Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B

Evaluation of the long-term level of persistence and potential late or delayed adverse events associated with PF-06838435 (formerly SPK-9001), assessment of the durability of the transgene expression, and determination of the effects of PF-06838435 on clinical outcomes in individuals who have previously received a single administration of PF-06838435 in the C0371005 study. Amendment 2 of this study incorporates a dose-escalation substudy to evaluate the safety, tolerability, and kinetics of a single IV infusion of PF-06838435 at a higher dose than that used in the C0371005 study. The dose-escalation participants will also be followed for long-term safety and efficacy.

This study is currently only enrolling into the dose-escalation substudy with subsequent long-term follow-up. The Eligibility Criteria for entry into the dose-escalation substudy is presented below:

Inclusion criteria

• Able to provide informed consent and comply with requirements of the study
• Males age 18 to 65 years with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
• Received ≥50 exposure days to factor IX products
• No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
• Agree to refrain from donating sperm and either abstain from intercourse or use reliable barrier contraception until 3 consecutive semen samples are negative for vector sequences

Exclusion criteria

• Evidence of active hepatitis B or C
• Currently on antiviral therapy for hepatitis B or C
• Have significant underlying liver disease
• Serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
• Neutralizing antibody titers to the capsid portion of PF-06838435 above the established threshold
• Sensitivity to heparin or heparin induced thrombocytopenia; sensitivity to any of the study interventions, or components thereof, or drug or other allergy
• Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 3 months of screening visit
• Any concurrent clinically significant major disease or condition
• Unable or unwilling to comply with the study procedures