IT and IV Lentiviral Gene Therapy for X-ALD

Intrathecal and Intravenous Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)

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 (LV) TYF-ABCD1 to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the intrathecal and intravenous lentiviral gene transfer clinical protocol.

Study Overview

• Status: Recruiting
• Conditions: X-linked Adrenoleukodystrophy
• Intervention / Treatment: Genetic: Intrathecal and intravenous LV gene therapy

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 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: Interventional
• Enrollment (Estimated): 30
• 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

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
      • 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: No

Description

Inclusion Criteria:

1. X-ALD patients ≥ 1 year of age
2. ALD diagnosis of the brain: evaluation of the VLCFA value in plasma
3. Central imaging of the MRI to examine the damage on the CNS.
4. Neurological function score (NFS) ≥ 1
5. Parent / guardian / patient signing informed consent
6. 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. Stablized condition after statins, Lorenzo's oil, or diet to reduce VLCFA levels
3. Patients who are experiencing severe viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
4. Cannot perform an MRI
5. 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)

Number of Arms

1

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	Genetic: Intrathecal and intravenous LV gene therapy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess disease progression	Assess disease progression based on MRI brain imaging analysis.	Minimum 6 months, maximum 3 year follow up
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.	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
Altered disease progression	Altered disease progression based on biochemicaland neurological analysis.	Minimum 6 months, maximum 3 year follow up

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: X-linked adrenoleukodystrophy; Lentiviral vector; Intrathecal injection; Intravenous injection
• 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)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No