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: 35
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

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.
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
8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%
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 HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1).
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.
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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