Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (AFFINE)

Phase 3, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of PF-07055480 (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in Adult Male Participants With Moderately Severe to Severe Hemophilia A(FVIII:C≤1%)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Brazil
  • Campina, Brazil, 13083-970
    • Universidade Estadual de Campina
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre - Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital - Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8L 8E7
      • Hamilton Health Sciences Corporation
• France
  • Paris, France, 75015
    • Hopital Necker
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain
  • Frankfurt am Main, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universitaet, Medizinische Klinik II
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Hippokration"
  • Attikí
    • Athens, Attikí, Greece, 115 27
      • General Hospital of Athens ''Laiko''
• Italy
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi SODc Malattie Emorragiche e della Coagulazione
  • Naples, Italy, 80131
    • Dip. di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II - UOC di Medicina
  • RM
    • Roma, RM, Italy, 00161
      • Università degli studi di Roma "La Sapienza"- Policlinico Umberto I
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital - Transfusion Medicine
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital & Research Center
• South Korea
  • Seoul, South Korea, 05278
    • Kyung Hee University Hospital at Gangdong
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Valladolid, Spain, 47012
    • H.U. Rio Hortega
• Sweden
  • Skåne County
    • Malmö, Skåne County, Sweden, 205 02
      • Skåne University Hospital
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Adana Acibadem Hospital
  • Gaziantep, Turkey (Türkiye), 27310
    • Gaziantep University Sahinbey Research and Training Hospital
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical Faculty
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical Faculty, Pediatric Hematology
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's and St. Thomas' NHS Foundation Trust
• United States
  • California
    • Mountain View, California, United States, 94040
      • NOW Physical Therapy
    • Oakland, California, United States, 94607
      • Regents of The University of California
    • Palo Alto, California, United States, 94304
      • Clinical and Translational Research Unit (CTRU)
    • Palo Alto, California, United States, 94304
      • Lucile Packard Childrens Hospital
    • Redwood City, California, United States, 94063
      • The Board of Trustees of the Leland Stanford Junior University
    • Redwood City, California, United States, 94063
      • Imaging Clinic at Stanford Medicine Outpatient Center in Redwood City
    • San Francisco, California, United States, 94143
      • University of California, San Francisco - Clinical Research Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco - Outpatient Hematology Clinic
    • San Francisco, California, United States, 94143
      • UCSF IDS Pharmacy
    • San Francisco, California, United States, 94143
      • University of California, San Francisco - Moffitt/Long Inpatient Hematology
    • San Francisco, California, United States, 94115
      • UCSF Outpatient Radiology.
    • San Francisco, California, United States, 94143
      • UCSF lnvestigational Drug Service
    • San Francisco, California, United States, 94143
      • UCSF Outpatient Radiology (alternate location)
    • San Francisco, California, United States, 94143
      • UCSF Outpatient Radiology
    • San Jose, California, United States, 95131
      • Access Sourcecorp Deliverex (off-site storage)
    • Stanford, California, United States, 94305
      • Stanford Health Care
    • Stanford, California, United States, 94305
      • Stanford Health Care (hospital and IDS pharmacy)
  • Washington
    • Seattle, Washington, United States, 98101
      • Washington Institute for Coagulation
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Translational Research Unit (TRU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07055480 (giroctocogene fitelparvovec); Single administration of PF-07055480	Biological: PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy; Single IV infusion; Other Names: Gene Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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].	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	At 15 months following infusion of PF-07055480
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].	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 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.	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)
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).	Week 12 through Month 15 following PF-07055480 Infusion
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.	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)
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.	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 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.	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)
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.	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 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.	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)
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.	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)
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.	At Weeks 24, 52, 65 and 104
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.	Baseline (before infusion on Day 1); Weeks 24 and 52
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.	Baseline (before infusion on Day 1); Weeks 12, 24 and 52
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.	Baseline (before infusion on Day 1); Weeks 12, 24 and 52
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.	Maximum up to 5 years post PF-07055480 infusion
FVIII Activity Levels Yearly	FVIII activity levels will be assessed using one stage assay and chromogenic assay in the central lab.	Maximum up to 5 years post PF-07055480 infusion
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).	Maximum up to 5 years post PF-07055480 infusion
Annualized FVIII Consumption Yearly	Annualized FVIII consumption will be reported in IU/kg and total units (in IU).	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
Treated ABR by Yearly	Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
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.	Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
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.	Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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).	Maximum up to 5 years post PF-07055480 infusion
Annualized FVIII Consumption by Cumulative Follow-up Interval	Annualized FVIII consumption will be reported in IU/kg and total units (in IU).	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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.	From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months)
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.	From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months)
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.	Maximum up to 5 years post PF-07055480 infusion
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.	Maximum up to 5 years post PF-07055480 infusion
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).	Maximum up to 5 years post PF-07055480 infusion

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): June 17, 2024
• Study Completion (Estimated): October 25, 2026

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; AAV; Factor VIII; Hemophilia; PF-07055480; SB-525; FVIII; AAV6; Annualized bleeding rate; ABR; giroctocogene fitelparvovec; AFFINE
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Investigative Techniques; Therapeutics; Biological Therapy; Genetic Techniques; Genetic Engineering; Genetic Therapy
• Other Study ID Numbers: C3731003; 2024-512075-12-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No