Long-term Follow-up of Subjects With Sickle Cell Disease Treated With Ex Vivo Gene Therapy

Study Overview
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Brief Summary
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This is a multi-center, long-term safety and efficacy follow-up study for subjects with sickle cell disease who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored clinical studies. After completing the parent clinical study (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in the study.

Official Title
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Long-term Follow-up of Subjects With Sickle Cell Disease Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Other: Safety and efficacy assessments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s) Treated with drug product for therapy of sickle cell disease in a bluebird bio-sponsored clinical study Exclusion Criteria: There are no exclusion criteria for this study

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 53 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Subjects with sickle-cell disease<br>Subjects treated with ex vivo gene therapy drug product for sickle cell disease in a bluebird bio-sponsored study who agree to participate in this long-term follow-up study | Other: Safety and efficacy assessments<br>* Safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with immune-related AEs (e.g., autoimmune disorders, GVHD, opportunistic infections, HIV) |  | Through 15 years post-drug product infusion | 
| Number of subjects with new or worsening hematologic disorders |  | Through 15 years post-drug product infusion | 
| Number of subjects with new or worsening neurologic disorders |  | Through 15 years post-drug product infusion | 
| Number of subjects with malignancies |  | Through 15 years post-drug product infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with complete resolution of severe VOEs (sVOE-CR) over time through Year 15 |  | Through 15 years post-drug product infusion | 
| Proportion of subjects with complete resolution of VOEs (VOE-CR) over time through Year 15 |  | Through 15 years post-drug product infusion | 
| Annualized number of severe VOEs over time through Year 15 |  | Through 15 years post-drug product infusion | 
| Annualized number of VOEs over time through Year 15 |  | Through 15 years post-drug product infusion | 
| Change from parent study baseline in annualized number of severe VOEs over time through Year 15 |  | Through 15 years post-drug product infusion | 
| Assessment of total Hb over time post-drug product infusion through Year 15 |  | Through 15 years post-drug product infusion | 
| Assessment of non-transfused total Hb over time post-drug product infusion through Year 15 | Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q | Through 15 years post-drug product infusion | 
| Assessment of HbS percentage of non-transfused total Hb over time post-drug product infusion through Year 15 | Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q | Through 15 years post-drug product infusion | 
| Assessment of HbAT87Q percentage of non-transfused total Hb over time post-drug product infusion through Year 15 | Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q | Through 15 years post-drug product infusion | 
| Assessment of non-HbS percentage of non-transfused total Hb over time post-drug product infusion through Year 15 | Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q. Non-HbS is the total g/dL of HbF + HbA2 + HbAT87Q | Through 15 years post-drug product infusion | 
| Change from parent study baseline through Year 15 in hemolysis markers |  | Through 15 years post-drug product infusion | 
| Change from parent study baseline through Year 15 in markers of iron stores |  | 15 years post-drug product infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cells