A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Childhood Cerebral Adrenoleukodystrophy (CCALD)

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 subjects, in accordance with the directive of the IRB/IEC and with local requirements).
• Boys aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.

• Active cerebral ALD as defined by: Elevated VLCFA levels, 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 of demyelinating lesions on MRI.

• NFS ≤ 1.

Exclusion Criteria:

• Receipt of an allogeneic transplant or gene therapy.
• Availability of a willing 10/10 human leukocyte antigen (HLA)-matched sibling donor.
• Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: subjects must discontinue use of these medications at time of consent.
• Receipt of an investigational study drug or procedure within 3 months before Day -60 that might confound study outcomes.
• Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).

• Hematological compromise as evidenced by:

  i. Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm^3 or, ii. Platelet count < 100,000 cells/mm^3 or, iii. Hemoglobin < 10 g/dL or, iv. Uncorrected bleeding disorder.

• Hepatic compromise as evidenced by:

  i. Aspartate transaminase (AST) value > 2.5 × the upper limit of normal (ULN) or, ii. Alanine transaminase (ALT) value > 2.5 × ULN or, iii. Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable.

• Renal compromise as evidenced by abnormal renal function (creatinine clearance < 50 mL/min).
• Cardiac compromise as evidenced by left ventricular ejection fraction < 40%.
• Immediate family member with a known or suspected Familial Cancer Syndrome.
• Clinically significant active bacterial, viral, fungal, or parasitic infection.
• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1, HIV 2), hepatitis B, hepatitis C, or human T lymphotrophic virus 1 (HTLV 1).
• Any clinically significant cardiovascular or pulmonary, or other disease or condition that would be contraindicated for any of the other study procedures.