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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Participants <= 50 years of age at the time of consent or assent (as applicable), and
able to provide written consent (adults, or legal guardians, as applicable) or assent
(adolescents or children). Provided that the Data Monitoring Committee (DMC) has
approved enrolling participants younger than 5 years of age, participants younger than
5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are
reasonably anticipated to be able to provide at least the minimum number of cells
required to initiate the manufacturing process.
- Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year
(mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be
managed under standard thalassemia guidelines with >= 8 transfusions of pRBCs per year
in the 2 years preceding enrollment (participants >= 12 years).
- Clinically stable and eligible to undergo (HSCT).
- Treated and followed for at least the past 2 years in a specialized center that
maintained detailed medical records, including transfusion history.
Exclusion Criteria:
- Presence of a mutation characterized as ß0 mutation at both alleles of the ß-globin
gene (HBB) gene.
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2),
hepatitis B virus (HBV), or hepatitis C (HCV).
- A white blood cell (WBC) count less than (<) 3×10^9/Liter (L), and/or platelet count <
100×10^9/L not related to hypersplenism.
- Uncorrected bleeding disorder.
- Any prior or current malignancy.
- Immediate family member with a known Familial Cancer Syndrome.
- Prior HSCT.
- Advanced liver disease.
- A cardiac T2* < 10 ms by MRI.
- Any other evidence of severe iron overload that, in the Investigator's opinion,
warrants exclusion.
- Participation in another clinical study with an investigational drug within 30 days of
Screening.
- Any other condition that would render the participant ineligible for HSCT, as
determined by the attending transplant physician or investigator.
- Prior receipt of gene therapy.
- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception
for fertile participant.
- A known and available Human leukocyte antigen (HLA) matched family donor.
- Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and
plerixafor during the mobilization of hematopoietic stem cells and any
contraindications to the use of busulfan and any other medicinal products required
during the myeloablative conditioning, including hypersensitivity to the active
substances or to any of the excipients.
Age minimum:
N/A
Age maximum:
50 Years
Gender:
All
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Secondary Outcome(s)
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Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score
[Time Frame: Baseline, Month 12 and 24]
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Average Weighted Hemoglobin (Hb) During Transfusion Independence (TI)
[Time Frame: From 12 to 24 months post-transplant]
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Proportion of Participants with At least 50%, 60%, 75%, 90% or 100% Reduction in the Annualized pRBCs Transfusion
[Time Frame: From 12 to 24 months post-transplant]
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Weighted Average Nadir Hemoglobin (Hb)
[Time Frame: From 12 to 24 months post-transplant]
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Proportion of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion
[Time Frame: From 6 to 24 months]
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Annualized Volume of pRBC Transfusions
[Time Frame: From 12 to 24 months post-transplant]
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Change From Baseline in Cardiac T2 on MRI
[Time Frame: Baseline, Month 12 and 24]
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Change From Baseline in Serum Ferritin
[Time Frame: Baseline, Month 12 and 24]
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Proportion of Participants who Meet the Definition of Transfusion Independence (TI) at Month 24
[Time Frame: At Month 24 post-transplant]
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Time From Drug Product Infusion to Last pRBC Transfusion
[Time Frame: Up to 24 months post-transplant]
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Time From Last pRBC Transfusion to the Month 24
[Time Frame: Up to 24 months post-transplant]
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Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL)
[Time Frame: At Month 6, 9, 12, 18 and 24]
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Change From Baseline in EuroQol-5D (Youth version) (EQ-5D-Y)
[Time Frame: Baseline, Month 12 and 24]
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Duration of Transfusion Independence (TI)
[Time Frame: Up to 24 months post-transplant]
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Proportion of Participants Using Therapeutic Phlebotomy and Annualized Frequency of Phlebotomy
[Time Frame: Up to 24 months]
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Annualized Number of pRBC Transfusions
[Time Frame: From 12 to 24 months post-transplant]
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Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score
[Time Frame: Baseline, Month 12 and 24]
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Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI)
[Time Frame: Baseline, Month 12 and 24]
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Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2
[Time Frame: Baseline, Month 12 and 24]
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Unsupported Total Hb Levels Over Time
[Time Frame: At Month 6, 9, 12, 18 and 24]
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Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)
[Time Frame: Up to 24 months post-transplant]
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Change From Baseline in EuroQol-5D (EQ-5D)
[Time Frame: Baseline, Month 12 and 24]
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Time from Last Iron Chelation Use to Last Follow-up
[Time Frame: Up to 24 months]
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