Lentiviral Gene Therapy for X-ALD

checkorphan
Learn more about:
X-linked adrenoleukodystrophy
Related Access Program
University of Minnesota – Clinical and Translational Science Institute – X-linked Adrenoleukodystrophy
Related Clinical Trial
Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy and Metachromatic Leukodystrophy SMART-ALD – A New Lifestyle Intervention to Improve Quality of Life in Women With X-linked Adrenoleukodystrophy (X-ALD) Quality of Life in Women With X-linked Adrenoleukodystrophy A Clinical Study in Male Pediatric Patients With Cerebral X-linked Adrenoleukodystrophy (Cald) to Assess the Effects of MIN-102 Treatment on Disease Progression Prior to Human Stem Cell Transplant (HSCT) Plasma Exchange With Albumin in AMN Patients Stem Cell Transplant for Inborn Errors of Metabolism Human Placental-Derived Stem Cell Transplantation Precision Exercise in Children With Malignant Hemopathies Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects With Adrenoleukodystrophy Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy MD1003-AMN MD1003 in Adrenomyeloneuropathy A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients. Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD) A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants Autologous Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy and Adrenoleukodystrophy Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Clinical Study and Gene Mutation Analysis of Adrenoleukodystrophy in Taiwanese Children Early Diagnosis Of Childhood Cerebral ALD Randomized Study of Beta Interferon and Thalidomide in Patients With Adrenoleukodystrophy Multi-center Clinical Study on the Diagnosis and Treatment Management of Rare Neurological Disease in Children HSCT for High Risk Inherited Inborn Errors Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD) UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation (HaploHCT) Following Reduced Intensity Conditioning (RIC) for Selected High Risk Non-Malignant Diseases The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD) A Phase III Trial of Lorenzo’s Oil in Adrenomyeloneuropathy Lentiviral Gene Therapy for X-ALD MT2014-14 IT-MSC for Advanced Cerebral Adrenoleukodystrophy (cALD) Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD) Newborn Screening for Adrenoleukodystrophy A Study to Prospectively Assess Disease Progression in Male Children With X-ALD Long-term Follow-up of Subjects With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product Exercise Study of Function and Pathology for Women With X-linked Adrenoleukodystrophy Expanded Access for Lorenzo’s Oil (GTO/GTE) in Adrenoleukodystrophy Minnesota Adrenoleukodystrophy Registry Study (MARS) and Biobank A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy Effect of Glycerol Trierucate on Clinical Course of Adrenoleukodystrophy

Brief Title

Lentiviral Gene Therapy for X-ALD

Official Title

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

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.

Study Type

Interventional

Primary Outcome

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.

Condition

X-linked Adrenoleukodystrophy

Intervention

Intracerebral LV gene therapy

Study Arms / Comparison Groups

 Lentivirus-mediated delivery of ABCD1 to the CNS.
Description:  Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Genetic

Estimated Enrollment

10

Start Date

October 30, 2018

Completion Date

October 30, 2020

Primary Completion Date

October 30, 2018

Eligibility Criteria

        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

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, 86-0755-86725195, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations

NCT ID

NCT03727555

Organization ID

GIMI-IRB-18006

Responsible Party

Sponsor

Study Sponsor

Shenzhen Geno-Immune Medical Institute

Study Sponsor

, ,

Verification Date

September 2019