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

NCT01745120 | Completed Phase 1 Results DMC

• 1 other identifier: HGB-204
• Study Type: interventional
• Target: 19
• Locations: 3 countries
• Sites: 6

Brief Summary

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

Conditions

β-thalassemia Major

Keywords

gene therapy; β thalassemia; hemoglobin; anemia; CD34

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24

  Percentage of participants with sustained production of \>=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months (Month 18 to Month 24) was reported.

  Month 18 to Month 24

• Percentage of Participants Who Achieved Transfusion Independence (TI)

  TI was defined as a weighted average hemoglobin (Hb) \>= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of \>=12 months at any time during the study after LentiGlobin BB305 Drug Product infusion. Percentage of participants who achieved TI from time of drug product infusion up to 24 months was reported.

  From time of drug product infusion up to 24 months

Secondary Outcomes (17)

• Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24

  Month 18, Month 24

• Duration of Transfusion Independence (TI)

  From time of drug product infusion up to 24 months

• Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI)

  From time of drug product infusion up to 24 months

• Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI)

  From time of drug product infusion up to 24 months

• Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)

  From time of drug product infusion up to 24 months

Study Arms (1)

LentiGlobin BB305 Drug Product

EXPERIMENTAL

Genetic: LentiGlobin BB305 Drug Product

Interventions

LentiGlobin BB305 Drug Product GENETIC

Transplant of autologous hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector.

LentiGlobin BB305 Drug Product

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (6)

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Sydney, Australia

Location

Unknown Facility

Bangkok, Thailand

Location

Related Publications (1)

• 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, Pondarre C, Beuzard Y, Chretien 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 beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.

  PMID: 29669226 DERIVED

MeSH Terms

Conditions

Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Medical Director
• Organization: bluebird bio, Inc.

medinfo@bluebirdbio.com

339-499-9300

Study Officials

• Mohammed Asmal, MD

  Genetix Biotherapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 7, 2012
• Study Start: August 1, 2013
• Primary Completion: February 8, 2018
• Study Completion: February 21, 2018
• Last Updated: May 8, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-04

Locations

US (4); AU (1); TH (1)