kilogram (IU/kg) and total units (in IU). This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003. Data is reported in this outcome measure as mean of annualized FVIII consumption from all participants in this analysis population. |
| Total (Treated and Untreated) ABR Based on Cause | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Bleeds based on cause:spontaneous(bleeding for no apparent/known reason particularly into the joint,muscles and soft tissue)and traumatic(bleeding event occurring for an apparent/known reason).Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedure,or invasive diagnostic procedures were not counted as bleeds.Treated:necessitated administration of coagulation factor within 72hrs of sign or symptom of bleeding. Untreated:did not necessitate administration of coagulation factor within 72hrs of sign and symptom of bleeding.ABR for FVIII prophylaxis=\[(Number of total bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion period).ABR for PF-07055480\[(Number of total bleeding episodes during post-infusion period)\*365.25\]/\[(last date of post-infusion period-date of PF-07055480 infusion)-77 days+1\].This outcome measure compared data collected from lead-inC0371004and from current studyC3731003. |
| Treated ABR Based on Cause | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissues) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic procedure were not counted as bleeds. Treated: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Treated ABR for FVIII prophylaxis= \[(Number of treated bleeding episodes during pre-infusion period)\*365.25\]/ (Number of days of follow-up in pre-infusion period). Treated ABR for PF-07055480: \[(Number of treated bleeding episodes during post-infusion period)\*365.25\] /\[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\]. This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003. |
| Annualized FVIII Consumption Yearly | Maximum up to 5 years post PF-07055480 infusion | Annualized FVIII consumption will be reported in IU/kg and total units (in IU). |
| Total (Treated and Untreated) ABR Based on Location | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Target joint:major joint(hip,elbow,wrist,shoulder,knee\&ankle)with repeated bleed(3 or more spontaneous bleed into a single joint within6month).Joint bleed:bleeding episode by rapid loss of motion as compared with baseline,associated with pain or unusual sensation,swelling\&warmth over the joint.Muscle:bleeding episode into a muscle,determined by imaging study,associated with pain\&or swelling \&functional impairment.Treated:necessitated administration of coagulation factor within72hrs of sign or symptom of bleeding.Untreated:did not necessitate administration of coagulation factor within72hrs of sign\&symptom of bleeding.FVIII prophylaxis=\[(Number of total bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion).PF-07055480:\[(Number of total bleeding episodes during post-infusion)\*365.25\]/\[(last date of post infusion-date of PF-07055480 infusion)-77days+1\].This outcome measure compared data collected from lead-inC0371004 and from current studyC3731003. |
| Treated ABR Based on Location | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Target joint:major joint(hip,elbow,wrist,shoulder,knee,and ankle)with repeated bleeds(3 or more spontaneous bleeds into a single joint within 6month).Joint bleed:bleeding episode characterized by rapid loss of range of motion as compared with baseline,associated with pain or an unusual sensation in the joint,palpable swelling,and warmth of the skin over the joint.Muscle:bleeding episode into a muscle,determined clinically and/or by imaging study,associated with pain and/or swelling and functional impairment.Treated:necessitated administration of coagulation factor within72 hrs of sign or symptom of bleeding.FVIII prophylaxis=\[(Number of treated bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion).PF-07055480:\[(Number of treated bleeding episodes during post-infusion)\*365.25\]/\[(last date of post-infusion-date of PF-07055480 infusion)-77days+1\].This outcome measure compared data collected from lead-in studyC0371004 and from current studyC3731003. |
| Percentage of Participants Without Bleeds | FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period) | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. In this outcome measure percentage of participants without bleeds following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion) were reported. This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003. |
| FVIII Activity Level at Weeks 24, 52, 65, and 104 | At Weeks 24, 52, 65 and 104 | FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. |
| Change From Baseline in Joint Health as Measured by Hemophilia Joint Health Score (HJHS) Instrument at Weeks 24 and 52 | Baseline (before infusion on Day 1); Weeks 24 and 52 | A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total HJHS score = sum of scores from all six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) + gait score, ranged from 0 to 124, with the higher score indicated the number equating to more severe joint damage. |
| Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52 | Baseline (before infusion on Day 1); Weeks 12, 24 and 52 | Haem-A-QoL assessed health-related quality of life in adult participants with hemophilia. It contains 46 items with 10 domains that assesses health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with Haemophilia; treatment; future; family planning; and partnership and sexuality. All items are based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring is performed by averaging non-missing item responses for each domain, then rescaled to be on 0 to 100, with lower scores representing higher quality of life. Total score= was averaged across the 46 items values and then rescaled on 0 to 100, with lower scores representing better quality of life and physical health status. Change from baseline in physical Health domain score was reported in this outcome measure. |
| Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52 | Baseline (before infusion on Day 1); Weeks 12, 24 and 52 | The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows:lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was calculated according to the Van Genderen scoring algorithm, had a transformed score range from 0 to 100; higher scores indicate better quality of life, that is, less functional limitations in performing tasks. Change from baseline in complex lower extremity activities component score was reported in this outcome measure. |
| ABR for Total Bleeds (Treated and Untreated) Yearly | Maximum up to 5 years post PF-07055480 infusion | Treated ABR: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). Untreated ABR: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| FVIII Activity Levels Yearly | Maximum up to 5 years post PF-07055480 infusion | FVIII activity levels will be assessed using one stage assay and chromogenic assay in the central lab. |
| AIR of Exogenous FVIII Yearly | Maximum up to 5 years post PF-07055480 infusion | AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period)\* 365.25\]/ (Number of days of follow-up in the given time period). |
| Total (Treated and Untreated) ABR Based on Cause Yearly | Maximum up to 5 years post PF-07055480 infusion | Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Treated ABR Based on Cause Yearly | Maximum up to 5 years post PF-07055480 infusion | Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. |
| Total (Treated and Untreated) ABR Based on Location Yearly | Maximum up to 5 years post PF-07055480 infusion | Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleed into a single joint within 6 month). Joint bleed: bleeding episode by rapid loss of range of motion compared with baseline, associated with pain or an unusual sensation in the joint, swelling. Muscle bleed: bleeding episode into a muscle, determined by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hrs of sign and symptom of bleeding. |
| Treated ABR Based on Location Yearly | Maximum up to 5 years post PF-07055480 infusion | Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleed into a single joint within 6 month). Joint bleed: bleeding episode by rapid loss of range of motion compared with baseline, associated with pain or an unusual sensation in the joint, swelling. Muscle bleed: bleeding episode into a muscle, determined by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. |
| Total (Treated and Untreated) ABR Yearly | Maximum up to 5 years post PF-07055480 infusion | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Treated ABR by Yearly | Maximum up to 5 years post PF-07055480 infusion | Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. |
| Percentage of Participants Without Bleeds Yearly | Maximum up to 5 years post PF-07055480 infusion | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Change From Baseline in Joint HJHS Instrument Yearly | Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion | A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total score = sum of scores from all joints + gait score, ranged from 0 to 124, with the higher score indicated the number equating to more severe joint damage. |
| Change From Baseline in Haem-A-QoL for Adults Physical Health Domain Score Yearly | Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion | Haem-A-QoL assessed health-related quality of life in adult participants with hemophilia. It contains 46 items with 10 domains that assesses health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with Haemophilia; treatment; future; family planning; and partnership and sexuality. All items are based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring is performed by averaging non-missing item responses for each domain, then rescaled to be on 0 to 100, with lower scores representing higher quality of life. Total score= was averaged across the 46 items values and then rescaled on 0 to 100, with lower scores representing better quality of life and physical health status. Change from baseline in physical Health domain score will be reported in this outcome measure. |
| Change From Baseline in HAL Complex Lower Extremity Activities Component Score Yearly | Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion | The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows:lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was calculated according to the Van Genderen scoring algorithm, had a transformed score range from 0 to 100; higher scores indicate better quality of life, that is, less functional limitations in performing tasks. Change from baseline in complex lower extremity activities component score will be reported in this outcome measure. |
| Treated ABR by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Treated ABR: an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. |
| Treated ABR Based on Cause by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. |
| Treated ABR Based on Location by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Target joint based on location: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleeds into a single joint within a consecutive 6-month period). Joint bleed: bleeding episode characterized by rapid loss of range of motion as compared with baseline, associated with pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. Muscle bleed: bleeding episode into a muscle, determined clinically and/or by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. |
