A Study Evaluating the Safety and Efficacy of the LentiGlobin® BB305 Drug Product in Beta-Thalassemia Major Subjects

Study Description

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Brief Summary:

This is a non-randomized, open label, multi-site, single-dose, Phase 1/2 study in up to 18 subjects (including at least 3 adolescents between 12 and 17 years of age, inclusive) with beta-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin® BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin® BB305 Lentiviral Vector encoding the human βA-T87Q-globin gene].

Condition or disease	Intervention/treatment	Phase
Beta-thalassemia Major	Genetic: LentiGlobin® BB305 Drug Product	Phase 1; Phase 2

Detailed Description:

Subject participation for this study will be 2 years. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	18 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product)
Study Start Date :	August 2013
Actual Primary Completion Date :	February 8, 2018
Actual Study Completion Date :	February 21, 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: LentiGlobin® BB305 Drug Product	Genetic: LentiGlobin® BB305 Drug Product; Transplant of autologous hematopoietic stem cells transduced with LentiGlobin® BB305 lentiviral vector.

Outcome Measures

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Primary Outcome Measures :

1. Evaluate the efficacy of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the production of hemoglobin containing the therapeutic globin protein [βA-T87Q-globin] [ Time Frame: 18 - 24 months post-transplant ]
2. Evaluate the safety of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the incidence of adverse events [ Time Frame: 0-24 months post-transplant ]

Secondary Outcome Measures :

1. Hematopoietic stem cell engraftment [ Time Frame: 42 days post-transplant ]
2. Assess transgene marking as determined by measurement of the average vector copy number in peripheral blood and bone marrow [ Time Frame: 0 - 24 months post-transplant ]

Eligibility Criteria

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Ages Eligible for Study:	12 Years to 35 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

• Subjects 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 × 109/L, and / or platelet count <100 × 109/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.

Contacts and Locations

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Locations

United States, California
Oakland, California, United States
United States, Illinois
Chicago, Illinois, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Australia
Sydney, Australia
Thailand
Bangkok, Thailand

Sponsors and Collaborators

bluebird bio

Investigators

Study Director:	Mohammed Asmal, MD	bluebird bio

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarré C, Beuzard Y, Chrétien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.

Responsible Party:	bluebird bio
ClinicalTrials.gov Identifier:	NCT01745120 History of Changes
Other Study ID Numbers:	HGB-204
First Posted:	December 7, 2012
Last Update Posted:	March 30, 2018
Last Verified:	March 2018

Keywords provided by bluebird bio:

gene therapy; beta thalassemia; hemoglobin; anemia; CD34

Additional relevant MeSH terms:

Thalassemia; beta-Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic	Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn