Lead-in Study to Collect Prospective Efficacy and Safety Data of Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Participants

Study Overview
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Brief Summary
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The aim of this prospective, observational study is to establish a dataset on the frequency of bleeding events, as well as other characteristics of bleeding events and FVIII infusions, in patients with clinically severe hemophilia A receiving prophylactic FVIII replacement therapy as standard of care. The data collected from this study may assist in providing baseline information for comparison to the Spark's investigational hemophilia A gene therapy in future Phase 3 studies.

Official Title
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A Multi-Center, Observational Study in Males With Hemophilia A

Conditions
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Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Hemophilia A, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Hematologic Diseases, Hemorrhagic Disorders, Factor VIII Deficiency

Intervention / Treatment
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* Drug: Standard of Care FVIII Replacement therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent. Males ≥18 years of age. Clinically severe hemophilia A Previous exposure to FVIII therapy No prior history of hypersensitivity or anaphylaxis associated with an FVIII or intravenous immunoglobulin administration. No measurable inhibitor against FVIII Willing to participate and receive treatment in a future Spark hemophilia A gene therapy study. Exclusion Criteria: Documented active hepatitis B or C within the past 12 months of Screening Currently on antiviral therapy to treat hepatitis B or C; Documented significant liver disease within the past 6 months of Screening Have serological evidence of HIV-1 or HIV-2 Anti-AAV-Spark 200 neutralizing titers ≥1:1 Previously received SPK-8011; Previously dosed with any investigational or approved gene therapy product at any time or treated with an investigational drug within the last 12 weeks; Planned surgical procedure in the next 12 months requiring FVIII prophylactic treatment. Any history of chronic infection or other chronic disease, concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) including active malignancy, except for non-melanoma skin cancer, any other condition or any other unspecified reasons that, in opinion of the Investigator or Sponsor, makes the participant unsuitable for participation and dosing in a future clinical study for Spark's hemophilia A gene therapy. Unable or unwilling to comply with the schedule of visits and/or study assessments described in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational Cohort<br>Adult males with clinically severe hemophilia A, who are negative for neutralizing antibody (NAb) to AAV-Spark200 | Drug: Standard of Care FVIII Replacement therapy<br>* There is no investigational product being administered. Subjects will be administering their own standard of care FVIII replacement therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of bleeding events, annualized | Annualized bleeding rate (ABR) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose and total FVIIII consumption | Total FVIII replacement therapy consumption and the corresponding dose | 12 months | 
| Annualized number of infusions (AIR) | Number of reported infusions over the study period | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor VIII, Factor VIII Protein, Recombinant