Clinical Trial: Batten CLN6 Gene Therapy

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

Official Title: Phase I/IIa Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9

Brief Summary: The proposed clinical trial is the first human, open-label, single dose study of self-complementary AAV9 carrying the CLN6 gene delivered one-time intrathecally inserted by a lumbar puncture into Batten CLN6 Disease subjects. One cohort of patients with Batten CLN6 Disease, with confirmed diagnosis, will undergo gene transfer. A minimum of six patients will be enrolled into the cohort.

Detailed Summary: The proposed clinical trial is the first human, open-label, single dose study of self-complementary AAV9 carrying the CLN6 gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter (scAAV9.CB.CLN6) delivered one-time through an intrathecal catheter inserted by a lumbar puncture into the interspinous into the subarachnoid space of the lumbar thecal sac. All six patients will receive a dose equivalent to (1.5 x10^13 vg/kg). This will be administered premixed with 2.5 mL of the contrast Omnipaque™ at a concentration of 180 mgI/mL of the contrast via a 10 mL syringe and a Spinal Needle. If no clinically significant improvement without toxicity is observed, the possibility of adding an additional escalation cohort at a higher dose will be discussed with the FDA, DSMB and relevant oversight regulatory agencies.
Sponsor: Nationwide Children's Hospital

Current Primary Outcome: Development of unacceptable toxicity, defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity. [ Time Frame: 2 years ]

This is evaluated based on the development of unacceptable toxicity, defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Magnetic resonance imaging to document progression of the disease. [ Time Frame: Baseline and 24 months ]
    Volumetric imaging to monitor progression of the disease. The investigators will utilize 3D MP-RAGE scan, which is a T1-weighted volumetric scan of the whole brain. Investigators will also include T2 weighted Gradient Echo and diffusion- weighted axial images.
  • Cognitive testing [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    A retrospective review of cases indicates that language delay and cognitive regression are the earliest manifestations of the disease. The investigators will perform Stanford-Binet for mild, asymptomatic patients.
  • Cognitive testing [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    A retrospective review of cases indicates that language delay and cognitive regression are the earliest manifestations of the disease. The investigators will perform Mullen scales of Early learning for mild to moderate patients.
  • Language Delay [ Time Frame: Baseline, 6 months, 12 months, 24 months ]
    The investigators will use the Preschool Language scale -5 to monitor language.
  • Visual Failure [ Time Frame: ERG: Baseline, Day 30, 12 months, 24 months OCT: Baseline and 24 months ]
    This will be assessed via electroretinograms (ERG) or ocular computerized tomography.
  • EEG Monitoring [ Time Frame: Baseline, 12 months, 24 months ]
    24 hour EEG long term monitoring to monitor progression of encephalopathy and epileptiform activity.


Original Secondary Outcome: Same as current

Information By: Nationwide Children's Hospital

Dates:
Date Received: March 16, 2016
Date Started: March 2016
Date Completion: March 2019
Last Updated: March 28, 2017
Last Verified: March 2017