| AIR of Exogenous FVIII by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period)\* 365.25\]/ (Number of days of follow-up in the given time period). |
| Annualized FVIII Consumption by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Annualized FVIII consumption will be reported in IU/kg and total units (in IU). |
| Total (Treated and Untreated) ABR Based on Cause by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleeds: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleeds: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Total (Treated and Untreated) ABR Based on Location by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) into which repeated bleeds occurred (3 or more spontaneous bleeds into a single joint within a consecutive 6month period). Target joint was considered resolved when there were =\<2 bleed into the joint within a 12-month period. Joint bleed: A bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of the following: pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. Muscle bleed: an episode of bleeding into a muscle, determined clinically and/or by imaging studies, generally associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hrs of sign and symptom of bleeding. |
| Percentage of Participants Without Bleeds by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Total ABR (Treated and Untreated) by Cumulative Follow-up Interval | Maximum up to 5 years post PF-07055480 infusion | Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: bleeding event did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. |
| Number of Participants With Adverse Events (AEs) and Severe AEs | From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months) | An AEs 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. Severe AEs: An event that prevented normal everyday activities. Severe was a category utilized for rating the intensity of an event, and both AEs and serious adverse events (SAEs) could be assessed as severe. |
| Number of Participants With AEs of Special Interest | From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months) | 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. AESI included all medically important events that were reported as a serious adverse events (SAE), and any clinical reported thrombotic event or hypersensitivity/infusion-related reactions events assessed as non-serious AEs. |
| Number of Participants With Positive Antibodies Against Adeno-Associated Virus Vector 6 (AAV6) Capsid Protein | Maximum up to 5 years post PF-07055480 infusion | Number of participants with positive antibodies against AAV6 Capsid protein will be reported in this outcome measure. |
| Number of Participants With T-cell Responses Against AAV6 Capsid and FVIII by Elispot Assay | Maximum up to 5 years post PF-07055480 infusion | The enzyme linked immune spot (ELISPOT) assay is a highly sensitive quantitative immunoassay for measuring relevant parameters of T cell activation (the frequency of cytokine-secreting cells at the single-cell level) on peripheral blood mononuclear cells (PBMC). T cell responses to AAV6 and FVIII will be evaluated at baseline and during study follow up, if corticosteroid treatment is needed for a suspected T-cell response. |
| Number of Participants With FVIII Inhibitors Status by Bethesda Assessment | Maximum up to 5 years post PF-07055480 infusion | Nijmegen Bethesda assay will be used to assess the presence of FVIII inhibitors (Inhibitory antibodies against FVIII that neutralize the clotting activity of FVIII). Positive refers to FVIII inhibitor levels by inhibitor assay results \>=0.6 Bethesda units per milliliter (BU/mL). |
Countries
Australia, Brazil, Canada, France, Germany, Greece, Italy, Japan, Saudi Arabia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
Participants with moderately severe to severe hemophilia A, who completed routine Factor VIII (FVIII) prophylaxis follow-up during the lead-in study C0371004 (NCT03587116), were enrolled in this study. Participants in this study received single infusion of PF-07055480/giroctocogene fitelparovec.
Pre-assignment details
Results are presented for primary outcome measures and only those secondary outcome measures whose analysis was complete on a data cutoff date of 17 June 2024 (primary completion date \[PCD\]). Remaining outcome measures would be reported upon completion of their analyses at study completion date.
Participants by arm
| Arm | Count |
|---|---|
| PF-07055480 Participants received a single infusion of PF-07055480 3.0\*10\^13 vg/kg IV on Day 1. | 75 |
| Total | 75 |
Baseline characteristics
| Characteristic | PF-07055480 |
|---|---|
| Age, Continuous | 32.27 Years STANDARD_DEVIATION 10.441 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 56 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 75 |
| other Total, other adverse events | 70 / 75 |
| serious Total, serious adverse events | 15 / 75 |
Outcome results
Primary
Total Annualized Bleeding Rate (ABR)
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: bleeding event did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. In this outcome measure total ABR following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. Total ABR for FVIII prophylaxis= \[(Number of total bleeding episodes during pre-infusion period)\*365.25\]/ \[(Number of days of follow-up in pre-infusion period)\]. Total ABR for PF-07055480: \[(Number of total bleeding episodes during post-infusion period)\*365.25\] / \[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\].
