Lentiviral Gene Therapy for MLD

• ClinicalTrials.gov Identifier: NCT03725670
• Recruitment Status: Unknown
• First Posted: October 31, 2018
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: September 25, 2018
• First Posted Date: October 31, 2018
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: October 30, 2018
• Actual Primary Completion Date: October 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2018)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lentiviral Gene Therapy for MLD
• Official Title: Gene Therapy for Metachromatic Leukodystrophy (MLD) Using a Self-inactivating Lentiviral Vector (TYF-ARSA)
• 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.
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metachromatic Leukodystrophy (MLD)

Intervention

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.

Study Arms

Experimental: Lentivirus-mediated delivery of ARSA to the CNS.

Intracerebral injection with lentiviral TYF-ARSA vector carrying the functional gene

Intervention: Biological: Lentivirus-mediated delivery of ARSA to the CNS.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 29, 2018): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 1, 2020
• Actual Primary Completion Date: October 30, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03725670
• Other Study ID Numbers: GIMI-IRB-18005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang, Ph.D; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019