Lentiviral Gene Therapy for X-ALD
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|ClinicalTrials.gov Identifier: NCT03727555|
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : November 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|X-linked Adrenoleukodystrophy||Genetic: Intracerebral LV gene therapy||Not Applicable|
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 (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||October 30, 2018|
|Estimated Study Completion Date :||October 30, 2020|
Experimental: Lentivirus-mediated delivery of ABCD1 to the CNS.
Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene
Genetic: Intracerebral LV gene therapy
Intracerebral LV gene therapy to deliver high levels lenvirus which carry normal ABCD1 gene at 1-2×10^9 multiplicity of infection/ml per site in multiple sites.
- 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. [ Time Frame: Minimum 1 day, maximum 1 year follow up ]Safety 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. AEs & clinically significant abnormalities (meeting grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity & relationship to study drug(s). Grade 1 & 2 AEs will be summarized if related to study therapy.
- Altered disease progression [ Time Frame: Minimum 6 months, maximum 3 year follow up ]Altered disease progression based on biochemical analysis.
- Assess disease progression [ Time Frame: Minimum 6 months, maximum 3 year follow up ]Assess disease progression based on MRI brain imaging analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727555
|Contact: Lung-Ji Chang, Ph.Dfirstname.lastname@example.org|
|Shenzhen Geno-immune Medical Institute||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Lung-Ji Chang, PhD 86-0755-86725195 email@example.com|