Clinical study to assess the efficacy and safety of gene therapy for the treatment of cerebral adrenoleukodystrophy (CALD)

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: 35

Inclusion Criteria

1. Informed consent is obtained from a competent custodial parent or guardian
with legal capacity to execute a local IRB/IEC approved consent. Informed
assent will be sought from capable subjects, 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, subject assent.
3. Active cerebral ALD as defined by:
a. Elevated VLCFA values, and
b. 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.
4. Neurologic Function Score (NFS) = 1
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

2. 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.
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:
a. Peripheral blood ANC count < 1500 cells/mm3, and either
b. Platelet count < 100,000 cells/mm3 or
c. Hemoglobin < 10 g/dL.
6. Hepatic compromise as evidenced by:
a. Aspartate transaminase (AST) value >2.5 × ULN
b. Alanine transaminase (ALT) value >2.5 × ULN
c. Total bilirubin value >3.0 mg/dL, except if there is a diagnosis of
Gilbert’s Syndrome and the subject is otherwise stable
7. Baseline estimated glomerular filtration rate <70 mL/min/1.73 m2, as determined
using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation
(see https://www.kidney.org/professionals/KDOQI/gfr_calculatorPed)
8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%
9. Immediate family member with a known or suspected Familial Cancer Syndrome
(including but not limited to hereditary breast and ovarian cancer syndrome,
hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous
polyposis).
10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or
prionassociated
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 subjects 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. Subjects with past exposure to
HBV [HBcAb positive and/or HBeAb positive] are also eligible for the study
provided they have a negative test for HBV DNA. Also note that subjects 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 subjects. Male subjects and their
female partners are required to use two different effective methods of contraception
from Screening through at least 6 months after Lenti-D Drug Product infusion. If
subjects are truly sexually abstinent (where true sexual abstinence is defined as
being in line with the preferred and usual lifestyle of the subject), no second method
is required.
14. Any contraindications to the use of 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.
15. Known hypersensitivity to protamine sulfate.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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