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FVIII Prophylaxis | Total Annualized Bleeding Rate (ABR) | 4.73 Total bleeds per year |
| PF-07055480 | Total Annualized Bleeding Rate (ABR) | 1.24 Total bleeds per year |
Comparison: A repeated measures GLM was used with bleeds as dependent variable in negative binomial distribution, an interaction of duration by treatment, and 'participant' as random and treatment \& duration of follow-up as fixed effect.p-value: =0.00495% CI: [-6.06, -0.91]Generalized linear model (GLM)
Secondary
ABR for Total Bleeds (Treated and Untreated) Yearly
Treated ABR: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). Untreated ABR: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
AIR of Exogenous FVIII by Cumulative Follow-up Interval
AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period)\* 365.25\]/ (Number of days of follow-up in the given time period).
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
AIR of Exogenous FVIII Yearly
AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period)\* 365.25\]/ (Number of days of follow-up in the given time period).
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Annualized FVIII Consumption
Annualized FVIII consumption was reported in international units per kilogram (IU/kg) and total units (in IU). This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003. Data is reported in this outcome measure as mean of annualized FVIII consumption from all participants in this analysis population.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FVIII Prophylaxis | Annualized FVIII Consumption | 4082.7 IU/kg | Standard Deviation 2291.9 |
| PF-07055480 | Annualized FVIII Consumption | 6.6 IU/kg | Standard Deviation 21.41 |
p-value: <0.000195% CI: [-4728.3, -3423.8]Paired t-test
Secondary
Annualized FVIII Consumption by Cumulative Follow-up Interval
Annualized FVIII consumption will be reported in IU/kg and total units (in IU).
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Annualized FVIII Consumption Yearly
Annualized FVIII consumption will be reported in IU/kg and total units (in IU).
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Annualized Infusion Rate (AIR) of Exogenous FVIII Activity
AIR: \[(Number of exogenous FVIII product infusions for any purpose during the given time period) \* 365.25\]/ (Number of days of follow-up in the given time period). In this outcome measure AIR of exogenous FVIII activity in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FVIII Prophylaxis | Annualized Infusion Rate (AIR) of Exogenous FVIII Activity | 124.39 Exogenous infusions per year | Standard Deviation 53.882 |
| PF-07055480 | Annualized Infusion Rate (AIR) of Exogenous FVIII Activity | 0.21 Exogenous infusions per year | Standard Deviation 0.601 |
p-value: <0.000195% CI: [-139.47, 108.89]Paired t-test
Secondary
Change From Baseline in Haem-A-QoL for Adults Physical Health Domain Score Yearly
Haem-A-QoL assessed health-related quality of life in adult participants with hemophilia. It contains 46 items with 10 domains that assesses health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with Haemophilia; treatment; future; family planning; and partnership and sexuality. All items are based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring is performed by averaging non-missing item responses for each domain, then rescaled to be on 0 to 100, with lower scores representing higher quality of life. Total score= was averaged across the 46 items values and then rescaled on 0 to 100, with lower scores representing better quality of life and physical health status. Change from baseline in physical Health domain score will be reported in this outcome measure.
Time frame: Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
Secondary
Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52
Haem-A-QoL assessed health-related quality of life in adult participants with hemophilia. It contains 46 items with 10 domains that assesses health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with Haemophilia; treatment; future; family planning; and partnership and sexuality. All items are based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring is performed by averaging non-missing item responses for each domain, then rescaled to be on 0 to 100, with lower scores representing higher quality of life. Total score= was averaged across the 46 items values and then rescaled on 0 to 100, with lower scores representing better quality of life and physical health status. Change from baseline in physical Health domain score was reported in this outcome measure.
Time frame: Baseline (before infusion on Day 1); Weeks 12, 24 and 52
Population: Dosed analysis population included all participants enrolled in the study and who received the study intervention. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FVIII Prophylaxis | Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52 | Change at Week 12 | -13.56 Units on a scale |
| FVIII Prophylaxis | Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52 | Change at Week 24 | -14.10 Units on a scale |
| FVIII Prophylaxis | Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52 | Change at Week 52 | -9.63 Units on a scale |
Secondary
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Yearly
The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows:lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was calculated according to the Van Genderen scoring algorithm, had a transformed score range from 0 to 100; higher scores indicate better quality of life, that is, less functional limitations in performing tasks. Change from baseline in complex lower extremity activities component score will be reported in this outcome measure.
Time frame: Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
Secondary
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52
The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows:lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was calculated according to the Van Genderen scoring algorithm, had a transformed score range from 0 to 100; higher scores indicate better quality of life, that is, less functional limitations in performing tasks. Change from baseline in complex lower extremity activities component score was reported in this outcome measure.
