Metachromatic Leukodystrophy (MLD)NCT03725670
Direct Lentiviral Injection Gene Therapy for MLD
A study testing Intrathecal and intravenous LV gene therapy in people with Metachromatic Leukodystrophy (MLD), run by Shenzhen Geno-Immune Medical Institute at 1 site in China.
Trial summary
This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy improved self-inactivating lentiviral vector TYF-ARSA to functionally correct the genetic defect. Read more about this study
- Who is it for?
- Ages 1 month to 50 years
- Conditions the study is for
- Metachromatic Leukodystrophy (MLD)
- What is being tested?
- Intrathecal and intravenous LV gene therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 31 May 2027to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- MLD patient age >= 1 month
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Lung-Ji Chang
Shenzhen, Guangdong, 518000
Lung-Ji Chang, Ph.D, +86 0755-86573763, c@mkgimi.com
About this study
Official title: Direct Lentiviral TYF-ARSA Injection Gene Therapy for Metachromatic Leukodystrophy (MLD)
This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy 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 direct gene transfer clinical protocol.
Read the detailed description
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
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 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 efficacy improved self-inactivating lentiviral vector (LV) carrying a functional MLD gene to correct the genetic defect by intrathecal (IT) and intravenous (IV) injections to delivery the lentiviral vector carrying a normal ARSA gene to correct the genetic defect. The primary objectives are to evaluate the safety of the improved LV TYF-ARSA and the direct injection gene transfer clinical protocol, the efficacy of degradative metabolite in patients after treatment, vector integration profile, and finally the long-term correction of the related pathological symptoms.
- Conditions
- Metachromatic Leukodystrophy (MLD)
- Being tested
- Intrathecal and intravenous LV gene therapy
- Keywords
- Metachromatic leukodystrophy (MLD), lentiviral vector, Intrathecal injection, Intravenous injection
- Medical subject headings
- Leukodystrophy, Metachromatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal and intravenous LV gene therapyGenetic
Direct IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10^9 transduction units/ml which carry a normal ARSA gene
| Study group | Role | What they receive |
|---|---|---|
| Lentivirus-mediated delivery of ARSA to the CNS and the body | Experimental | Intrathecal and intravenous injections with lentiviral TYF-ARSA vector carrying the functional gene Receives: Genetic: Intrathecal and intravenous LV gene therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of IT and IV injections of lentiviral TYF-ARSA
Safety of IT and IV injections 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 the study drug(s). The grade of AEs will be summarized if related to the treatment.
Measured: up to 1 year follow up
Altered disease progression
Altered disease progression based on biochemical analysis.
Measured: up to 3 year follow up after treatment
Altered disease progression
Altered disease progression based on MRI brain imaging analysis
Measured: up to 3 year follow up after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2018
- Study start31 May 2027 (estimated)
- Primary completion1 Jun 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metachromatic Leukodystrophy (MLD)Studies of the same condition, open and under way.
- More trials run by Shenzhen Geno-Immune Medical InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen Geno-Immune Medical Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lung-Ji Chang, Ph.D, Principal investigator, Shenzhen Geno-Immune Medical Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03725670
- Sponsor's protocol ID
- GIMI-IRB-18005
- Status last verified
- Oct 2026
- First submitted
- 25 Sep 2018
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Lentiviral TYF-ARSA Injection Gene Therapy for Metachromatic Leukodystrophy (MLD)
- ClinicalTrials.gov ID
- NCT03725670
- Acronym / sponsor ID
- GIMI-IRB-18005
- Conditions
- Metachromatic Leukodystrophy (MLD)
- Keywords
- Metachromatic leukodystrophy (MLD), lentiviral vector, Intrathecal injection, Intravenous injection
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Shenzhen Geno-Immune Medical InstituteUniversity, hospital or other
- Study start
- 31 May 2027 (estimated)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 31 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy 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 direct gene transfer clinical protocol.
Detailed description
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
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 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 efficacy improved self-inactivating lentiviral vector (LV) carrying a functional MLD gene to correct the genetic defect by intrathecal (IT) and intravenous (IV) injections to delivery the lentiviral vector carrying a normal ARSA gene to correct the genetic defect. The primary objectives are to evaluate the safety of the improved LV TYF-ARSA and the direct injection gene transfer clinical protocol, the efficacy of degradative metabolite in patients after treatment, vector integration profile, and finally the long-term correction of the related pathological symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lentivirus-mediated delivery of ARSA to the CNS and the body | Experimental | Genetic: Intrathecal and intravenous LV gene therapyIntrathecal and intravenous injections with lentiviral TYF-ARSA vector carrying the functional gene |
Who may qualify
- Ages
- 1 month to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- MLD patient age >= 1 month
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal and intravenous LV gene therapyDirect IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10^9 transduction units/ml which carry a normal ARSA gene | Genetic | Lentivirus-mediated delivery of ARSA to the CNS and the body |
Primary outcome
Safety of IT and IV injections of lentiviral TYF-ARSA
Time frame: up to 1 year follow up
Safety of IT and IV injections 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 the study drug(s). The grade of AEs will be summarized if related to the treatment.
Altered disease progression
Time frame: up to 3 year follow up after treatment
Altered disease progression based on biochemical analysis.
Altered disease progression
Time frame: up to 3 year follow up after treatment
Altered disease progression based on MRI brain imaging analysis
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lung-Ji Chang, Ph.D principal investigator
Shenzhen Geno-Immune Medical Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intrathecal and intravenous LV gene therapy in people with Metachromatic Leukodystrophy (MLD), run by Shenzhen Geno-Immune Medical Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lung-Ji Chang, Ph.D (+86 0755-86573763, c@mkgimi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of IT and IV injections of lentiviral TYF-ARSA (time frame: up to 1 year follow up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.