Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

• Status: Recruiting
• Trial end date: 2023-02-16
• Target enrollment: 20
• Participant gender: Male

Summary

Study ALD-104 is an international, non-randomized, open-label, multi-site study in male subjects with CALD (≤17 years of age at enrollment). Approximately 20 subjects 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 CD34+ hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of cerebral adrenoleukodystrophy (CALD). A subject'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 subject following myeloablative conditioning.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: bluebird bio
• Treatments: Fludarabine

Criteria

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:

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. Gadolinium enhancement on MRI of demyelinating lesions.

4. Neurologic Function Score (NFS) ≤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:

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:

1. Peripheral blood ANC count <1500 cells/mm3,

2. Platelet count <100,000 cells/mm3, or

3. Hemoglobin <10 g/dL.

4. Uncorrected bleeding disorder.

6. Hepatic compromise as evidenced by:

1. Aspartate transaminase (AST) value >2.5 × ULN

2. Alanine transaminase (ALT) value >2.5 × ULN

3. 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 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.