Lentiviral Gene Therapy for X-ALD

X-linked Adrenoleukodystrophy Clinical Trial

Official title:

Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03727555
• Other study ID #: GIMI-IRB-18006
• Status: Recruiting
• Phase: N/A
• Start date: October 30, 2018
• Est. completion date: October 30, 2020

Study information

• Verified date: September 2019
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, Ph.D
• Phone: 86-0755-86725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. X-ALD patients =0 years 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, Lorenzoas 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

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• X-linked Adrenoleukodystrophy

Intervention

Genetic:
• Intracerebral LV gene therapy
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.

Locations

Country	Name	City	State
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Minimum 1 day, maximum 1 year follow up
Primary	Altered disease progression	Altered disease progression based on biochemical analysis.	Minimum 6 months, maximum 3 year follow up
Primary	Assess disease progression	Assess disease progression based on MRI brain imaging analysis.	Minimum 6 months, maximum 3 year follow up