This clinical trial aims to test a new gene therapy in adults (18 to 35 years old) with beta thalassemia who require regular red cell transfusions. The study will evaluate the safety and efficacy of genetically engineered blood stem cells using a novel lentiviral vector that produces a high levels of a healthy beta globin. Several tests and procedures such as review of medical history, blood and urine tests, bone marrow aspirate/biopsy, heart ultrasound, electrocardiogram, magnetic resonance imaging (MRI) of the heart and liver, and lung tests will be done to find out if subjects are eligible to participate in this trial. If eligible, blood stem cells will be collected by apheresis. These stem cells will then have a healthy beta globin gene inserted. Subjects will then be hospitalized, and chemotherapy will be given to empty out the bone marrow. The stem cells, with the inserted gene (CHOP-ALS20), will then be given back to the subject. Subjects will be followed for side effects and to see if the inserted gene helps make hemoglobin and reduce or stop blood transfusions.

This clinical trial study uses a modified adeno-associated virus (AAV) to carry the human factor VIII gene to the liver. In the liver is where factor VIII protein is made. The study product, SPK-8011, is available only to participants in this research study. This product has not been approved yet for use in the general public. This will be the first hemophilia A gene transfer research study done in the United States. To learn more about the benefits and risks related to this study, please contact Dr. Lindsey George at (267) 425-0132. In order to participate in this study, you must be male, 18 years or older, have hemophilia A with FVIII activity levels less or equal to 2%, a history of bleeding that requires prophylaxis or on demand therapy, and no history of inhibitor to factor VIII. This study requires a number of visits over the course of 12 months. All costs related to participation in the study will either be covered or reimbursed by the Sponsor of the study, Spark Therapeutics, and participants will be compensated for their time.