Time frame: Baseline (before infusion on Day 1); Weeks 12, 24 and 52
Population: Dosed analysis population included all participants enrolled in the study and who receive the study intervention. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FVIII Prophylaxis | Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52 | Change at Week 12 | 3.1 Units on a scale |
| FVIII Prophylaxis | Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52 | Change at Week 24 | 3.0 Units on a scale |
| FVIII Prophylaxis | Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52 | Change at Week 52 | 2.5 Units on a scale |
Secondary
Change From Baseline in Joint Health as Measured by Hemophilia Joint Health Score (HJHS) Instrument at Weeks 24 and 52
A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total HJHS score = sum of scores from all six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) + gait score, ranged from 0 to 124, with the higher score indicated the number equating to more severe joint damage.
Time frame: Baseline (before infusion on Day 1); Weeks 24 and 52
Population: Dosed analysis population included all participants enrolled in the study and who received the study intervention. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for at specific timepoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FVIII Prophylaxis | Change From Baseline in Joint Health as Measured by Hemophilia Joint Health Score (HJHS) Instrument at Weeks 24 and 52 | Change at Week 24 | -1.4 Units on a scale |
| FVIII Prophylaxis | Change From Baseline in Joint Health as Measured by Hemophilia Joint Health Score (HJHS) Instrument at Weeks 24 and 52 | Change at Week 52 | -2.4 Units on a scale |
Secondary
Change From Baseline in Joint HJHS Instrument Yearly
A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total score = sum of scores from all joints + gait score, ranged from 0 to 124, with the higher score indicated the number equating to more severe joint damage.
Time frame: Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
Secondary
FVIII Activity Level at Weeks 24, 52, 65, and 104
FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory.
Time frame: At Weeks 24, 52, 65 and 104
Population: Dosed analysis population included all participants enrolled in the study and who received the study intervention. Here Number Analyzed at each row represents the number of participants with valid FVIII assessments at the respective time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 24: One-Stage Assay | 147.14 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 52: Chromogenic Assay | 51.68 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 52: One-Stage Assay | 80.14 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 65: Chromogenic Assay | 51.08 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 65: One-Stage Assay | 73.99 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 104: Chromogenic Assay | 51.90 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 104: One-Stage Assay | 72.91 Percentage of Normal |
| FVIII Prophylaxis | FVIII Activity Level at Weeks 24, 52, 65, and 104 | Week 24: Chromogenic Assay | 101.59 Percentage of Normal |
Secondary
FVIII Activity Levels From Week 12 Through 15 Months Following PF-07055480 Infusion
FVIII activity levels were assessed using chromogenic assay and one-stage clotting assay analyzed in the central laboratory. As pre-specified, for each participant, a geometric mean laboratory reading for FVIII activity was used to derived one single FVIII level by including all assessments from Week 12 through 15 months following PF-07055480 infusion; then mean and standard deviation as summary statistics was calculated across all evaluable participants and reported as data for this outcome measure. This resulting Factor VIII activity is expressed as percent of normal (%); which is used interchangeable with international unit per deciliter (IU/dL). Normal Range is typically considered 50-150% (or 50-150 IU/dL).
Time frame: Week 12 through Month 15 following PF-07055480 Infusion
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FVIII Prophylaxis | FVIII Activity Levels From Week 12 Through 15 Months Following PF-07055480 Infusion | Chromogenic Assay | 96.84 Percentage of Normal | Standard Deviation 90.521 |
| FVIII Prophylaxis | FVIII Activity Levels From Week 12 Through 15 Months Following PF-07055480 Infusion | One-Stage Assay | 134.95 Percentage of Normal | Standard Deviation 116.161 |
Secondary
FVIII Activity Levels Yearly
FVIII activity levels will be assessed using one stage assay and chromogenic assay in the central lab.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Number of Participants With Adverse Events (AEs) and Severe AEs
An AEs 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. Severe AEs: An event that prevented normal everyday activities. Severe was a category utilized for rating the intensity of an event, and both AEs and serious adverse events (SAEs) could be assessed as severe.
Time frame: From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months)
Population: Safety population included all participants enrolled in the study who received the study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FVIII Prophylaxis | Number of Participants With Adverse Events (AEs) and Severe AEs | AEs | 74 Participants |
| FVIII Prophylaxis | Number of Participants With Adverse Events (AEs) and Severe AEs | Severe AEs | 7 Participants |
Secondary
Number of Participants With AEs of Special Interest
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. AESI included all medically important events that were reported as a serious adverse events (SAE), and any clinical reported thrombotic event or hypersensitivity/infusion-related reactions events assessed as non-serious AEs.
