IT and IV Lentiviral Gene Therapy for X-ALD
Intrathecal and Intravenous Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)
Study Overview
Status
Conditions
Intervention / Treatment
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.
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 with two main phenotypes: adrenomyeloneuropathy (AMN) and the inflammatory cerebral ALD. This disease 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 hematopoietic 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 opportunities 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 via intrathecal (IT) and intravenous (IV) injections to directly correct the genetic defect. This protocol targets not only early stage patients but also patients with symptoms. The direct LV injection approach aims to correct the pathologies associated with this genetic defect, and the IT and IV LV injections substantially simplify the treatment process, which reduces the risk associated with myeloablative chemotherapy during the HSCT treatment.
The objectives are to evaluate the safety of the advanced self-inactivating LV TYF-ABCD1, the direct in vivo gene transfer clinical protocol and the efficacy of the treatment, including assessment of vector distribution and the potential long-term correction of the ALD disease phenotype.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lung-Ji Chang, Ph.D
- Phone Number: 86-13671121909
- Email: c@szgimi.org
Study Contact Backup
- Name: Rui Zhang, MSc
- Phone Number: 86-13488887093
- Email: 13488887093@163.com
Study Locations
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Guangdong
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Shenzhen, Guangdong, China, 518000
- Shenzhen Geno-immune Medical Institute
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Contact:
- Lung-Ji Chang, PhD
- Phone Number: 86-13671121909
- Email: c@szgimi.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- X-ALD patients ≥ 1 year 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, Lorenzo's 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
Study Plan
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 ABCD1 to the CNS and the body
Intrathecal and intravenous injections with lentiviral TYF-ABCD1 vector carrying the functional gene
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Direct IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10^9 multiplicity of infection/ml which carry normal ABCD1 gene
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Assess disease progression
Time Frame: Minimum 6 months, maximum 3 year follow up
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Assess disease progression based on MRI brain imaging analysis.
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Minimum 6 months, maximum 3 year follow up
|
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Safety evaluation of IT and IV injections 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.
Time Frame: Minimum 1 day, maximum 1 year follow up
|
Safety of direct IT and IV injections 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.
|
Minimum 1 day, maximum 1 year follow up
|
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Altered disease progression
Time Frame: Minimum 6 months, maximum 3 year follow up
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Altered disease progression based on biochemicaland neurological analysis.
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Minimum 6 months, maximum 3 year follow up
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neurologic Manifestations
- Endocrine System Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Metabolism, Inborn Errors
- Genetic Diseases, Inborn
- Metabolic Diseases
- Neurobehavioral Manifestations
- Demyelinating Diseases
- Heredodegenerative Disorders, Nervous System
- Adrenal Gland Diseases
- Intellectual Disability
- Genetic Diseases, X-Linked
- Brain Diseases, Metabolic, Inborn
- Brain Diseases, Metabolic
- Hereditary Central Nervous System Demyelinating Diseases
- Leukoencephalopathies
- Adrenal Insufficiency
- Peroxisomal Disorders
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Nutritional and Metabolic Diseases
- X-Linked Intellectual Disability
- Adrenoleukodystrophy
Other Study ID Numbers
- GIMI-IRB-18006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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