Clinical Trial: A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion

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

Official Title: A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion

Brief Summary: This clinical trial expansion is to offer patients, who are not enrolled into the Phase I/II trial, a chance of treatment, to extend the experience in this gene therapy, and to increase the dosage slightly to waive the drug dilution procedure.

Detailed Summary: Methods: AAV2-hAADC viral vector has been produced by a GMP facility. Single dose toxicity test for AAV2-hAADC in rat has been competed by a GLP facility which revealed no acute toxicity. Viral vector will be injected directly to bilateral putamens by stereotactic surgery. The safety of the surgery will be monitored by both computed tomography (CT) and magnetic resonance imaging (MRI). Efficacy of the treatment will be monitored by positron emission tomography (PET), cerebral spinal fluid (CSF) neurotransmitter levels, and motor and mental developmental scales.Expected achievement: Since motor dysfunction causes the major morbidity in patients with AADC deficiency, restore of AADC activity in the putamens should relieve their motor symptoms, as demonstrated by our compassionate treatment. This study is the only chance of treatment for patients with AADC deficiency. The investigators expect a high chance to complete this trial and then proceed to the drug approval Phase III pivotal trial. The conduction of a clinical trial on human gene therapy will also trigger the advance of biotechnology in Taiwan.
Sponsor: National Taiwan University Hospital

Current Primary Outcome:

  • Measurable neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy. [ Time Frame: 13 months ]
  • Increase of PDMS-II score more than 10 points one year after gene therapy [ Time Frame: 13 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Post-surgery intracerebral hemorrhage [ Time Frame: 13 months ]
  • Post-surgery CSF leakage [ Time Frame: 13 months ]
  • Severity of post-gene therapy dyskinesia (if NG tube feeding is required) [ Time Frame: 13 months ]
  • Incidence of other SAE (we will collect all AEs and their severity information, including treatment-emergent adverse events) [ Time Frame: 13 months ]


Original Secondary Outcome: Same as current

Information By: National Taiwan University Hospital

Dates:
Date Received: October 3, 2016
Date Started: September 2016
Date Completion: December 2018
Last Updated: October 5, 2016
Last Verified: October 2016