|
Key inclusion & exclusion criteria
|
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.
Age minimum:
N/A
Age maximum:
17 Years
Gender:
Male
|
|
Secondary Outcome(s)
|
|
Detectable vector copy number (VCN) in peripheral blood cells by Month 6
[Time Frame: Month 6 post-transplant]
|
|
Percentage of participants with adverse events (AEs) in selected categories
[Time Frame: Month 24 post-transplant]
|
|
Time to neutrophil engraftment post-drug product infusion
[Time Frame: 42 days post-drug product infusion]
|
|
Change in total neurologic function Score (NFS) from baseline to protocol scheduled visits
[Time Frame: From Baseline through study completion (up to Month 24 [+or- 1 month] post-transplant)]
|
|
Percentage of participants with loss of neutrophil engraftment post-drug product infusion by Month 24
[Time Frame: Month 24 post-drug product infusion]
|
|
Time to platelet engraftment post-drug product infusion
[Time Frame: up to Month 24 post-drug product infusion]
|
|
Number of participants in which vector-derived replication competent lentivirus (RCL) is detected by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Number of participants with insertional oncogenesis by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants who undergo a subsequent hematopoietic stem cell (HSC) infusion by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Duration of in-patient hospitalizations (post-neutrophil engraftment) by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Duration of intensive care units (ICU) stays (post-neutrophil engraftment) by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Major functional disability (MFD)-free survival over time
[Time Frame: up to Month 24 (+or- 1 month) post-transplant]
|
|
Number of in-patient hospitalizations (post-neutrophil engraftment) by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Number of intensive care units (ICU) stays (post-neutrophil engraftment) by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Number of emergency room visits (post-neutrophil engraftment) by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants who experience greater than or equal to (> or =) Grade II acute GVHD by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants who experience transplant-related mortality through 100 and 365 days post-drug product infusion
[Time Frame: Through 100 and 365 days post-drug product infusion]
|
|
Percentage of participants with platelet engraftment by Month 24
[Time Frame: Month 24 post-drug product infusion]
|
|
Overall survival
[Time Frame: up to Month 24 (+or- 1 month) post-transplant]
|
|
Percentage of participants who experience chronic GVHD by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants who experience either acute (greater than or equal to [> or =] Grade II) or chronic graft versus host disease (GVHD) at Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants with potentially clinically significant changes in laboratory parameters by Month 24
[Time Frame: Month 24 post-transplant]
|
|
Percentage of participants without gadolinium enhancement (GdE) at Month 24
[Time Frame: Month 24 post-transplant]
|