Current Environment:


Study ALD-104 is an international, non-randomized, open-label, multi-site study in male participants (Less than or equal to [< or =] 17 years of age at enrollment) with cerebral adrenoleukodystrophy (CALD). Approximately 35 participants will be infused with Lenti-D Drug Product after myeloablative conditioning with busulfan and fludarabine. This trial will evaluate the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of 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.


Cerebral Adrenoleukodystrophy (CALD)

Recruitment Status

Active, not recruiting

Eligibility Criteria

Inclusion Criteria:

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.
Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.

Active cerebral ALD as defined by:

Elevated very long chain fatty acids (VLCFA) values, and
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. Gadolinium enhancement on MRI of demyelinating lesions.

NFS < or = 1.

Exclusion Criteria:

Prior receipt of an allogeneic transplant or gene therapy.
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.
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.
Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).

Hematological compromise as evidenced by:

Peripheral blood absolute neutrophil count (ANC) count <1500 cells/ cubic millimeter (mm^3), and either
Platelet count <100,000 cells/mm^3, or
Hemoglobin <10 gram per deciliter (g/dL).

Hepatic compromise as evidenced by:

Aspartate transaminase (AST) value greater than (>) 2.5 × upper limit of normal (ULN)
Alanine transaminase (ALT) value >2.5 × ULN
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
Baseline estimated glomerular filtration rate <70 milliliter per minute (mL/min)/1.73 square meter (m^2).
Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%).
Immediate family member with a known or suspected Familial Cancer Syndrome.
Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection.
Positive for HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1).
Any clinically significant cardiovascular, hematological, or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
Absence of adequate contraception for fertile participants.
Any contraindications to the use of Granulocyte colony-stimulating factor (G-CSF) or plerixafor during the mobilization of hematopoietic stem cells, 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.
Known hypersensitivity to protamine sulfate.


Intervention Type

Intervention Name




Phase 3



Min Age


Max Age

17 Years

Download Date

April 4, 2022

Principal Investigator


Primary Contact Information

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