A

Phase 1

• Conditions: This study will enroll subjects with transfusion dependent beta-thalassemia, who have a 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: EUCTR2016-003611-35-IT
• Lead Sponsor: bluebird bio, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-05
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 15

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). Provided that the DMC has approved enrolling subjects younger than 5 years of age, subjects younger than 5 years of age may be enrolled 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, 2014) with =8 transfusions of pRBCs per year in the 2 years
preceding enrollment (subjects =12 years).
3. Clinically stable.
4. Treated and followed for at least the past 2 years in a specialized
center that maintained detailed medical records on RBC transfusions, inpatient hospitalization, and iron chelation history.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
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 other than beta0 (e.g., beta+, betaE, betaC) on at least one HBB allele. 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 as determined by the clinical investigator.
4. A white blood cell (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 (i.e. parent or siblings) 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
(corrected for Hb and/or alveolar volume, as clinically indicated).
13. A cardiac T2* <10 ms by MRI.
14. Any other evidence of severe iron overload that, in the investigator's opinion, 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 human leukocyte antigen (HLA)-matched family donor. If required by regional authority, patients with a known and available matched unrelated donor will be excluded from the study.
22. Any contraindications to the use of G-CSF and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products used during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

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 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 have a beta0/beta0 genotype.;Timepoint(s) of evaluation of this end point: 24 months;Primary end point(s): EFFICACY ENDPOINT<br>-The proportion of subjects who meet the definition of transfusion reduction (TR), defined as demonstration of a =60% reduction in volume of pRBC transfusion requirements (in mL/kg) in the posttreatment time period of Months 12 to 24, compared to the average annual transfusion requirements in the 24 months prior to study enrollment