Investigation Into the Use of BAH243 Lentiviral Vector for Gene Therapy in Treating Sickle Cell Disease

NCT06399107 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202493
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, non-randomized, single-dose Phase 1/2 trial involving around 85 adult and pediatric participants aged between 2 and 50 years with sickle cell disease (SCD). It aims to assess the effectiveness of hematopoietic stem cell transplantation (HSCT) using BAH243 for SCD.

Conditions

Sickle Cell Disease; Sickle-Cell Disease With Crisis

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 (2)

• sVOE-CR

  6-18 months post-transplant

• The proportion of subjects achieving Globin Response

  6-24 months post-transplant

Study Arms (1)

Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy)

EXPERIMENTAL

Participants will be administered a one-time dose of the Drug Product, created using their own CD34+ hematopoietic stem cells which are gathered through plerixafor-induced mobilization and apheresis. These cells are then modified with the BAH243 lentiviral vector (LVV), which carries the human beta-A-T87Q globin gene. Additionally, the same process of plerixafor mobilization and apheresis will be employed to collect rescue cells.

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

Interventions

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

An autologous CD34+ cell-enriched population from patients with sickle cell disease (SCD), which includes hematopoietic stem cells (HSCs) that have been transduced with the BAH243 lentiviral vector (LVV) carrying the βA-T87Q-globin gene, is preserved in a cryopreservation solution.

Also known as: BAH243

Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy)

Eligibility Criteria

• Age: 2 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises

Interventions

Busulfan

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

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

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 3, 2024
• Study Start: August 1, 2024
• Primary Completion: November 10, 2025
• Study Completion: December 28, 2025
• Last Updated: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)