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

Study Overview
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Brief Summary
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Assess the seroprevalence of neutralizing antibodies (NAb) to AAV in adults with severe hemophilia A (coagulation factor VIII [FVIII] <1%) or moderately severe to severe hemophilia B (coagulation factor IX [FIX] ≤2%).

Official Title
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A Global Epidemiologic Study to Determine the Prevalence of Neutralizing Antibodies and Related Adaptive Immune Responses to Adeno-Associated Virus (AAV) in Adults With Hemophilia

Conditions
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Hemophilia A, Hemophilia B

Intervention / Treatment
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* Other: Non-treatment, seroprevalence


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is male between 18 and 75 years old at the time of screening. Established severe hemophilia A (plasma Factor VIII (FVIII) activity <1%) or B (plasma Factor IX (FIX) activity ≤2%). Provision of signed informed consent form (ICF). Participant is willing and able to comply with the requirements of the protocol. Exclusion Criteria: Bleeding disorder(s) other than hemophilia A or B. Personal laboratory evidence of having developed inhibitors to FVIII or FIX protein at any time (≥0.6 Bethesda Units [BU] on any single test). Currently receiving systemic immunosuppressive therapy, cytotoxic chemotherapy, immunoglobulin therapy, or monoclonal antibody therapy. Received systemic antiviral and/or interferon therapy within 30 days of blood draw, with the exception of treatment for human immunodeficiency virus (HIV). Currently receiving ribavirin and/or interferon based therapy for active hepatitis C virus (HCV). Received immunoglobulin therapy or plasma infusion within 120 days of the blood draw. Has a known immune deficiency other than HIV. Has lymphocyte or plasma cell malignancies. Participant is a family member or employee of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hemophilia A<br>Participants with hemophilia A | Other: Non-treatment, seroprevalence<br>* Non-treatment study examining the prevalence of preexisting immunity to adeno-associated virus (AAV)<br>|
| Hemophilia B<br>Participants with hemophilia B | Other: Non-treatment, seroprevalence<br>* Non-treatment study examining the prevalence of preexisting immunity to adeno-associated virus (AAV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of neutralizing antibodies (NAb) - Baseline visit | Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes | Baseline visit | 
| Prevalence of neutralizing antibodies (NAb) - Year 1 Visit | Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes | Year 1 visit | 
| Prevalence of neutralizing antibodies (NAb) - Year 2 Visit | Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes | Year 2 visit | 
| Prevalence of neutralizing antibodies (NAb) - Year 3 Visit | Prevalence of NAb to naturally occurring adeno-associated virus (AAV) serotypes | Year 3 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of NAb to AAV including AAV2 and AAV8 | Prevalence of neutralizing antibodies (NAb) to adeno-associated virus (AAV) including AAV2 and AAV8 | Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit | 
| Prevalence of binding antibodies to AAV, including AAV8 and AAV2 | Prevalence of binding antibodies to adeno-associated virus (AAV), including AAV8 and AAV2 | Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit | 
| T-cell mediated immune response to AAV8 | T-cell mediated immune response to AAV8 | Baseline visit, Year 1 visit, Year 2 visit, and Year 3 visit |