Clinical Trial: Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I Study of Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy

Brief Summary:

Background:

- The Gigaxonin gene lets the body make a protein chemical called Gigaxonin. Nerves need Gigaxonin to work properly. Giant Axonal Neuropathy (GAN) causes a shortage of functional Gigaxonin. Nerves stop working normally in people with GAN. This causes problems with walking and sometimes with eating, breathing, and many other activities. GAN has no cure. Over time, GAN can shorten a person s life. Researchers want to see if a gene transfer treatment may help people with GAN.

Objectives:

- To see if a gene transfer is safe and shows potential to help people with GAN.

Eligibility:

- People age 5 and older with GAN.

Design:

  • For 2 months participants must live full-time within 100 miles of the NIH.
  • Participants will be screened by phone and in person. They will take many tests. Some are listed below. Their medical records will be reviewed. Their caregivers may be contacted.
  • Participants will have a total of about 30 visits, weekly, monthly, and then yearly over 15 years. They will include many of the tests below.
  • Physical and nervous system exams.
  • Blood, urine, and stool samples.
  • Nerve, lung, heart, and eye tests.
  • Questionnaires.
  • MRI scans, nerve biopsies, and spinal taps. Participants will be sedated for some tests.
  • Speech, memory, muscle, and mobility tests.

    • Detailed Summary:

    This is a non-randomized, phase I, escalating single dose study to assess the safety of the gene transfer vector scAAV9/JeT-GAN through intrathecal delivery to the brain and spinal cord of patients with Giant Axonal Neuropathy (GAN, OMIM No.256850). The primary objective of this study is to assess the safety of the vector following intrathecal delivery in 6-8 GAN patients with at least one missense change, five years of age or older; as well as a single GAN patient, 5 years or older who does not have any missense changes in the GAN gene ('null mutation patient'). Secondary objectives of this study are 1) to assess motor and sensory disease symptoms pre- and post-treatment, 2) to examine neuropathology in peripheral nerve biopsies in response to treatment, 3) to examine cerebrospinal fluid (CSF) and to conduct CSF studies to assess response to treatment, and 4) to assess vector shedding following vector administration. The first eligible missense patient will have a genetic diagnosis of giant axonal neuropathy, will be seven years of age or older, and will have a forced vital capacity of greater than or equal to 50 percent predicted value on pulmonary function testing. This study will be the first-in-human trial of intrathecal delivery of scAAV9/JeT-GAN. The primary endpoint will be safety, based upon adverse events and standard laboratory safety evaluations. Secondary endpoints will include clinical and physiological assessment of motor and sensory function, possible rescue of disease pathology in peripheral nerves, examination of CSF in response to treatment, and assessment of vector shedding following administration.

    GAN is a chronic neurodegenerative autosomal recessive disease pathologically characterized by enlarged axons with disordered microtubules and intermediate filaments. The disease pathology is due to loss-of-function mutations in the GAN gene, which encodes
    Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

    Current Primary Outcome: To determine the relative safety of intrathecal administration of scAAV9/JeT-GAN in the treatment of Giant Axonal Neuropathy [ Time Frame: 8 weeks ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome: To determine the efficacy of scAAV9-JeT-GAN, measured by improvement of pathologic, histologic, physiologic, function, and clinical markers of Giant Axonal Neuropathy [ Time Frame: 3,6,9, 12 mo + yearly ]

    Original Secondary Outcome: Same as current

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: February 12, 2015
    Date Started: January 25, 2015
    Date Completion: April 1, 2030
    Last Updated: May 12, 2017
    Last Verified: March 28, 2017