A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype

NCT02906202 | Completed Phase 3 Results DMC

• 1 other identifier: HGB-207
• Study Type: interventional
• Target: 24
• Locations: 6 countries
• Sites: 8

Brief Summary

This is a single-arm, multi-site, single-dose, Phase 3 study in 23 participants less than or equal to (\<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), also known as β-thalassemia major, who do not have a β0 mutation at both alleles of the hemoglobin β (HBB) gene. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.

Conditions

Beta-Thalassemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Meet the Definition of Transfusion Independence (TI)

  TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion.

  From 14 to 24 months post-transplant

Secondary Outcomes (24)

• Percentage of Participants Who Meet the Definition of Transfusion Independence (TI) at Month 24

  At Month 24 post-transplant

• Duration of Transfusion Independence (TI)

  From start of TI up to Month 24

• Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)

  From 14 months post-drug product infusion through Month 24

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

  From 60 days after the last pRBC transfusion through Month 24

• Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume

  12 months post-drug product infusion through Month 24

Study Arms (1)

LentiGlobin BB305 Drug Product

EXPERIMENTAL

Participants aged less than or equal to (\<=) 50 years received a single intravenous (IV) infusion of LentiGlobin BB305 Drug Product at a dose of greater than or equal to (\>=) 5.0\*10\^6 CD34 plus (+) cells per kilogram (cells/kg) following myeloablative conditioning with busulfan (termed the Transplant population).

Genetic: LentiGlobin BB305 Drug Product

Interventions

LentiGlobin BB305 Drug Product GENETIC

LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.

Also known as: betibeglogene autotemcel

LentiGlobin BB305 Drug Product

Eligibility Criteria

• Age: 0 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants \<= 50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Provided that the Data Monitoring Committee (DMC) has approved enrolling participants younger than 5 years of age, participants younger than 5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.
• Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year (mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be managed under standard thalassemia guidelines with \>= 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants \>= 12 years).
• Clinically stable and eligible to undergo (HSCT).
• 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:

• Presence of a mutation characterized as β0 mutation at both alleles of the β-globin gene HBB.
• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
• A white blood cell (WBC) count less than (\<) 3×10\^9/Liter (L), and/or platelet count \< 100×10\^9/L not related to hypersplenism.
• Uncorrected bleeding disorder.
• Any prior or current malignancy.
• Immediate family member with a known Familial Cancer Syndrome.
• Prior HSCT.
• Advanced liver disease.
• A cardiac T2\* \< 10 ms by MRI.
• Participation in another clinical study with an investigational drug within 30 days of Screening.
• Any other condition that would render the participant ineligible for HSCT, as determined by the attending transplant physician or investigator.
• Prior receipt of gene therapy.
• Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participant.
• A known and available Human leukocyte antigen (HLA) matched family donor.
• Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (8)

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Hanover, Germany

Location

Unknown Facility

Rome, Italy

Location

Unknown Facility

Bangkok, Thailand

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (2)

• Locatelli F, Thompson AA, Kwiatkowski JL, Porter JB, Thrasher AJ, Hongeng S, Sauer MG, Thuret I, Lal A, Algeri M, Schneiderman J, Olson TS, Carpenter B, Amrolia PJ, Anurathapan U, Schambach A, Chabannon C, Schmidt M, Labik I, Elliot H, Guo R, Asmal M, Colvin RA, Walters MC. Betibeglogene Autotemcel Gene Therapy for Non-beta0/beta0 Genotype beta-Thalassemia. N Engl J Med. 2022 Feb 3;386(5):415-427. doi: 10.1056/NEJMoa2113206. Epub 2021 Dec 11.

  PMID: 34891223 DERIVED

• Hamed EM, Meabed MH, Aly UF, Hussein RRS. Recent Progress in Gene Therapy and Other Targeted Therapeutic Approaches for Beta Thalassemia. Curr Drug Targets. 2019;20(16):1603-1623. doi: 10.2174/1389450120666190726155733.

  PMID: 31362654 DERIVED

MeSH Terms

Conditions

beta-Thalassemia

Interventions

betibeglogene autotemcel

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

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

medinfo@bluebirdbio.com

339-499-9300

Study Officials

• Himal Lal Thakar, MD

  Genetix Biotherapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 20, 2016
• Study Start: August 8, 2016
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: June 18, 2023
• Results First Posted: June 18, 2023

Record last verified: 2023-05

Locations

US (3); FR (1); IT (1); GB (1); TH (1); DE (1)