The study compared the differences between the trial drug before and after infusion, and evaluated the non-inferiority of the annual average bleeding rate (ABR) of total bleeding events (treatment-free and treatment-free) from week 12 to month 15 compared with standard of care (SOC) FIX prophylactic alternative therapy.

The study compared the differences between the trial drug before and after infusion, and evaluated the non-inferiority of the annual average bleeding rate (ABR) of total bleeding events (treatment-free and treatment-free) from week 12 to month 15 compared with standard of care (SOC) FIX prophylactic alternative therapy.

injection

PF-06838435

270

1.00x10^13 vg/mL

The study compared the differences between the trial drug before and after infusion, and evaluated the non-inferiority of the annual average bleeding rate (ABR) of total bleeding events (treatment-free and treatment-free) from week 12 to month 15 compared with standard of care (SOC) FIX prophylactic alternative therapy.

Participants are eligible for this trial only if they meet all of the following criteria:

Participant Type and Disease Characteristics
1. Prior to providing consent at the screening follow-up visit for this trial, participants must have completed at least 6 months of prospective data collection based on general care during their introductory trial (C0371004) while receiving FIX prophylactic replacement therapy.

Note: The exact duration of FIX prophylactic replacement therapy for each individual participant may exceed 6 months, as this will be specified based on their inclusion in this trial (C0371002).

2. Participants with a documented moderate to severe hemophilia B, defined as FIX:C ≤2%.

3. Participants who have previously received FIX treatment (with documented exposure days ≥50 days for FIX protein products, such as recombinant, plasma-derived, or extended half-life FIX products).

4. Participants must agree to discontinue prophylactic treatment for hemophilia B after administration of the investigational drug. FIX replacement therapy may be administered as needed.

5. Acceptable screening laboratory values ​​are as follows:

• Heme ≥11 g/dL;

• Platelets ≥100,000 cells/μL;

• Creatinine ≤ 2.0 mg/dL.

Sex

6. Male.

Participants are eligible to participate in the trial if they agree to adhere to the following requirements starting from Day 1/3 return visit (IP infusion return visit) and continue until at least 3 consecutive ejaculation sample carrier exfoliation tests are negative:

• Avoid donating sperm.

In addition to one of the following:

• Abstain from heterosexual or homosexual sexual activity according to preference and usual lifestyle (long-term and continuous abstinence), and agree to maintain abstinence.

Alternatively

• Consent to use contraception/barriers is required, detailed below:

• Consent to use male condoms during activities that could transmit ejaculate to another person.

• The above-described method of contraception will continue to be used even if the participant's partner becomes pregnant before administration or at any time during the trial, until the participant has three consecutive negative ejaculation sample tests.

• The method of contraception used by the male should be consistent with local regulations regarding contraception for clinical trial participants.

Informed Consent

7. Able to provide signed informed consent as described in Appendix 1 of the trial protocol, including compliance with the Informed Consent Document (ICD) and the requirements and limitations listed in this trial protocol.

• For information on German trial sites, please refer to the German Appendix.

8. Participants must be between 18 years of age (or the national minimum age of consent if older than 18) and ≤65 years of age (inclusive) at the first follow-up visit (screening period).

Participants are ineligible to participate in the trial if they meet any of the following criteria:
Medical Conditions
1. Anti-AAV (Rh74var nAb) titer above the established threshold (i.e., nAb positive), as determined by the central laboratory during screening. nAb testing may be repeated if necessary. In such cases, a new sample must be collected for retesting.

2. A history of FIX inhibitory factors or a positive inhibitory factor test result during screening, measured by the central laboratory as ≥0.6 Bethesda units (BU). Clinical signs or symptoms of reduced response to FIX.

3. Known allergy to FIX alternatives or IV immunoglobulin.

4. A history of chronic infections or other chronic diseases, which the trial administrator deems an unacceptable risk.

5. Any participant with a condition associated with an increased risk of thromboembolism, such as a known hereditary or acquired predisposition to thrombosis, or a history of thrombotic events, including but not limited to: stroke, myocardial infarction, and/or venous thrombosis. 6. Any clinically significant or major illness or condition, or other acute or chronic medical or psychiatric illness, that the trial administrator deems unsuitable for participation in this trial, including recent (within the past year) or active suicidal ideation or behavior (including alcoholism), or abnormal laboratory test results that may increase the risk of participation or interfere with the interpretation of trial results, may, in the trial administrator's judgment, render the participant unsuitable for participation in this trial. Furthermore, any participant with a history of cancer requiring treatment (e.g., chemotherapy, radiation therapy, immunotherapy) (including malignant liver cancer) will be excluded, except for appropriately treated basal cell carcinoma or squamous cell carcinoma of the skin, or benign tumors that have been surgically removed and do not require chemotherapy, radiation therapy, and/or immunotherapy. Any other tumors that have been cured through resection should be discussed between the trial administrator and the trial sponsor.

