MedPath

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: 19.0Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2015-004122-33-IT
Lead Sponsor
bluebird bio, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
15
Inclusion Criteria

1. Subjects between 12 and 50 years of age, inclusive
2. Diagnosis of transfusion-dependent thalassemia (including severe HbE/beta-thalassemia), also known as beta-thalassemia major, with a history of at least 100 mL/kg/year of pRBCs or = 8 transfusions of pRBCs per year for the prior 2 years
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: 5
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 beta0 and be excluded
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
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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the efficacy of treatment with LentiGlobin BB305 Drug Product in subjects =12 and =50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype. ;Secondary Objective: To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects =12 and =50 of age with transfusion-dependent beta-thalassemia, who do not have beta0/beta0 genotype. ;Primary end point(s): EFFICACY ENDPOINT<br>- The proportion of subjects who meet the definition of transfusion independence” (TI). ;Timepoint(s) of evaluation of this end point: 24 months
Secondary Outcome Measures
NameTimeMethod
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