- Males ≥ 18 and documented FIX activity (≤2%) within the last 12 months prior to baseline visit.
- Willing and able to comply with scheduled visits, FIX prophylaxis treatment plan,
laboratory tests and other study procedures.
- Previous experience with FIX therapy (≥50 documented exposure days to a FIX protein
product such as recombinant, plasma-derived or extended half-life FIX product)
- Subjects as per usual care setting on FIX prophylaxis replacement therapy
(recombinant, plasma-derived or extended half-life FIX product) must have the
intention to remain on FIX prophylaxis replacement therapy for the duration of the
- No known hypersensitivity to FIX replacement product
- No history of FIX inhibitor (clinical or laboratory-based assessment) defined as a
titer ≥ to 0.6 BU/mL
- Anti-AAV-Spark100 neutralizing antibodies titer (above the lowest detectable titer)
performed by a central laboratory during screening.
- Lack of patient compliance with documentation of bleeds and/or FIX prophylaxis
replacement therapy administration.
- A subject is not eligible if either HbsAg is positive or HBV-DNA is
- A subject who is currently undergoing anti-viral therapy for hepatitis B is not
- A subject who is currently undergoing anti-viral therapy for chronic hepatitis C is
- A subject is not eligible if his HCV-RNA load assay result is positive/detectable.
- Currently on antiviral therapy for hepatitis B or C.
- A subject is not eligible if any of the following pre-existing diagnoses, which are
indicative of significant underlying liver disease, are present in the medical record:
- Portal hypertension; or
- Splenomegaly; or
- Hepatic encephalopathy
- A subject is not eligible if the serum albumin level is below the testing laboratory's
lower limit of normal; and
- At least one of the following diagnostic tests for liver fibrosis indicating ?
stage 3. The following results are indicative of fibrosis ? stage 3 and exclude
the subject from participation:
- FibroScan, with a score >8.3 kPa units;
- FibroTest/FibroSURE with a result >0.48; or
- AST-to-Platelet Ratio Index (APRI) >1.
- Documented serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with
Cluster of Differentiation 4 positive (CD4+) cell count ?200 mm3 within the last 12
months prior to screening.
- History of chronic infection or other chronic disease that the investigator deems an
unacceptable risk. Any patient with a history of thrombotic events including but not
limited to stroke or myocardial infarction. Any concurrent clinically significant
major disease or condition that the investigator deems unsuitable for participation.
- Participation in other studies involving investigational drug(s) within the last 3
months prior to study entry and/or during study participation or in a previous gene
therapy clinical study within the last 12 months prior to screening.
- Any subject with a planned surgical procedure requiring FIX surgical prophylactic
factor treatment in the next 24 months.