Global Epidemiologic Study of Preexisting Immunity to AAV in Adults With Severe Hemophilia

• Non-treatment, seroprevalence (Other): Non-treatment study examining the prevalence of preexisting immunity to adeno-associated virus (AAV)

Primary outcomes

• Prevalence of neutralizing antibodies (NAb) - Baseline visit [Baseline visit]: Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes
• Prevalence of neutralizing antibodies (NAb) - Year 1 Visit [Year 1 visit]: Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes
• Prevalence of neutralizing antibodies (NAb) - Year 2 Visit [Year 2 visit]: Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes
• Prevalence of neutralizing antibodies (NAb) - Year 3 Visit [Year 3 visit]: Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes

Secondary outcomes

• Prevalence of NAb to AAV including AAV2 and AAV8 [Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit]: Prevalence of neutralizing antibodies (NAb) to adeno-associated virus (AAV) including AAV2 and AAV8
• Prevalence of binding antibodies to AAV, including AAV8 and AAV2 [Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit]: Prevalence of binding antibodies to adeno-associated virus (AAV), including AAV8 and AAV2
• T-cell mediated immune response to AAV8 [Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit]: T-cell mediated immune response to AAV8

Sex: Male, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Participant is male between 18 and 75 years old at the time of screening.
2. Established severe hemophilia A (plasma Factor VIII (FVIII) activity <1%) or B (plasma Factor IX (FIX) activity ≤2%).
3. Provision of signed informed consent form (ICF).
4. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Bleeding disorder(s) other than hemophilia A or B.
2. Personal laboratory evidence of having developed inhibitors to FVIII or FIX protein at any time (≥0.6 Bethesda Units \[BU\] on any single test).
3. Currently receiving systemic immunosuppressive therapy, cytotoxic chemotherapy, immunoglobulin therapy, or monoclonal antibody therapy.
4. Received systemic antiviral and/or interferon therapy within 30 days of blood draw, with the exception of treatment for human immunodeficiency virus (HIV).
5. Currently receiving ribavirin and/or interferon based therapy for active hepatitis C virus (HCV).
6. Received immunoglobulin therapy or plasma infusion within 120 days of the blood draw.
7. Has a known immune deficiency other than HIV.
8. Has lymphocyte or plasma cell malignancies.
9. Participant is a family member or employee of the investigator.

• Study Director, Study director, Shire