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

NCT ID: NCT03207009

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-08
• Study Completion Date: 2022-11-15

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LentiGlobin BB305 Drug Product

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

Group Type: EXPERIMENTAL

LentiGlobin BB305 Drug Product

Intervention Type: GENETIC

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

Interventions

LentiGlobin BB305 Drug Product

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

Intervention Type: GENETIC

Other Intervention Names

betibeglogene autotemcel

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Any other evidence of severe iron overload that, in the investigator's opinion, warrants exclusion.
• 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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genetix Biotherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Himal L Thakar, MD

Role: STUDY_DIRECTOR

Genetix Biotherapeutics Inc.

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

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

Chicago, Illinois, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Hopital d'enfants de la Timone

Marseille, , France

Hannover Medical School

Hanover, , Germany

University of Heidelberg

Heidelberg, , Germany

General Hospital of Thessaloniki 'G.Papanikolaou'

Thessaloniki, , Greece

IRCCS Ospedale Pediatrico Babino Gesu

Rome, , Italy

University College London Hospital

London, , United Kingdom

Countries

United States; France; Germany; Greece; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39527960 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HGB-212

Identifier Type: -

Identifier Source: org_study_id