A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia

NCT03207009 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: HGB-212
• Study Type: interventional
• Target: 19
• Locations: 6 countries
• Sites: 9

Brief Summary

This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (\<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. 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 Have Achieved 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 12 to 24 months post-transplant

Secondary Outcomes (25)

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

  At Month 24 post-transplant

• Duration of Transfusion Independence (TI)

  From start of TI up to Month 24 (actual maximum time frame of up to approximately 25 months due to visit window)

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

  From drug product infusion to start of TI (up to Month 24 [actual maximum time frame of up to approximately 25 months due to visit window])

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

  Timeframe varied by subject. For a given subject, the endpoint was calculated from 60 days after the last pRBC transfusion (so transfused blood did not confound the weighted average calculation) through the Month 24 Visit for that subject.

• Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR)

  From 12 to 24 months post-transplant

Study Arms (1)

LentiGlobin BB305 Drug Product

EXPERIMENTAL

LentiGlobin BB305 Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human βA-T87Q-globin)

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 less than or equal to (\<=) 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 other then β0 (e.g., β+, βE, βC) on at least one β-globin gene (HBB) allele.
• 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.
• 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 (9)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hopital d'enfants de la Timone

Marseille, 13385, France

Location

Hannover Medical School

Hanover, 30625, Germany

Location

University of Heidelberg

Heidelberg, 69120, Germany

Location

General Hospital of Thessaloniki 'G.Papanikolaou'

Thessaloniki, Greece

Location

IRCCS Ospedale Pediatrico Babino Gesu

Rome, Italy

Location

University College London Hospital

London, United Kingdom

Location

Related Publications (1)

• Kwiatkowski JL, Walters MC, Hongeng S, Yannaki E, Kulozik AE, Kunz JB, Sauer MG, Thrasher AJ, Thuret I, Lal A, Tao G, Ali S, Thakar HL, Elliot H, Lodaya A, Lee J, Colvin RA, Locatelli F, Thompson AA. Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype beta-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial. Lancet. 2024 Nov 30;404(10468):2175-2186. doi: 10.1016/S0140-6736(24)01884-1. Epub 2024 Nov 8.

  PMID: 39527960 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

Limitations and Caveats

Limitations of the trial such as small numbers of participants analysed or technical problems leading to unreliable data.

Results Point of Contact

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

clinicaltrials@bluebirdbio.com

+1-833-999-6378

Study Officials

• Himal L 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: June 29, 2017
• First Posted: July 2, 2017
• Study Start: June 8, 2017
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2022
• Last Updated: March 7, 2024
• Results First Posted: December 29, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

US (3); IT (1); FR (1); GR (1); GB (1); DE (2)