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

This study is currently recruiting participants.
Verified November 2013 by bluebird bio
Sponsor:
Information provided by (Responsible Party):
bluebird bio
ClinicalTrials.gov Identifier:
NCT01745120
First received: December 6, 2012
Last updated: November 11, 2013
Last verified: November 2013
  Purpose

This is a non randomized, open label, multi-site, single-dose, Phase 1/2 study in up to 15 adults 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 β-A(T87Q)-globin gene].


Condition Intervention Phase
Beta-thalassemia Major
Genetic: LentiGlobin® BB305 Drug Product
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 β-A(T87Q)-Globin Vector (LentiGlobin® BB305 Drug Product)

Resource links provided by NLM:


Further study details as provided by bluebird bio:

Primary Outcome Measures:
  • 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 [β-A(T87Q)-globin] [ Time Frame: 18 - 24 months post-transplant ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Hematopoietic stem cell engraftment [ Time Frame: 42 days post-transplant ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: August 2013
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LentiGlobin® BB305 Drug Product Genetic: LentiGlobin® BB305 Drug Product
Transplant of autologous hematopoietic stem cells transduced with LentiGlobin® BB305 lentiviral vector.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Adult subjects between 18 and 35 years of age, inclusive, at the time of consent, and able to provide written consent.
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01745120

Contacts
Contact: Alexandria Petrusich clinicaltrials@bluebirdbio.com

Locations
United States, California
Recruiting
Oakland, California, United States
United States, Illinois
Recruiting
Chicago, Illinois, United States
Sponsors and Collaborators
bluebird bio
Investigators
Study Director: Rob Ross, MD bluebird bio
  More Information

No publications provided

Responsible Party: bluebird bio
ClinicalTrials.gov Identifier: NCT01745120     History of Changes
Other Study ID Numbers: HGB-204
Study First Received: December 6, 2012
Last Updated: November 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by bluebird bio:
gene therapy
beta thalassemia
hemoglobin
anemia
CD34

Additional relevant MeSH terms:
Beta-Thalassemia
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 15, 2014