Clinical trial NCT04370054: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults
Official title: 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%)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia A
Keywords: PF-07055480
SB-525
Hemophilia
Factor VIII
FVIII
Gene Therapy
AAV
AAV6
Annualized bleeding rate
ABR
giroctocogene fitelparvovec
AFFINE
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-04-30
Enrollment: 76
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Total annualized bleeding rate (ABR)
timeFrame: 15 months
Secondary outcomes:
measure: FVIII activity levels
timeFrame: 15 months
measure: Annualized bleeding rate (ABR)
timeFrame: 15 months
measure: Annualized infusion rate (AIR) of exogenous Factor VIII Activity
timeFrame: 15 months
measure: Annualized FVIII consumption
timeFrame: 15 months
measure: Annualized bleeding rate (ABR) and total ABR of specific type by cause and by location
timeFrame: 15 months
measure: Change in joint health using HJHS (Hemophilia Joint Health Score)
timeFrame: Yearly up to 5 years
measure: Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL)
timeFrame: Yearly up to 5 years
measure: Patient Reported Outcome (PRO) instrument - Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL)
timeFrame: Yearly up to 5 years
measure: Incidence and severity of AEs
timeFrame: 5-year study period
Other outcomes:
Locations:
city: Mountain View
country: United States
facility: NOW Physical Therapy
state: California
city: Palo Alto
country: United States
facility: Clinical and Translational Research Unit (CTRU)
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Childrens Hospital
state: California
city: Redwood City
country: United States
facility: Imaging Clinic at Stanford Medicine Outpatient Center in Redwood City
state: California
city: San Francisco
country: United States
facility: UCSF IDS Pharmacy
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Clinical Research Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Moffitt/Long Inpatient Hematology
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Outpatient Hematology Clinic
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Seattle
country: United States
facility: Washington Institute for Coagulation
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Translational Research Unit (TRU)
state: Washington
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Campinas
country: Brazil
facility: Centro de Hematologia e Hemoterapia de Campinas - Hemocentro UNICAMP
state: SAO Paulo
city: Hamilton
country: Canada
facility: McMaster University Medical Centre - Hamilton Health Sciences
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital - Hamilton Health Sciences
state: Ontario
city: Paris
country: France
facility: Hopital Necker
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet, Medizinische Klinik II
city: Athens
country: Greece
facility: General Hospital of Athens ''Laiko''
state: Attikí
city: Athens
country: Greece
facility: General Hospital of Athens "Hippokration"
city: Roma
country: Italy
facility: Università degli studi di Roma "La Sapienza"- Policlinico Umberto I
state: RM
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi SODc Malattie Emorragiche e della Coagulazione
city: Napoli
country: Italy
facility: Dip. di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II - UOC di Medicina
city: Nagoya
country: Japan
facility: Nagoya University Hospital - Transfusion Medicine
state: Aichi
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
state: Saitama
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Valladolid
country: Spain
facility: H.U. Rio Hortega
city: Malmö
country: Sweden
facility: Skåne University Hospital
state: Skane
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Adana
country: Turkey
facility: Adana Acibadem Hospital
city: Gaziantep
country: Turkey
facility: Gaziantep University Sahinbey Research and Training Hospital
city: Izmir
country: Turkey
facility: Ege University Medical Faculty, Pediatric Hematology
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: