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Lentiviral Gene Therapy for MLD

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: NCT03725670
Recruitment Status : Unknown
Verified September 2019 by Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : October 31, 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 transfer for treating Metachromatic leukodystrophy (MLD) using a safety and efficiency improved self-inactivating lentiviral vector TYF-ARSA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.

Condition or disease Intervention/treatment Phase
Metachromatic Leukodystrophy (MLD) Biological: Lentivirus-mediated delivery of ARSA to the CNS. Not Applicable

Detailed Description:
Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease. This disease is an inherited single gene autosomal recessive defect. MLD is caused by a mutation in the ARSA gene encoding arylsulfatase A which leads to a deficiency in sulfatide degradation, resulting in its accumulation in oligodendrocytes, Schwann cells and some neurons. A critical level of sulfatide storage can trigger demyelination, the hallmark of MLD, which results in multiple neurological symptoms. MLD has different onset ages including late infancy (1-2 years), adolescence (4 years-before sexual maturity) and adulthood (after sexual maturity). MLD patients are normally rescued by hematopoietic stem cell transplantation (HSCT) from a matched healthy donor. However, HSCT must be performed at a very early stage of the disease thus restricting its therapeutic opportunies in MLD patients. This trial aims to treat MLD using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional MLD gene to correct the genetic defect by intracerebral injection to delivery the lentiviral vector carrying a normal ARSA gene to correct the pathogenic defect. The primary objectives are to evaluate the safety of the improved self-inactivating lentiviral vector TYF-ARSA, 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 the related pathological symptoms.

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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: Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA)
Actual Study Start Date : October 30, 2018
Actual Primary Completion Date : October 30, 2018
Estimated Study Completion Date : November 1, 2020

Arm Intervention/treatment
Experimental: Lentivirus-mediated delivery of ARSA to the CNS.
Intracerebral injection with lentiviral TYF-ARSA vector carrying the functional gene
Biological: Lentivirus-mediated delivery of ARSA to the CNS.
Intracerebral LV gene therapy to deliver high level lenviral vectors which carry normal ARSA gene at 1-2×10^9 multiplicity of infection (moi)/ml per site.

Primary Outcome Measures :
  1. Safety of intracerebral injection of lentiviral TYF-ARSA. [ Time Frame: up to 1 year follow up ]
    Safety of intracerebral injection of lentiviral TYF-ARSA, 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: up to 3 year follow up after treatment ]
    Altered disease progression based on biochemical analysis and MRI brain imaging analysis.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. MLD patient age >= 0 year
  2. ARSA gene sequence analysis to confirm MLD mutations
  3. Scoring system for brain MR Imaging confirmed MLD
  4. Parent / guardian / patient signing informed consent
  5. 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. Patients who are experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
  3. Cannot perform an MRI
  4. Infection or dermatosis at pre-injection site
  5. Any condition that may increase the subjects' risk or interfere with the results of the trial. In addition to MLD, there are other neurological disorders.

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): NCT03725670

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

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China, Guangdong
Lung-Ji Chang Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, Ph.D    86-0755-86725195   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
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Principal Investigator: Lung-Ji Chang, Ph.D Shenzhen Geno-Immune Medical Institute
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Responsible Party: Shenzhen Geno-Immune Medical Institute Identifier: NCT03725670    
Other Study ID Numbers: GIMI-IRB-18005
First Posted: October 31, 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:
Metachromatic leukodystrophy (MLD)
lentiviral vector
Additional relevant MeSH terms:
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Leukodystrophy, Metachromatic
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lysosomal Storage Diseases, Nervous System
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders