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

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ClinicalTrials.gov Identifier: NCT01745120
Recruitment Status : Completed
First Posted : December 7, 2012
Last Update Posted : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
bluebird bio

December 6, 2012
December 7, 2012
March 30, 2018
August 2013
February 8, 2018   (Final data collection date for primary outcome measure)
  • 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 ]
  • 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 ]
Production of greater than or equal to 2.0 g/dL of HbA containing betaA-T87Q globin for the 6-mon time period between M 18 - M 24 post-transplant [ Time Frame: M 18 - M 24 post-transplant ]
Change in hemoglobin production following treatment with LentiGlobin BB305 Drug Product
Complete list of historical versions of study NCT01745120 on ClinicalTrials.gov Archive Site
  • Hematopoietic stem cell engraftment [ Time Frame: 42 days post-transplant ]
  • 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 ]
Not Provided
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A Study Evaluating the Safety and Efficacy of the LentiGlobin® BB305 Drug Product in Beta-Thalassemia Major Subjects
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)
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].
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.
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Beta-thalassemia Major
Genetic: LentiGlobin® BB305 Drug Product
Transplant of autologous hematopoietic stem cells transduced with LentiGlobin® BB305 lentiviral vector.
Experimental: LentiGlobin® BB305 Drug Product
Intervention: Genetic: LentiGlobin® BB305 Drug Product
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
15
February 21, 2018
February 8, 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
12 Years to 35 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Thailand,   United States
 
 
NCT01745120
HGB-204
Yes
Not Provided
Not Provided
bluebird bio
bluebird bio
Not Provided
Study Director: Mohammed Asmal, MD bluebird bio
bluebird bio
March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP