Brief Title
Lentiviral Gene Therapy for X-ALD
Official Title
Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)
Brief Summary
This is a Phase I/II clinical trial of gene therapy for treating X-linked adrenoleukodystrophy using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF-ABCD1 to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.
Detailed Description
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1). ABCD1 is responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. X-ALD is clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the inflammatory cerebral ALD. This diease presents most commonly in males. Approximately 50% of heterozygote females show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. The disease is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. ALD patients are normally treated with haematopoietic stem cell transplantation (HSCT) from a matched healthy donor. However, HSCT must be performed at a very early stage of the disease, which limits the therapeutic opportunies for juvenile or adult forms of ALD. This trial aims to treat ALD using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ABCD1 gene to correct the genetic defect. By Intracerebral injection to delivery the lentiviral vector with a normal ALD gene to correct the pathologies associated with this genetic defect. The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-ABCD1, the in-vivo gene transfer clinical protocol and the efficacy of degradative metabolite in patients at the time of treatment, assessment of vector integration sites, and finally the long-term correction of patients' disease beheviors.
Study Type
Interventional
Primary Outcome
Safety evaluation of intracerebral injection of lentiviral TYF-ABCD1, determined by number of participants with treatment-related adverse events (AEs), according to scheduled assessments, vital signs, & physical examinations as assessed by CTCAE v4.0.
Condition
X-linked Adrenoleukodystrophy
Intervention
Intracerebral LV gene therapy
Study Arms / Comparison Groups
Lentivirus-mediated delivery of ABCD1 to the CNS.
Description: Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
10
Start Date
October 30, 2018
Completion Date
October 30, 2020
Primary Completion Date
October 30, 2018
Eligibility Criteria
Inclusion Criteria: 1. X-ALD patients ≥0 years of age 2. ALD diagnosis of the brain: evaluation of the VLCFA value in plasma 3. Central imaging of the MRI to examine the damage on the CNS. 4. Neurological function score (NFS) ≥ 1 5. Parent / guardian / patient signing informed consent 6. Patients and their families have a strong willingness to participate in clinical trials, and are willing to bear all the consequences caused by the failure of the trial, and sign an informed consent form Exclusion Criteria: 1. HIV positive patients 2. Stablized condition after statins, Lorenzoas oil, or diet to reduce VLCFA levels 3. Patients who are experiencing severe viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency 4. Cannot perform an MRI 5. Infection or dermatosis at pre-injection site
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
, 86-0755-86725195, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT03727555
Organization ID
GIMI-IRB-18006
Responsible Party
Sponsor
Study Sponsor
Shenzhen Geno-Immune Medical Institute
Study Sponsor
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Verification Date
September 2019