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Purpose

The purpose of this study is to evaluate the efficacy and safety of Lenti-D Drug Product (also known as elivaldogene autotemcel or Skysona, hereafter referred to as eli-cel) after myeloablative conditioning with busulfan and fludarabine in participants with CALD. A participant's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the participant following myeloablative conditioning. Enrollment and treatment in Study ALD-104 have been completed and further enrollment in this study is not expected, although participants follow-up remains ongoing.

Condition

Eligibility

Eligible Ages
Under 17 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/independent ethics committee (IEC) approved consent. Informed assent will be sought from capable participants, in accordance with the directive of the IRB/IEC and with local requirements. 2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent. 3. Active CALD as defined by: 1. Elevated very long chain fatty acids (VLCFA) values, and 2. Active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii. GdE on MRI of demyelinating lesions. 4. NFS < or = 1.

Exclusion Criteria

  1. Prior receipt of an allogeneic transplant or gene therapy. 2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: participants must discontinue use of these medications at time of consent. 3. Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study. 4. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents). 5. Hematological compromise as evidenced by: 1. Peripheral blood absolute neutrophil count (ANC) count <1500 cells/ cubic millimeter (mm^3), and either 2. Platelet count <100,000 cells/mm^3, or 3. Hemoglobin <10 gram per deciliter (g/dL). 6. Hepatic compromise as evidenced by: 1. Aspartate transaminase (AST) value greater than (>) 2.5 × upper limit of normal (ULN) 2. Alanine transaminase (ALT) value >2.5 × ULN 3. Total bilirubin value >3.0 milligram per deciliter (mg/dL), except if there is a diagnosis of Gilbert's Syndrome and the participant is otherwise stable 7. Baseline estimated glomerular filtration rate <70 milliliter per minute (mL/min)/1.73 square meter (m^2). 8. Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%). 9. Immediate family member with a known or suspected Familial Cancer Syndrome. 10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection. 11. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B virus (HBV); hepatitis C virus (HCV); human T lymphotrophic virus 1 (HTLV-1). (Note that participants who have been vaccinated against HBV [positive for HBV surface antibodies] who are negative for other markers of prior HBV infection [e.g., negative for HBV core Ab] are eligible. Participants with past exposure to HBV [hepatitis B core antibody [HBcAb] -positive and/or hepatitis B e-antigen antibody [HBeAb]-positive] are also eligible for the study provided they have a negative test for HBV DNA. Also note that participants who are positive for anti-hepatitis C Ab are eligible as long as they have a negative hepatitis C viral load). 12. Any clinically significant cardiovascular, hematological, or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures. 13. Absence of adequate contraception for fertile participants. 14. Any contraindications to the use of Granulocyte colony-stimulating factor (G-CSF) or plerixafor during the mobilization of HSCs, and any contraindications to the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations. 15. Known hypersensitivity to protamine sulfate.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Lenti-D Drug Product 		Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of > or = 5.0*10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) following myeloablative conditioning with busulfan and fludarabine on Day 1.
  • Genetic: Lenti-D
    Participants received a single IV infusion of Lenti-D Drug Product.
    Other names:
    • elivaldogene autotemcel
    • eli-cel

More Details

Status
Completed
Sponsor
bluebird bio

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.