- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03725670
Lentiviral Gene Therapy for MLD
September 18, 2019 updated by: Shenzhen Geno-Immune Medical Institute
Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA)
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
10
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Lung-Ji Chang, Ph.D
- Phone Number: 86-0755-86725195
- Email: c@szgimi.org
Study Locations
-
-
Guangdong
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Shenzhen, Guangdong, China, 518000
- Recruiting
- Lung-Ji Chang
-
Contact:
- Lung-Ji Chang, Ph.D
- Phone Number: 86-0755-86725195
- Email: c@szgimi.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- MLD patient age >= 0 year
- ARSA gene sequence analysis to confirm MLD mutations
- Scoring system for brain MR Imaging confirmed MLD
- Parent / guardian / patient signing informed consent
- 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:
- HIV positive patients
- Patients who are experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
- Cannot perform an MRI
- Infection or dermatosis at pre-injection site
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lentivirus-mediated delivery of ARSA to the CNS.
Intracerebral injection with lentiviral TYF-ARSA vector carrying the functional gene
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
up to 1 year follow up
|
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.
|
up to 3 year follow up after treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 30, 2018
Primary Completion (Actual)
October 30, 2018
Study Completion (Anticipated)
November 1, 2020
Study Registration Dates
First Submitted
September 25, 2018
First Submitted That Met QC Criteria
October 29, 2018
First Posted (Actual)
October 31, 2018
Study Record Updates
Last Update Posted (Actual)
September 19, 2019
Last Update Submitted That Met QC Criteria
September 18, 2019
Last Verified
September 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Demyelinating Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Leukoencephalopathies
- Hereditary Central Nervous System Demyelinating Diseases
- Sulfatidosis
- Leukodystrophy, Metachromatic
Other Study ID Numbers
- GIMI-IRB-18005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metachromatic Leukodystrophy (MLD)
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ShireCompletedMetachromatic Leukodystrophy (MLD)Australia, Denmark, Japan, France, Germany
-
ShireTakeda Development Center Americas, Inc.Active, not recruitingMetachromatic Leukodystrophy (MLD)Denmark, Germany, Japan, Australia, France, Brazil, Czechia
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TakedaWithdrawnMetachromatic Leukodystrophy (MLD)Spain
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ShireTakeda Development Center Americas, Inc.Active, not recruitingMetachromatic Leukodystrophy (MLD)United States, Canada, Belgium, Israel, Netherlands, United Kingdom, Germany, Spain, Japan, Brazil, Argentina, France, Greece, Italy
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ShireCompletedMetachromatic Leukodystrophy (MLD)Denmark
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ShireCompletedLate Infantile Metachromatic LeukodystrophyDenmark
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