A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants

Plain-language summary

This study evaluated the safety and efficacy of autologous hematopoietic stem cell transplantation using the LentiGlobin BB305 Drug Product in people with β-thalassemia major. The product consists of the patient's own CD34+ stem cells modified with the LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene. This non-randomized, open-label, single-dose Phase 1/2 trial enrolled up to 18 participants aged 12 to 35 (including at least 3 adolescents) who required regular transfusions (at least 100 mL/kg of packed red blood cells per year or 8 or more transfusions per year).

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

Genetix Biotherapeutics Inc.

Intervention

LentiGlobin BB305 Drug Product

Start date

8/1/2013

Estimated completion

2/21/2018

Countries

United States, Australia, Thailand

Related genes

Locations

• Los Angeles, United States
• Oakland, United States
• Chicago, United States
• Philadelphia, United States
• Sydney, Australia
• Bangkok, Thailand

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion criteria:

* Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
* Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years.
* Eligible for allogeneic bone marrow transplant.
* Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion criteria:

* Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
* A white blood cell (WBC) count \<3 × 10\^9/L, and / or platelet count \<100 × 10\^9/L if not due to hypersplenism.
* Uncorrected bleeding disorder.
* Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.
* Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis).
* Receipt of an allogeneic transplant.
* Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value \>3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
* Kidney disease with a calculated creatinine clearance \<30% normal value.
* Uncontrolled seizure disorder.
* Diffusion capacity of carbon monoxide (DLco) \<50% of predicted (corrected for hemoglobin).
* A cardiac T2\* \<10 ms by magnetic resonance imaging (MRI).
* Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
* Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
* Participation in another clinical study with an investigational drug within 30 days of Screening.
* Any prior or current malignancy or myeloproliferative disorder.
* Prior receipt of gene therapy.