A

Phase 1

• Conditions: This study will enroll subjects with transfusion dependent beta-thalassemia, who do not have beta0/beta0 genotype, defined by a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) or = 8 transfusions of pRBCs per year in the 2 years preceding enrollment.; MedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2015-004122-33-GB
• Lead Sponsor: bluebird bio, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-04-05
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

1. Subjects =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). Pediatric subjects (<12 years of age) may only be enrolled at a given site if approved by the relevant regulatory authority. Provided that the DMC has approved enrolling subjects younger than 5 years of age, subjects younger than 5 years of age may be enrolled at sites with regulatory approval for the specified age range if they weigh a minimum of 6 kg and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.
2. Diagnosis of TDT with a history of at least 100 mL/kg/year of pRBCs in the 2 years preceding enrollment (all subjects), or be managed under standard thalassemia guidelines (e.g.,Thalassemia International Federation) with =8 transfusions of pRBCs per year in the 2 years preceding enrollment.
3. Clinically stable and eligible to undergo HSCT.
4. Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records on RBC transfusions, in-patient hospitalization, and iron chelation history.
Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Presence of a mutation characterized as beta0 on both HBB alleles. For the purpose of this study, the HBB mutation IVS I-110 (G -> A) will be considered equivalent to a beta0 mutation
2. Positive for presence of HIV-1 or HIV-2, HBV, or HCV
3. Clinically significant and active bacterial, viral, fungal, or parasitic infection
4. A WBC count < 3 × 10^9/L, and/or platelet count < 100 × 10^9/L not related to hypersplenism
5. Uncorrected bleeding disorder
6. Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
7. Immediate family member with a known Familial Cancer Syndrome
8. Prior HSCT
9. Advanced liver disease
10. Baseline estimated glomerular filtration rate < 70 mL/min/1.73 m^2
11. Uncontrolled seizure disorder
12. Diffusion capacity of carbon monoxide (DLco) < 50% of predicted. If DLco cannot be assessed due to age or cognition-related restrictions, there must be a normal respiratory exam, chest radiograph without pulmonary infiltrates, and oxygen saturation by pulse oximetry >92% on room air. In the presence of clinically significant abnormal findings on chest radiograph, clinically significant abnormal findings on the respiratory exam, or oxygen saturation by pulse oximetry =92% on room air, the subject will be excluded.
13. A cardiac T2* < 10 ms by MRI
14. Any other evidence of severe iron overload that warrants exclusion
15. Participation in another clinical study with an investigational drug within 30 days of Screening
16. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator
17. Prior receipt of gene therapy
18. Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study
19. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects
20. An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol
21. A known and available HLA-matched family donor
22. Any contraindications to use of G-CSF and plerifaxor during the mobilization of hematopoietic stem cells and any contraindications to use of busulfan and any other medicinal products required during the myeloablative conditioning.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of treatment with LentiGlobin BB305 Drug Product in subjects =50 of age with transfusion-dependent beta-thalassemia, who do not have a beta0/beta0 genotype. ;Secondary Objective: To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects =50 of age with transfusion-dependent beta-thalassemia, who do not have a beta0/beta0 genotype. ;Primary end point(s): EFFICACY ENDPOINT<br>- The proportion of subjects who meet the definition of transfusion independence” (TI). TI is defined as a weighted average Hb =9 g/dL without any pRBC transfusions for a continuous period of =12 months at any time during the study after drug product infusion.;Timepoint(s) of evaluation of this end point: 24 months