Time frame: From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months)
Population: Safety population included all participants enrolled in the study who received the study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FVIII Prophylaxis | Number of Participants With AEs of Special Interest | 70 Participants |
Secondary
Number of Participants With FVIII Inhibitors Status by Bethesda Assessment
Nijmegen Bethesda assay will be used to assess the presence of FVIII inhibitors (Inhibitory antibodies against FVIII that neutralize the clotting activity of FVIII). Positive refers to FVIII inhibitor levels by inhibitor assay results \>=0.6 Bethesda units per milliliter (BU/mL).
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Number of Participants With Positive Antibodies Against Adeno-Associated Virus Vector 6 (AAV6) Capsid Protein
Number of participants with positive antibodies against AAV6 Capsid protein will be reported in this outcome measure.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Number of Participants With T-cell Responses Against AAV6 Capsid and FVIII by Elispot Assay
The enzyme linked immune spot (ELISPOT) assay is a highly sensitive quantitative immunoassay for measuring relevant parameters of T cell activation (the frequency of cytokine-secreting cells at the single-cell level) on peripheral blood mononuclear cells (PBMC). T cell responses to AAV6 and FVIII will be evaluated at baseline and during study follow up, if corticosteroid treatment is needed for a suspected T-cell response.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Percentage of Participants With Coagulation FVIII Activity Levels Greater Than (>)5 Percent (%) at 15 Months
FVIII activity level based on central laboratory chromogenic assay at Month 15
Time frame: At 15 months following infusion of PF-07055480
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FVIII Prophylaxis | Percentage of Participants With Coagulation FVIII Activity Levels Greater Than (>)5 Percent (%) at 15 Months | 84.00 Percentage of participants |
p-value: =0.0086One-sided exact binomial proportion test
Secondary
Percentage of Participants Without Bleeds
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. In this outcome measure percentage of participants without bleeds following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion) were reported. This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FVIII Prophylaxis | Percentage of Participants Without Bleeds | Without treated bleeds | 30 Percentage of participants |
| FVIII Prophylaxis | Percentage of Participants Without Bleeds | Without treated and untreated bleeds | 26 Percentage of participants |
| PF-07055480 | Percentage of Participants Without Bleeds | Without treated bleeds | 88 Percentage of participants |
| PF-07055480 | Percentage of Participants Without Bleeds | Without treated and untreated bleeds | 64 Percentage of participants |
Secondary
Percentage of Participants Without Bleeds by Cumulative Follow-up Interval
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Percentage of Participants Without Bleeds Yearly
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total ABR (Treated and Untreated) by Cumulative Follow-up Interval
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: bleeding event did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total (Treated and Untreated) ABR Based on Cause
Bleeds based on cause:spontaneous(bleeding for no apparent/known reason particularly into the joint,muscles and soft tissue)and traumatic(bleeding event occurring for an apparent/known reason).Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedure,or invasive diagnostic procedures were not counted as bleeds.Treated:necessitated administration of coagulation factor within 72hrs of sign or symptom of bleeding. Untreated:did not necessitate administration of coagulation factor within 72hrs of sign and symptom of bleeding.ABR for FVIII prophylaxis=\[(Number of total bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion period).ABR for PF-07055480\[(Number of total bleeding episodes during post-infusion period)\*365.25\]/\[(last date of post-infusion period-date of PF-07055480 infusion)-77 days+1\].This outcome measure compared data collected from lead-inC0371004and from current studyC3731003.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FVIII Prophylaxis | Total (Treated and Untreated) ABR Based on Cause | Spontaneous | 3.27 Bleeds per year | Standard Deviation 5.591 |
