Clinical Trial: A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC

Brief Summary: This Phase I/II trial is to prove the efficacy and safety of AAV2-hAADC to treat patients with AADC deficiency.

Detailed Summary:

Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a rare genetic disorder. Taiwanese carry a high prevalence of AADC deficiency due to the founder mutation IVS6+4 A>T, and patients usually die before the age 5-6 years due to severe motor dysfunction.

Gene therapy with adeno-associated virus (AAV) serotype 2 (AAV2) driven human AADC (hAADC) has been tested in both animal models and Phase I clinical trials of Parkinson disease. We have done a compassionate treatment of 8 patients with AADC deficiency by AAV2-hAADC and demonstrated a result that among the treated patients, 4 could stand with support, 3 could sit with support, and there was no virus-associated toxicity. The longest follow up has exceeded 4 years.

This study is to prove the safety and efficacy of AAV2-hAADC treatment for patients with Aromatic L-amino acid decarboxylase (AADC) deficiency.


Sponsor: National Taiwan University Hospital

Current Primary Outcome: Efficacy of the intervention [ Time Frame: 13 months ]

  1. Measurable neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy.
  2. Increase of PDMS-II score more than 10 points one year after gene therapy


Original Primary Outcome: post-operative intracerebral bleeding [ Time Frame: Post-operative day 0 (CT) and day 3 (MRI) ]

Number of patients with detectable intracerebral bleeding Number of patients with serious intracerebral bleeding that requires surgical management


Current Secondary Outcome: Safety of the trial [ Time Frame: 12 months ]

  1. Post-surgery intracerebral hemorrhage
  2. Post-surgery CSF leakage
  3. Severity of post-gene therapy dyskinesia (if NG tube feeding is required)
  4. Incidence of other SAE (we will collect all AEs and their severity information, including treatment-emergent adverse events)


Original Secondary Outcome:

  • Motor development [ Time Frame: 12th month post surgery ]
    Number of patients showing improvement of PDMS-2 score
  • CSF neurotransmitter [ Time Frame: 12th month post surgery ]
    Number of patients showing an increase in CSF neurotransmitter concentration


Information By: National Taiwan University Hospital

Dates:
Date Received: June 12, 2011
Date Started: October 1, 2014
Date Completion:
Last Updated: May 16, 2017
Last Verified: May 2017