Phase 3, open label, single arm study to evaluate efficacy and safety of FIX gene transfer with PF-06838435 (rAAV Spark100-hFIX-Padua) in adult male participants with moderately severe to severe hemophilia B (FIX:C =2%)

Not Applicable

Conditions: Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Registration Number: KCT0008736

Lead Sponsor: Kyung Hee University Hospital at Gangdong

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot yet recruiting

Sex: Male

Target Recruitment: 3

Inclusion Criteria

1.Participants must have completed at least 6 months of routine FIX prophylaxis therapy during the lead in study (C0371004) prior to providing consent at the screening visit for this study.
2.Participants who have documented moderately severe to severe hemophilia B, defined as FIX:C ≤2%.
3.Participants must agree to suspend prophylaxis therapy for hemophilia B after administration of the IP. FIX replacement therapy is allowed as needed (see Section 6.5.1).
4.Acceptable screening laboratory values as follows:
•Hemoglobin ≥11 g/dL;
•Platelets ≥100,000 cells/µL;
•Creatinine ≤2.0 mg/dL.
Sex
5.Male.
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Male participants are eligible to participate if they agree to the following for at least 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:
•Agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person
Informed Consent
6.Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

1.Anti AAV Spark100 neutralizing antibodies (nAb) titer ≥1:1 (ie, positive for nAb), performed by a central laboratory during screening.
2.Prior history of inhibitor to FIX or positive inhibitor testing as measured by the central laboratory ≥0.6 Bethesda Units (BU) during screening. Clinical signs or symptoms of decreased response to FIX.
3.Known hypersensitivity to FIX replacement product or intravenous immunoglobulin administration.
4.History of chronic infection or other chronic disease that investigator deems as an unacceptable risk.
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.Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) >2 × upper limit of normal (ULN), based on central laboratory results.
7.Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN 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 FIX surgical prophylactic factor treatment in the next 15 months.
11.Participants using therapies that are restricted. See Section 6.5.2 for therapies not allowed during study participation.
Prior/Concurrent Clinical Study Experience
12.Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within the last 12 weeks, excluding participation in Study C0371004.
Diagnostic Assessments
13.Active hepatitis B or C; HBsAg, HBV DNA positivity, or HCV RNA positivity.
14.Significant liver disease, as 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* or AST to Platelet Ratio Index (APRI) >1. In the investigator’s opinion, if there is concern regarding the FibroTest results due to a confounding medical history (eg, proteinuria can impact FibroTest result), the investigator can perform a different assessment of liver fibrosis (eg, FibroScan or APRI) during the screening period.
*Please note: if a participan

Study & Design

Study Type: Interventional Study

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
on inferiority on annualized bleeding rate (ABR) for total bleeds (treated and untreated) from Week 12 to Month 15 versus standard of care (SOC) FIX prophylaxis replacement regimen, comparing pre-and post-IP infusion.

Secondary Outcome Measures

Name	Time	Method
on-inferiority on ABR for treated bleeds from Week 12 to Month 15 versus SOC FIX prophylaxis replacement regimen, comparing pre- and post-IP infusion.