A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral β-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product)
Phase: PHASE1
Conditions: Beta-Thalassemia Major, Sickle Cell Disease
Sponsor: Genetix Biotherapeutics Inc.

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INTRODUCTION .............................................................................................................. 19 
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STUDY OBJECTIVES AND ENDPOINTS .................................................................... 28 
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STUDY ASSESSMENTS ................................................................................................... 46 
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REFERENCES ................................................................................................................... 72 
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Treatment Discontinuation and Enrollment Suspension Criteria 
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Stopping Rules for Individual Subjects for Busulfan IV Conditioning 
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Individual Subject Stopping Rules 
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Subject Exclusion Criteria 
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Subject Identification and Registration 
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4.5
Subject Withdrawal from the Study 
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5
STUDY TREATMENTS 
5.1
Description of LentiGlobin BB305 Lentiviral Vector and LentiGlobin 
BB305 Drug Product 
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5.2
Summary of Treatments to be Performed or Administered 
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Table 5-1 
Cell Source, Usage, and Minimum Dose of LentiGlobin BB305 Drug 
Product or Rescue for E-ThalM and SCD 
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5.2.1
Mobilization and Apheresis Procedure (for E-ThalM Subjects) 
5.2.1.1
Mobilization 
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FULVLV
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EHDGDSWHGLI:%&LV!î/(TXDOO\DPHDVXUHPHQWRI&'FHOOVLQSHULSKHUDOEORRG
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LQFOXGLQJDGYHUVHHYHQWVDVVRFLDWHGZLWKHDFKDJHQW
5.2.1.2
Apheresis Procedure 
$SKHUHVLVLVWREHSHUIRUPHGIRUVXEMHFWVZLWKȕ7KDO0RQO\
3%0&VZLOOEHFROOHFWHGSHU623DWWKHFOLQLFDOVLWH7KHJRDOLVWRFROOHFWDWRWDORIDWOHDVW
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5.2.2
Bone Marrow Harvest Procedure (All SCD Subjects and Some 
β-ThalM Subjects) 
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SURFHGXUHVWKH\ZLOOXQGHUJRDERQHPDUURZKDUYHVWXQGHUJHQHUDODQHVWKHVLD6XEMHFWVZLWK
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WKH+E6FRQWHQWEHORZDQGWREULQJWKH+EOHYHOWRaJG/
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5.2.3
Drug Product Manufacturing Process 
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5.2.4
Conditioning 
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5.2.4.1
Rationale for the Use of Busulfan IV for Conditioning 
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DOPRVWSXUHO\P\HORDEODWLYHDVLWLQGXFHVYHU\OLWWOHLPPXQRVXSSUHVVLRQ/XFDUHOOLHWDO
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5.2.5
Infusion Procedures 
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5.3
Storage and Stability 
5.3.1
LentiGlobin BB305 Lentiviral Vector 
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LentiGlobin BB305 Drug Product 
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Blinding and Breaking the Blind 
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5.5.2
LentiGlobin BB305 Lentiviral Vector Packaging, Labeling, Shipment, 
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LentiGlobin BB305 Drug Product Packaging and Labeling 
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Duration of Subject Participation 
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Product Accountability 
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LentiGlobin BB305 Drug Product 
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Prior and Concomitant Treatment 
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Concomitant Treatments during Conditioning 
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STUDY ASSESSMENTS 
6.1
Schedule of Events 
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Testing for Replication Competent Lentivirus (RCL) 
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Proviral Integration Site Analysis in Blood and Bone Marrow by 
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6.3.16.2
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Procedures for SAE Reporting 
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6.3.18
Pregnancy 
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6.3.19
Unscheduled Visits 
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6.3.20
Long-Term Follow-Up Protocol 
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6.4
Appropriateness of Measurements 
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7
STATISTICAL PROCEDURES 
7.1
Sample Size Estimation 
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7.2
Populations for Analysis 
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7.3
Procedures for Handling Missing, Unused, and Spurious Data 
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7.4
Statistical Methods 
7.4.1
General Methods 
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7.4.2
Disposition of Subjects 
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7.4.3
Demographic and Baseline Characteristics 
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7.5
Efficacy Analysis 
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7.5.1
For All Subjects 
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7.5.2
For SCD Subjects 
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7.6
Safety Analysis 
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Procedures for Reporting Deviations to Original Statistical Analysis 
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ADMINISTRATIVE AND REGULATORY REQUIREMENTS 
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Ethical Considerations 
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Comité de Surveillance 
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Subject Information and Informed Consent 
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Subject Confidentiality 
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Protocol Compliance 
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Direct Access to Source Data 
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Case Report Form Completion 
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8.8
Record Retention 
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Liability and Insurance 
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Publication of Study Findings and Use of Information 
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8.10.1
Publications 
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Presentations 
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REFERENCES 
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