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
Genetic: gene therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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(s) [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]
- 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: Post-operative day 0, days 3~7, months 3, 6, 9, 12 ] [ Designated as safety issue: Yes ]
- Post-surgery intracerebral hemorrhage
- Post-surgery CSF leakage
- Severity of post-gene therapy dyskinesia (if NG tube feeding is required)
- Other secondary efficacy end points [ Time Frame: Post-operative months 3, 6, 9, 12 (BW & developmental tests) ; day 0, 12th month (PET) ] [ Designated as safety issue: No ]
- Body weight gain
- Increase putaminal signal in DOPA-PET study
- Increase of score in other developmental tests
- Exploratory end points [ Time Frame: Baseline, months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
- Correlation between anti-AAV2 titer and efficacy
- Correlation between age and efficacy
|Study Start Date:||August 2014|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
Genetic: 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|