Long-Term Safety and Efficacy of Spark-Sponsored Gene Therapies in Males With Hemophilia A

Study Overview
=================
Brief Summary
-----------------
This long-term follow-up study will continue to evaluate the long-term safety and efficacy of SPK-8011 and SPK-8016 in males with hemophilia A, who have received a single intravenous administration of SPK-8011 or SPK-8016 in any Spark-sponsored SPK-8011 or SPK-8016 study.

Detailed Description
-----------------
This study will follow patients with hemophilia A, who have received a single intravenous administration of SPK-8011 or SPK-8016 in any prior Spark-sponsored SPK-8011 or SPK-8016 study. Subjects will be followed for up to a total of 5 years post infusion (including the time on the dosing study).

Official Title
-----------------
A Multi-Center Evaluation of the Long-Term Safety and Efficacy of Spark-sponsored Gene Therapies in Males With Hemophilia A

Conditions
-----------------
Hemophilia A

Intervention / Treatment
-----------------
* Genetic: SPK-8011


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: Have received a single intravenous administration of SPK-8011 or SPK-8016 in any Spark-sponsored gene therapy study; and Understand the purpose and risks of the study and provide signed and dated informed consent before undergoing any study-specific procedures. Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: 1.Unable or unwilling to comply with the schedule of visits and study assessments as described in this study protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: SPK-8011|Observational long-term safety follow-up study of subjects previously treated with SPK-8011 in any Spark-sponsored SPK-8011 study|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of FVIII Inhibitors | Incidence of FVIII Inhibitors | 4 years | 
| Incidence of all adverse events | Incidence of all adverse events | 4 years | 
| Incidence(s) of new or exacerbation of adverse events of interest | Such as: malignancies, neurologic, rheumatologic or other autoimmune, or hematologic disorders | 4 years | 
| Annual bleeding rate | Annual bleeding rate | 4 years | 
| FVIII activity levels | FVIII activity levels | 4 years | 
| Total FVIII consumption | Total FVIII consumption | 4 years | 
| Number of FVIII infusions | Number of FVIII infusions | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint Health Assessment | Assessment of joint health for six index joints using a modified Hemophilia Joint Health Score (HJHS). The HJHS is a physical examination assessment tool, that measures joint health in the domain of body structure and function (i.e. impairment), of the joints most commonly affected by bleeding in hemophilia: the knees, ankles, and elbows | 4 years | 
| Target Joint Assessment | Investigator assessment of bleeding in target joints (e.g., hip, elbow, wrist, shoulder, knee, and ankle) | 4 years | 
| Haem-A-QoL | Quality-of-life (QoL) assessment | 4 years | 
| EQ-5D-5L | Quality-of-life (QoL) assessment | 4 years | 
| Activities Assessments | Hemophilia Activities List | 4 years | 
| Health Economics Assessment | Collection of information including number of hospitalizations, emergency room visits, physician visits and work/school days missed | 4 years |