GIROCTOCOGENE FITELPARVOVEC for Hemophilia A|Moderately severe to severe hemophilia A

Inclusion criteria

• {"criterion_text":"- Males who have been followed on routine Factor VIII prophylaxis therapy in the lead-in study (C0371004) and have ≥ 150 documented exposure days to a Factor VIII protein product\n- Moderately severe to severe hemophilia A (Factor VIII activity ≤ 1%)\n- Suspension of FVIII prophylaxis therapy post study drug infusion"}

Exclusion criteria

• {"criterion_text":"- Anti-AAV6 neutralizing antibodies\n- History of inhibitor to Factor VIII\n- Laboratory values at screening visit that are abnormal or outside acceptable study limits\n- Significant and/or unstable liver disease, biliary disease, significant liver fibrosis\n- Planned surgical procedure requiring Factor VIII surgical prophylactic factor treatment 12 months from screening visit\n- Active hepatitis B or C\n- Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with either Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 or viral load >20 copies/mL"}

Primary endpoints

• {"endpoint_text":"- Total annualized bleeding rate (ABR, spontaneous and traumatic bleedings, treated and untreated) from Week 12 through at least 15 months following PF-07055480 infusion versus Total ABR on prior Factor VIII (FVIII) prophylaxis replacement regimen.","definition_or_measurement_approach":"ABR (total annualized bleeding rate) measured from Week 12 through at least 15 months after PF-07055480 infusion; compared against the participant's Total ABR on prior FVIII prophylaxis replacement regimen."}

Secondary endpoints

• {"endpoint_text":"- Factor VIII (FVIII) activity level >5% at 15 months following infusion of PF-07055480.","definition_or_measurement_approach":"FVIII activity measured at 15 months post-infusion; endpoint is proportion of participants with FVIII activity >5%."}
• {"endpoint_text":"- ABR (spontaneous and traumatic treated bleedings) from Week 12 through at least 15 months following PF-07055480 infusion versus ABR on prior FVIII prophylaxis replacement regimen.","definition_or_measurement_approach":"Annualized bleeding rate for spontaneous and traumatic treated bleedings measured from Week 12 through ≥15 months post-infusion, compared with ABR on prior FVIII prophylaxis."}
• {"endpoint_text":"- Annualized infusion rate (AIR) of exogenous FVIII from Week 12 through at least 15 months following infusion of PF-07055480 versus AIR on prior FVIII prophylaxis replacement regimen.","definition_or_measurement_approach":"AIR (annualized infusion rate) of exogenous FVIII measured from Week 12 through ≥15 months post-infusion; compared with prior regimen AIR."}
• {"endpoint_text":"- FVIII activity level from Week 12 through 15 months following infusion of PF-07055480.","definition_or_measurement_approach":"Serial measurements of FVIII activity levels from Week 12 through 15 months post-infusion."}
• {"endpoint_text":"- The following secondary parameters will be assessed from Week 12 through at least 15 months after PF-07055480 infusion and compared with prior FVIII prophylaxis replacement regimen: • Annualized FVIII consumption. • Annualized bleeding rate (ABR) of specific type: o by cause (spontaneous or traumatic) o by location (in joints, in target joints, or in soft tissue). • Total ABR by cause and by location. • Percentage of participants without bleeds.","definition_or_measurement_approach":"Assess annualized FVIII consumption, ABR by cause and location, total ABR, and percentage of participants without bleeds from Week 12 through ≥15 months and compare to prior FVIII prophylaxis regimen."}
• {"endpoint_text":"- The following secondary parameters will be assessed by visit after PF- 07055480 infusion: • FVIII activity level. • Change from baseline in joint health as measured by the HJHS instrument. • Change from baseline in the following patient-reported outcome (PRO) endpoints: o Haemophilia Quality of Life Questionnaire for Adults (Haem-AQoL) o Haemophilia Activities List (HAL).","definition_or_measurement_approach":"By-visit assessment of FVIII activity, change in joint health using HJHS, and change in PROs (Haem-A-QoL, HAL) from baseline."}
• {"endpoint_text":"- The following parameters will be analysed yearly or by visit as appropriate: • ABR. • FVIII activity level. • AIR of exogenous FVIII. • Annualized FVIII consumption. • ABR of specific type: o by cause (spontaneous or traumatic). o by location (in joint, in target joints, or in soft tissue). • Total ABR. • Total ABR by cause and by location. • Percentage of participants without bleeds.","definition_or_measurement_approach":"Annual or by-visit analyses of ABR, FVIII activity, AIR, annualized consumption, ABR by cause/location, total ABR, and percentage without bleeds across the study period."}
• {"endpoint_text":"- The following parameters will be analysed yearly or by visit as appropriate: • Change from baseline in joint health as measured by the HJHS instrument. • Change from baseline in PRO endpoints: Haem-A-QoL and HAL. In addition, ABR, Total ABR, and AIR will be analyzed throughout the 5 year study period.","definition_or_measurement_approach":"Yearly or by-visit analyses of changes from baseline in joint health (HJHS) and PROs (Haem-A-QoL, HAL); ABR, total ABR, and AIR analyzed across 5 years."}
• {"endpoint_text":"- Incidence and severity of adverse events (AEs). - Events of special interest (such as hypersensitivity reactions, clinically reported thrombotic events, and malignancy).","definition_or_measurement_approach":"Safety monitoring: capture incidence and severity of AEs and predefined events of special interest throughout study duration."}
• {"endpoint_text":"- Immunogenicity: • Antibodies against adeno-associated virus 6 (AAV6) capsid protein (neutralizing antibodies [nAbs] and anti-drug antibodies [ADAs]). • T-cell responses against AAV6 capsid and against the transgene. • FVIII inhibitors.","definition_or_measurement_approach":"Assessment of humoral (nAbs, ADAs) and cellular (T-cell) immune responses to AAV6 capsid and transgene, and monitoring for FVIII inhibitors."}

France

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

02-07-2024

Processing Time Days

40

Number Of Sites

1

Number Of Participants

12

Germany

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

14-06-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

1

Greece

Earliest CTIS Part Ii Submission Date

23-07-2024

Latest Decision Or Authorization Date

28-08-2024

Processing Time Days

36

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

13-06-2024

Processing Time Days

21

Number Of Sites

1

Number Of Participants

1

Sweden

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

18-06-2024

Processing Time Days

26

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pharmaron (Exton) Lab Services LLC

Responsibilities

vector detection by quantitative PCR in PBMC, saliva, semen, plasma, urine

Name

QPS LLC

Name

Covance Central Laboratory Services Inc.

Name

Monogram Biosciences Inc.

Name

Signant Health LLC

Responsibilities

Electronic Clinical Outcome Assessment (eCOA) provider (patient ediaries and site tablets)

Name

Parexel International Romania S.R.L.

Responsibilities

Clinical Logistic Services (IMP I/E licences, ancillary equipment, supplies project management)

Third parties

• {"country":"United States","full_name":"Pharmaron (Exton) Lab Services LLC","duties_or_roles":"vector detection by quantitative PCR in PBMC, saliva, semen, plasma, urine","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Covance Central Laboratory Services Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Monogram Biosciences Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"Electronic Clinical Outcome Assessment (eCOA) provider (patient ediaries and site tablets)","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Parexel International Romania S.R.L.","duties_or_roles":"Clinical Logistic Services (IMP I/E licences, ancillary equipment, supplies project management)","organisation_type":"Pharmaceutical company"}