NCT07046338

Brief 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 transduce patient-derived hematopoietic stem cells (HSCs), with the goal of achieving therapeutic gene correction through transplantation of genetically modified HSCs. The primary objectives are to evaluate the safety and efficacy of the gene therapy clinical protocol.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable

Timeline
54mo left

Started Jun 2025

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress17%
Jun 2025Sep 2030

Study Start

First participant enrolled

June 1, 2025

Completed
Same day until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2025

Completed
22 days until next milestone

First Submitted

Initial submission to the registry

June 23, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 1, 2025

Completed
5.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2030

Expected
Last Updated

July 1, 2025

Status Verified

June 1, 2025

Enrollment Period

Same day

First QC Date

June 23, 2025

Last Update Submit

June 23, 2025

Conditions

Metachromatic Leukodystrophy (MLD)

Keywords

Metachromatic leukodystrophy (MLD)Lentiviral vectorHematopoietic stem cells

Outcome Measures

Primary Outcomes (3)

  • Safety of auto-HSCs transduced with lentiviral TYF-ARSA

    Safety of HSCs transduced with 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. AEs will be graded if related to the treatment.

    up to 1 year follow up

  • Altered disease progression

    Altered disease progression based on biochemical analysis.

    up to 3 year follow up after treatment]

  • Altered disease progression

    Altered disease progression based on MRI brain imaging analysis.

    up to 3 year follow up after treatment]

Study Arms (1)

Lentiviral TYF-ARSA modified autologous HSCs

EXPERIMENTAL

Autologous HSCs transduced with lentiviral TYF-ARSA vector carrying the functional gene.

Genetic: Lentiviral TYF-ARSA correction of patient's autologous HSCs

Interventions

Lentiviral TYF-ARSA correction of patient's autologous HSCsGENETIC

Infusion of lentiviral TYF-ARSA modified autologous HSCs at 1\~10x10\^6 gene-modified cells per kg body weight.

Lentiviral TYF-ARSA modified autologous HSCs

Eligibility Criteria

Age1 Month - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • age \>= 1 month
  • ARSA gene sequence analysis to confirm MLD mutations
  • Brain MR Imaging
  • Parent / guardian / patient signing informed consent
  • Patients and their families have a strong willingness to participate in clinical trials, are willing to bear all the consequences caused by the failure of the trial, and sign the informed consent

You may not qualify if:

  • HIV positive
  • Experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
  • Cannot perform an MRI
  • Infection or dermatosis at infusion site
  • Any condition that may increase the subject's risk or interfere with the results of the trial, e.g. in addition to MLD, there are other neurological disorders.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Shenzhen Geno-Immune Medical Institute

Shenzhen, Guangdong, 518000, China

RECRUITING

MeSH Terms

Conditions

Leukodystrophy, Metachromatic

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesSulfatidosisSphingolipidosesLysosomal Storage Diseases, Nervous SystemLeukoencephalopathiesDemyelinating DiseasesMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLipidosesLipid Metabolism, Inborn ErrorsLysosomal Storage DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesLipid Metabolism Disorders

Central Study Contacts

Lung-Ji Chang, Ph.D

CONTACT

86-13671121909c@szgimi.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2025

First Posted

July 1, 2025

Study Start

June 1, 2025

Primary Completion

June 1, 2025

Study Completion (Estimated)

September 30, 2030

Last Updated

July 1, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)