FVIII GTx Hem A Phase 3 Study

Not Applicable

Conditions: Congenital malformations, deformations and chromosomal abnormalities

Registration Number: KCT0005828

Lead Sponsor: Pfizer Pharmacueticals Korea

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot yet recruiting

Sex: Male

Target Recruitment: 63

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age:
1. Participant must be =18 and <65 years of age at the time of signing the informed consent.
Type of Participant and Disease Characteristics:
2. Participants must have completed at least 6 months of routine FVIII prophylaxis therapy during the lead-in study (C0371004) at the start of the screening period and have =150 documented exposure days to a FVIII protein product (standard half-life or extended half-life recombinant, plasma derived).
3. Participants who have documented moderately severe to severe hemophilia A defined as circulating FVIII activity levels =1%.
4. Participants must agree to suspend prophylaxis therapy for hemophilia A after administration of the study intervention. FVIII replacement therapy is allowed as needed.
5. Acceptable screening central laboratory values as follows:
•Hemoglobin =11 g/dL
•Platelets =100,000 cells/µL;
•Creatinine =2.0 mg/dL.
Sex
6. Male
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a. Male Participants:
Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time required for 3 consecutive ejaculate samples to test negative for vector shedding:
• Refrain from donating sperm.
PLUS, either:
• Be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
OR
• Must agree to use contraception/barrier as detailed below.
o Agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
Informed Consent
7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Anti-AAV6 nAb titers, above or equal to the established threshold of 1:4, performed by a central laboratory during screening.
2. Prior history of FVIII inhibitor (clinical or laboratory-based assessment) defined as a titer =0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the ULN for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FVIII administration.
3. Known hypersensitivity to FVIII replacement product or intravenous immunoglobulin administration.
4. History of chronic infection or other chronic disease that investigator deems an unacceptable risk. Any participant with a history of thrombotic events including but not limited to stroke or myocardial infarction.
5. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation or other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior (including alcoholism) or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
6. ALT, AST, ALP >2x ULN, based on central laboratory results.
7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), based on central laboratory results.
8. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones), is acceptable if the participant otherwise meets entry criteria.
Note: Participants who have a central laboratory test value that is outside the range specified by the exclusion criteria may have the test repeated, by the central laboratory, to determine eligibility; however, the result must be available prior to Baseline Visit/Visit 2.
Prior/Concomitant Therapy:
9. Currently on antiviral therapy for hepatitis B or C.
10. Any participant with a planned surgical procedure requiring FVIII surgical prophylactic factor treatment in the next 12 months.
11. Participants using therapies that are restricted.
12. Participants who previously received PF-07055480 or any other gene therapy.
Prior/Concurrent Clinical Study Experience:
13. Previously dosed in a gene therapy research trial at any time or an interventional clinical study within the last 12 weeks, excluding participation in Study C0371004.
Diagnostic Assessments:
14. Active hepatitis B or C:
• HBcAb, HBsAg, and HBV DNA positivity. Exception: if a participant is positive for HBcAb, then HBsAg and HBV DNA must be negative for inclusion.
• HCV-RNA positivity.
15. Significant liver disease, defined by pre-existing diagnosis of portal hypertension, splenomegaly or hepatic encephalopathy. Additionally, during screening, a serum albumin level below normal limits and/or significant liver fibrosis by any of the following diagnostic modalities: FibroScan score >8 kPa units, Fibro Test/FibroSURE >0.48. In the investigator’s opinion, if th

Study & Design

Study Type: Interventional Study

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ABR (spontaneous and traumatic bleedings) through 12 months following PF 07055480 infusion (from Week 3) versus ABR on prior FVIII prophylaxis replacement regimen.

Secondary Outcome Measures