A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC (AADC)
|Aromatic L-amino Acid Decarboxylase (AADC) Deficiency||Drug: gene therapy||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC|
- Efficacy of the intervention [ Time Frame: 13 months ]
- Measurable neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy.
- Increase of PDMS-II score more than 10 points one year after gene therapy
- Safety of the trial [ Time Frame: 12 months ]
- Post-surgery intracerebral hemorrhage
- Post-surgery CSF leakage
- Severity of post-gene therapy dyskinesia (if NG tube feeding is required)
- Incidence of other SAE (we will collect all AEs and their severity information, including treatment-emergent adverse events)
- Other secondary efficacy endpoints [ Time Frame: 13 months ]
- Body weight gain
- Increase putaminal signal in F-DOPA PET study
- Increase of score in other developmental tests
- Exploratory endpoint [ Time Frame: 13 months ]
- Correlation between anti-AAV2 titer and efficacy
- Correlation between age and efficacy
|Actual Study Start Date:||October 1, 2014|
|Study Completion Date:||December 2, 2016|
|Primary Completion Date:||December 2, 2016 (Final data collection date for primary outcome measure)|
Experimental: Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
Drug: gene therapy
AAV2-hAADC viral vector will be injected into bilateral putamen by stereotactic surgery.
Other Name: Intracerebral infusion of AAV2-hAADC viral vector
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01395641
|National Taiwan University Hospital|
|Taipei, Taiwan, 100|
|Principal Investigator:||Wuh-Liang Hwu, MD||Department of Pediatrics and Medical Genetics, National Taiwan University Hospital|