A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Cerebral Adrenoleukodystrophy (CALD)
About this trial
This is an interventional treatment trial for Cerebral Adrenoleukodystrophy (CALD) focused on measuring Adrenoleukodystrophy, X-linked adrenoleukodystrophy, Gene therapy, Hematopoietic stem cell
Eligibility Criteria
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 participants, in accordance with the directive of the IRB/IEC and with local requirements.
- Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
Active cerebral ALD as defined by:
- Elevated very long chain fatty acids (VLCFA) values, 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 on MRI of demyelinating lesions.
- NFS < or = 1.
Exclusion Criteria:
- Prior receipt of an allogeneic transplant or gene therapy.
- 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.
- 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.
- Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
Hematological compromise as evidenced by:
- Peripheral blood absolute neutrophil count (ANC) count <1500 cells/ cubic millimeter (mm^3), and either
- Platelet count <100,000 cells/mm^3, or
- Hemoglobin <10 gram per deciliter (g/dL).
Hepatic compromise as evidenced by:
- Aspartate transaminase (AST) value greater than (>) 2.5 × upper limit of normal (ULN)
- Alanine transaminase (ALT) value >2.5 × ULN
- 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
- Baseline estimated glomerular filtration rate <70 milliliter per minute (mL/min)/1.73 square meter (m^2).
- Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%).
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection.
- Positive for HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1).
- Any clinically significant cardiovascular, hematological, or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
- Absence of adequate contraception for fertile participants.
- Any contraindications to the use of Granulocyte colony-stimulating factor (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.
- Known hypersensitivity to protamine sulfate.
Sites / Locations
- Lucile Packard Children's Hospital
- Boston Children's Hospital/Massachusetts General Hospital
- University of Minnesota
- Hôpital Robert Debré
- Universitätsklinikum Leipzig AöR
- Ospedale Pediatrico Bambino Gesù
- Prinses Maxima Center
- UCL-ICH/Great Ormond Street Hospital
Arms of the Study
Arm 1
Experimental
Lenti-D Drug Product
Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of > or = 5.0*10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) following myeloablative conditioning with busulfan and fludarabine on Day 1.