A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease

NCT04293185 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: HGB-210
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 9

Brief Summary

This is a non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using bb1111 (also known as LentiGlobin BB305 Drug Product for SCD).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• VOE-CR

  Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion

  6-18 months post-transplant

Secondary Outcomes (34)

• sVOE-CR

  6-18 months post-transplant

• Proportion of subjects achieving Globin Response

  6-24 months post-transplant

• Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent

  1-24 months post-transplant

• Change in the annualized number of severe VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent.

  1-24 months post-transplant

• VOE-CR24

  6-24 months post-transplant

Study Arms (1)

bb1111

EXPERIMENTAL

Subjects will receive treatment with a single dose of Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. Plerixafor mobilization and apheresis will also be used for collection of rescue cells.

Genetic: bb1111

Interventions

bb1111 GENETIC

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

Also known as: lovotibeglogene autotemcel, lovo-cel, LentiGlobin BB305 Drug Product for SCD, autologous CD34+ cell-enriched population from patients with SCD that contains HSCs transduced with BB305 LVV encoding the βA-T87Q-globin gene, suspended in cryopreservation solution

bb1111

Eligibility Criteria

• Age: 2 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
• Be ≥2 and ≤50 years of age at time of consent.
• Weigh a minimum of 6 kg.
• Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (\<16 years of age).
• Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
• In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
• Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
• Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
• Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).

You may not qualify if:

• Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
• Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity \>200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity \> 200 cm/sec (central read), a Screening MRA showing \> 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
• Clinically significant, active bacterial, viral, fungal, or parasitic infection
• Advanced liver disease, such as
• clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
• liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
• Inadequate bone marrow function, as defined by an absolute neutrophil count of \<1×10\^9/L (\<0.5×10\^9/L for subjects on hydroxyurea treatment) or a platelet count \<100×10\^9/L.
• Any contraindications to the use of 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.
• Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
• Unable to receive pRBC transfusion.
• Prior receipt of an allogeneic transplant.
• Prior receipt of gene therapy.
• Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
• Immediate family member with a known or suspected Familial Cancer Syndrome.

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (9)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University (VCU)

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

lyfgenia; Excipients

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Anjulika Chawla, MD, FAAP

  bluebird bio, Inc.

  STUDY DIRECTOR

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: February 12, 2020
• First Posted: March 3, 2020
• Study Start: February 14, 2020
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (9)