Lentiviral Gene Therapy for X-ALD
Primary Purpose
X-linked Adrenoleukodystrophy
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Intracerebral LV gene therapy
Sponsored by
About this trial
This is an interventional treatment trial for X-linked Adrenoleukodystrophy focused on measuring X-linked adrenoleukodystrophy, Lentiviral vector
Eligibility Criteria
Inclusion Criteria:
- X-ALD patients ≥0 years of age
- ALD diagnosis of the brain: evaluation of the VLCFA value in plasma
- Central imaging of the MRI to examine the damage on the CNS.
- Neurological function score (NFS) ≥ 1
- 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
- Stablized condition after statins, Lorenzoas oil, or diet to reduce VLCFA levels
- Patients who are experiencing severe 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
Sites / Locations
- Shenzhen Geno-immune Medical InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lentivirus-mediated delivery of ABCD1 to the CNS.
Arm Description
Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene
Outcomes
Primary Outcome Measures
Safety evaluation of intracerebral injection of lentiviral TYF-ABCD1, 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.
Safety of intracerebral injection of lentiviral TYF-ABCD1, 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
Altered disease progression based on biochemical analysis.
Assess disease progression
Assess disease progression based on MRI brain imaging analysis.
Secondary Outcome Measures
Full Information
NCT ID
NCT03727555
First Posted
September 25, 2018
Last Updated
September 18, 2019
Sponsor
Shenzhen Geno-Immune Medical Institute
1. Study Identification
Unique Protocol Identification Number
NCT03727555
Brief Title
Lentiviral Gene Therapy for X-ALD
Official Title
Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 30, 2018 (Actual)
Primary Completion Date
October 30, 2018 (Actual)
Study Completion Date
October 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shenzhen Geno-Immune Medical Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase I/II clinical trial of gene therapy for treating X-linked adrenoleukodystrophy using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF-ABCD1 to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.
Detailed Description
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1). ABCD1 is responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. X-ALD is clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the inflammatory cerebral ALD. This diease presents most commonly in males. Approximately 50% of heterozygote females show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. The disease is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. ALD patients are normally treated with haematopoietic stem cell transplantation (HSCT) from a matched healthy donor. However, HSCT must be performed at a very early stage of the disease, which limits the therapeutic opportunies for juvenile or adult forms of ALD. This trial aims to treat ALD using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ABCD1 gene to correct the genetic defect. By Intracerebral injection to delivery the lentiviral vector with a normal ALD gene to correct the pathologies associated with this genetic defect.
The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-ABCD1, 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 patients' disease beheviors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
X-linked Adrenoleukodystrophy
Keywords
X-linked adrenoleukodystrophy, Lentiviral vector
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lentivirus-mediated delivery of ABCD1 to the CNS.
Arm Type
Experimental
Arm Description
Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene
Intervention Type
Genetic
Intervention Name(s)
Intracerebral LV gene therapy
Intervention Description
Intracerebral LV gene therapy to deliver high levels lenvirus which carry normal ABCD1 gene at 1-2×10^9 multiplicity of infection/ml per site in multiple sites.
Primary Outcome Measure Information:
Title
Safety evaluation of intracerebral injection of lentiviral TYF-ABCD1, 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.
Description
Safety of intracerebral injection of lentiviral TYF-ABCD1, 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.
Time Frame
Minimum 1 day, maximum 1 year follow up
Title
Altered disease progression
Description
Altered disease progression based on biochemical analysis.
Time Frame
Minimum 6 months, maximum 3 year follow up
Title
Assess disease progression
Description
Assess disease progression based on MRI brain imaging analysis.
Time Frame
Minimum 6 months, maximum 3 year follow up
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
X-ALD patients ≥0 years of age
ALD diagnosis of the brain: evaluation of the VLCFA value in plasma
Central imaging of the MRI to examine the damage on the CNS.
Neurological function score (NFS) ≥ 1
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
Stablized condition after statins, Lorenzoas oil, or diet to reduce VLCFA levels
Patients who are experiencing severe 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lung-Ji Chang, Ph.D
Phone
86-0755-86725195
Email
c@szgimi.org
Facility Information:
Facility Name
Shenzhen Geno-immune Medical Institute
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lung-Ji Chang, PhD
Phone
86-0755-86725195
Email
c@szgimi.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Lentiviral Gene Therapy for X-ALD
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