| FVIII Prophylaxis | Total (Treated and Untreated) ABR Based on Cause | Traumatic | 1.46 Bleeds per year | Standard Deviation 3.416 |
| PF-07055480 | Total (Treated and Untreated) ABR Based on Cause | Spontaneous | 1.07 Bleeds per year | Standard Deviation 6.54 |
| PF-07055480 | Total (Treated and Untreated) ABR Based on Cause | Traumatic | 0.14 Bleeds per year | Standard Deviation 0.32 |
Secondary
Total (Treated and Untreated) ABR Based on Cause by Cumulative Follow-up Interval
Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleeds: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleeds: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total (Treated and Untreated) ABR Based on Cause Yearly
Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total (Treated and Untreated) ABR Based on Location
Target joint:major joint(hip,elbow,wrist,shoulder,knee&ankle)with repeated bleed(3 or more spontaneous bleed into a single joint within6month).Joint bleed:bleeding episode by rapid loss of motion as compared with baseline,associated with pain or unusual sensation,swelling&warmth over the joint.Muscle:bleeding episode into a muscle,determined by imaging study,associated with pain&or swelling &functional impairment.Treated:necessitated administration of coagulation factor within72hrs of sign or symptom of bleeding.Untreated:did not necessitate administration of coagulation factor within72hrs of sign&symptom of bleeding.FVIII prophylaxis=\[(Number of total bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion).PF-07055480:\[(Number of total bleeding episodes during post-infusion)\*365.25\]/\[(last date of post infusion-date of PF-07055480 infusion)-77days+1\].This outcome measure compared data collected from lead-inC0371004 and from current studyC3731003.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FVIII Prophylaxis | Total (Treated and Untreated) ABR Based on Location | All Joints | 3.28 Bleeds per year | Standard Deviation 5.358 |
| FVIII Prophylaxis | Total (Treated and Untreated) ABR Based on Location | Target Joints | 1.13 Bleeds per year | Standard Deviation 4.026 |
| FVIII Prophylaxis | Total (Treated and Untreated) ABR Based on Location | Soft Tissue/Muscle/Other | 1.55 Bleeds per year | Standard Deviation 3.346 |
| PF-07055480 | Total (Treated and Untreated) ABR Based on Location | All Joints | 0.51 Bleeds per year | Standard Deviation 2.819 |
| PF-07055480 | Total (Treated and Untreated) ABR Based on Location | Target Joints | 0.02 Bleeds per year | Standard Deviation 0.13 |
| PF-07055480 | Total (Treated and Untreated) ABR Based on Location | Soft Tissue/Muscle/Other | 0.76 Bleeds per year | Standard Deviation 4.303 |
Secondary
Total (Treated and Untreated) ABR Based on Location by Cumulative Follow-up Interval
Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) into which repeated bleeds occurred (3 or more spontaneous bleeds into a single joint within a consecutive 6month period). Target joint was considered resolved when there were =\<2 bleed into the joint within a 12-month period. Joint bleed: A bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of the following: pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. Muscle bleed: an episode of bleeding into a muscle, determined clinically and/or by imaging studies, generally associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hrs of sign and symptom of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total (Treated and Untreated) ABR Based on Location Yearly
Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleed into a single joint within 6 month). Joint bleed: bleeding episode by rapid loss of range of motion compared with baseline, associated with pain or an unusual sensation in the joint, swelling. Muscle bleed: bleeding episode into a muscle, determined by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hrs of sign and symptom of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Total (Treated and Untreated) ABR Yearly
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR
Treated bleed was defined as an event which necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. In this outcome measure treated ABR following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. Treated ABR for FVIII prophylaxis= \[(Number of treated bleeding episodes during pre-infusion period)\*365.25\]/ \[(Number of days of follow-up in pre-infusion period)\]. Treated ABR for PF-07055480: \[(Number of treated bleeding episodes during post-infusion period)\*365.25\] / \[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\].
