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): 76
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Brazil
  • SAO Paulo
    • Campinas, SAO Paulo, Brazil, 13083-878
      • Centro de Hematologia e Hemoterapia de Campinas - Hemocentro UNICAMP
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre - Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital - Hamilton Health Sciences
• France
  • Paris, France, 75015
    • Hôpital 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 "LAIKO", 2nd Regional Blood Transfusion Center
  • Athens, Greece, 11527
    • General Hospital of Athens "Hippokration"
• Italy
  • Firenze, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi SODc Malattie Emorragiche e della Coagulazione
  • Napoli, 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
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital - Transfusion Medicine
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 05278
    • Kyung Hee University Hospital at Gangdong
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital & Research Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Valladolid, Spain, 47012
    • H.U. Rio Hortega
• Sweden
  • Skane
    • Malmö, Skane, Sweden, 205 02
      • Skåne University Hospital
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Adana, Turkey, 01130
    • Adana Acibadem Hospital
  • Gaziantep, Turkey, 27310
    • Gaziantep University Sahinbey Research and Training Hospital
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
  • Izmir, Turkey, 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
    • 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
      • 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
    • Stanford, California, United States, 94305
      • Stanford Health Care
  • 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	Time Frame
Total annualized bleeding rate (ABR)	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FVIII activity levels		15 months
Annualized bleeding rate (ABR)		15 months
Annualized infusion rate (AIR) of exogenous Factor VIII Activity		15 months
Annualized FVIII consumption		15 months
Annualized bleeding rate (ABR) and total ABR of specific type by cause and by location		15 months
Incidence and severity of AEs		5-year study period
Change in joint health using HJHS (Hemophilia Joint Health Score)	HJHS is a validated outcome tool developed for the assessment of joint health in people with hemophilia. The ordinal joint score assesses 9 items in 6 index joints.	Yearly up to 5 years
Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL)	HAL is a disease specific measure of the impact of hemophilia on functional abilities in adults. The instrument consists of 42 items across 7 domains, utilizing a past month recall period. Each item is rated on a scale of 0-6 with higher recoded scores indicating more functional limitations.	Yearly up to 5 years
Patient Reported Outcome (PRO) instrument - Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL)	Haem-A-QoL is a disease specific measure of health-related quality of life in patients with hemophilia. Intended for adults, the instrument uses a 4-week recall period to assess health across 10 domains consisting of 46 items. Each item is rated on a scale of 0-6 with lower scores indicating better health-related quality of life.	Yearly up to 5 years

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 (Estimated): June 17, 2024
• Study Completion (Estimated): October 25, 2028

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): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

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: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: C3731003; 2019-004451-37 (EudraCT Number)

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