7. Based on central laboratory test results, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) > 2 times the upper limit of normal (ULN);

8. Based on central laboratory test results, bilirubin > 1.5 times the ULN (sporadic bilirubin > 1.5 times the ULN is acceptable if bilirubin is isolated and direct bilirubin < 35%);

9. Based on the trial administrator's assessment, currently suffering from unstable liver or biliary tract disease, defined as having ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome and asymptomatic gallstones) is acceptable if the participant meets the inclusion criteria.

Previous/Concurrent Therapies

10. Currently receiving antiviral therapy for hepatitis B or C.

11. Any participant scheduled for a planned surgical procedure requiring FIX prophylactic factor therapy within the next 15 months.

12. Participants using restricted therapies. See Section 6.6.2 of the trial protocol for therapies not permitted during trial participation.

Previous/Concurrent Clinical Trial Experience

13. Use of medication at any time within the past 12 weeks in a previous gene therapy study or in an interventional therapy clinical trial, excluding participation in trial C0371004.

Diagnostic Assessment

14. Active hepatitis B or C; positive for hepatitis B surface antigen (HBsAg), HBV DNA, or HCV RNA.

15. Major liver disease, defined as a pre-existing diagnosis of portal hypertension, splenomegaly, or hepatic encephalopathy. Additionally, during screening, participants must have a serum albumin concentration below the normal limit and/or be diagnosed with significant liver fibrosis using one of the following diagnostic tools (note that only one test is required for screening purposes): FibroScan median stiffness score > 8 kPa units, or FibroTest/FibroSURE > 0.48*. FibroScan is preferred if applicable. If there are doubts about the results of FibroTest or FibroScan due to a history of interfering medical conditions (e.g., proteinuria can affect FibroTest results), or if there are conflicting results between the diagnostic tools, the trial administrator should contact the trial commissioner.

*Note: FibroTest cannot be used for fibrosis detection if the participant has a known history of Gilbert's syndrome. However, FibroScan can still be used to test the participant.

16. Serological evidence of HIV1 or HIV2 infection, CD4+ cell count ≤ 200 mm3 and/or viral load > 20 copies/mL. Participants with HIV are permitted if their CD4+ cell count is >200 mm3 and viral load is ≤20 copies/mL, and they maintain highly active antiretroviral therapy (HAART) throughout the trial. Note: HIV infection will be confirmed by a positive HIV antibody test and an HIV viral load >20 copies/mL. If the serology is positive, a negative viral load (≤20 copies/mL) in the absence of an HIV history and HAART treatment will be considered a false positive, and the patient will be eligible to participate in the trial.

Other Exclusion Criteria

17. Staff members of the trial site directly involved in the trial execution and their families, other staff members of the trial site supervised by the trial administrator, or participants who are Pfizer employees directly involved in the trial execution, including their families.

• For information on German trial sites, please refer to the German Appendix.

18. Participants who, in the opinion of the trial administrator, cannot adhere to scheduled follow-up visits, treatment plans (participants must agree to suspend prophylactic treatment for hemophilia B after the trial intervention), laboratory tests, and other trial procedures for up to six years after PF-06838435 infusion.

• For information on German trial sites, please refer to the German appendix.

19. Hypersensitivity to heparin or heparin-induced thrombocytopenia.

20. Participation in this trial is prohibited based on the advice of the trial administrator or the medical monitor of the trial sponsor.

• For information on Japanese trial sites, please refer to the Japanese appendix.

Note: Participants whose central laboratory test values ​​exceed the range specified for exclusion criteria may require repeat testing by the central laboratory to determine eligibility; however, results must be obtained before the baseline follow-up visit/second follow-up visit. For any questions regarding inclusion or exclusion criteria, please contact the medical team of the trial sponsor.