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Lentiviral Gene Therapy for X-ALD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03727555
Recruitment Status : Unknown
Verified September 2019 by Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : November 1, 2018
Last Update Posted : September 19, 2019
Information provided by (Responsible Party):
Shenzhen Geno-Immune Medical Institute

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.

Condition or disease Intervention/treatment Phase
X-linked Adrenoleukodystrophy Genetic: Intracerebral LV gene therapy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)
Actual Study Start Date : October 30, 2018
Actual Primary Completion Date : October 30, 2018
Estimated Study Completion Date : October 30, 2020

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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.

  2. Altered disease progression [ Time Frame: Minimum 6 months, maximum 3 year follow up ]
    Altered disease progression based on biochemical analysis.

  3. Assess disease progression [ Time Frame: Minimum 6 months, maximum 3 year follow up ]
    Assess disease progression based on MRI brain imaging analysis.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT03727555

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Contact: Lung-Ji Chang, Ph.D 86-0755-86725195

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China, Guangdong
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, PhD    86-0755-86725195   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
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Responsible Party: Shenzhen Geno-Immune Medical Institute Identifier: NCT03727555    
Other Study ID Numbers: GIMI-IRB-18006
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shenzhen Geno-Immune Medical Institute:
X-linked adrenoleukodystrophy
Lentiviral vector
Additional relevant MeSH terms:
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Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
Demyelinating Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Metabolism, Inborn Errors
Peroxisomal Disorders
Metabolic Diseases
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases