Lentiviral Gene Therapy for X-ALD

Status Recruiting

Clinical Trial 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.

Clinical Trial 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 Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT03727555
Study type	Interventional
Source	Shenzhen Geno-Immune Medical Institute
Contact	Lung-Ji Chang, Ph.D
Phone	86-0755-86725195
Email	c@szgimi.org
Status	Recruiting
Phase	N/A
Start date	October 30, 2018
Completion date	October 30, 2020

View Details

See also
Status	Clinical Trial	Phase
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Completed	`NCT02595489` - A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy	Phase 1
Completed	`NCT01594853` - Exercise Study of Function and Pathology for Women With X-linked Adrenoleukodystrophy	N/A
Completed	`NCT04687007` - SMART-ALD - A New Lifestyle Intervention to Improve Quality of Life in Women With X-linked Adrenoleukodystrophy (X-ALD)	N/A
Completed	`NCT01165060` - The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD)	N/A
Recruiting	`NCT05939232` - Registry of X-linked Adrenoleukodystrophy
Active, not recruiting	`NCT02699190` - LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
Completed	`NCT03864523` - Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy	Phase 2
Recruiting	`NCT06178120` - Disease Progression in Women With X-linked Adrenoleukodystrophy
Recruiting	`NCT03278899` - A Study to Prospectively Assess Disease Progression in Male Children With X-ALD
Recruiting	`NCT03047369` - The Myelin Disorders Biorepository Project
Recruiting	`NCT04675749` - Quality of Life in Women With X-linked Adrenoleukodystrophy
Withdrawn	`NCT03196765` - Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects With Adrenoleukodystrophy	Phase 1/Phase 2
Withdrawn	`NCT01787578` - Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)	Phase 1
No longer available	`NCT02233257` - Expanded Access for Lorenzo's Oil (GTO/GTE) in Adrenoleukodystrophy	N/A

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.