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FVIII Prophylaxis | Treated ABR | 4.08 Treated bleeds per year |
| PF-07055480 | Treated ABR | 0.07 Treated bleeds per year |
Comparison: A repeated measures GLM was used with bleeds as dependent variable in negative binomial distribution, an interaction of duration by treatment, and 'participant' as random and treatment \& duration of follow-up as fixed effect.p-value: <0.000195% CI: [-5.57, -2.45]Repeated measures GLM
Secondary
Treated ABR Based on Cause
Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissues) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic procedure were not counted as bleeds. Treated: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Treated ABR for FVIII prophylaxis= \[(Number of treated bleeding episodes during pre-infusion period)\*365.25\]/ (Number of days of follow-up in pre-infusion period). Treated ABR for PF-07055480: \[(Number of treated bleeding episodes during post-infusion period)\*365.25\] /\[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\]. This outcome measure compared data collected from lead-in study C0371004 and from current study C3731003.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FVIII Prophylaxis | Treated ABR Based on Cause | Spontaneous | 2.81 Bleeds per year | Standard Deviation 4.469 |
| FVIII Prophylaxis | Treated ABR Based on Cause | Traumatic | 1.27 Bleeds per year | Standard Deviation 3.27 |
| PF-07055480 | Treated ABR Based on Cause | Spontaneous | 0.02 Bleeds per year | Standard Deviation 0.119 |
| PF-07055480 | Treated ABR Based on Cause | Traumatic | 0.07 Bleeds per year | Standard Deviation 0.213 |
Secondary
Treated ABR Based on Cause by Cumulative Follow-up Interval
Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR Based on Cause Yearly
Bleeds based on cause were spontaneous (bleeding for no apparent/known reason particularly into the joint, muscles and soft tissue) and traumatic (bleeding event occurring for an apparent/known reason). Bleeds related to a procedure/surgery such as hematomas/bruising which resulted from any surgeries or invasive procedures, or invasive diagnostic were not counted as bleeds. Treated bleed: necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR Based on Location
Target joint:major joint(hip,elbow,wrist,shoulder,knee,and ankle)with repeated bleeds(3 or more spontaneous bleeds into a single joint within 6month).Joint bleed:bleeding episode characterized by rapid loss of range of motion as compared with baseline,associated with pain or an unusual sensation in the joint,palpable swelling,and warmth of the skin over the joint.Muscle:bleeding episode into a muscle,determined clinically and/or by imaging study,associated with pain and/or swelling and functional impairment.Treated:necessitated administration of coagulation factor within72 hrs of sign or symptom of bleeding.FVIII prophylaxis=\[(Number of treated bleeding episodes during pre-infusion)\*365.25\]/(Number of days of follow-up in pre-infusion).PF-07055480:\[(Number of treated bleeding episodes during post-infusion)\*365.25\]/\[(last date of post-infusion-date of PF-07055480 infusion)-77days+1\].This outcome measure compared data collected from lead-in studyC0371004 and from current studyC3731003.
Time frame: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Population: Efficacy analysis population included all participants in the 'Dosed' population \[enrolled and received the study intervention\] who completed at least 6 months of follow up in the lead-in study and at least 15 months of follow-up or discontinued from the study C3731003 prior to the data cutoff for reporting. Data within the same participants were compared between Pre and Post infusion (2 groups described below), with different specified periods/durations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FVIII Prophylaxis | Treated ABR Based on Location | All Joints | 2.81 Bleeds per year | Standard Deviation 4.449 |
| FVIII Prophylaxis | Treated ABR Based on Location | Target Joints | 0.88 Bleeds per year | Standard Deviation 2.905 |
| FVIII Prophylaxis | Treated ABR Based on Location | Soft Tissue/Muscle/Other | 1.34 Bleeds per year | Standard Deviation 2.985 |
| PF-07055480 | Treated ABR Based on Location | All Joints | 0.06 Bleeds per year | Standard Deviation 0.205 |
| PF-07055480 | Treated ABR Based on Location | Target Joints | 0.00 Bleeds per year | Standard Deviation 0 |
| PF-07055480 | Treated ABR Based on Location | Soft Tissue/Muscle/Other | 0.03 Bleeds per year | Standard Deviation 0.136 |
Secondary
Treated ABR Based on Location by Cumulative Follow-up Interval
Target joint based on location: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleeds into a single joint within a consecutive 6-month period). Joint bleed: bleeding episode characterized by rapid loss of range of motion as compared with baseline, associated with pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. Muscle bleed: bleeding episode into a muscle, determined clinically and/or by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR Based on Location Yearly
Target joint: major joint (hip, elbow, wrist, shoulder, knee, and ankle) with repeated bleeds (3 or more spontaneous bleed into a single joint within 6 month). Joint bleed: bleeding episode by rapid loss of range of motion compared with baseline, associated with pain or an unusual sensation in the joint, swelling. Muscle bleed: bleeding episode into a muscle, determined by imaging study, associated with pain and/or swelling and functional impairment. Treated bleed: necessitated administration of coagulation factor within 72 hrs of sign or symptom of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR by Cumulative Follow-up Interval
Treated ABR: an event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion
Secondary
Treated ABR by Yearly
Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding.
Time frame: Maximum up to 5 years post PF-07055480 infusion