A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC (AADC)
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|ClinicalTrials.gov Identifier: NCT01395641|
Recruitment Status : Active, not recruiting
First Posted : July 15, 2011
Last Update Posted : October 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Aromatic L-amino Acid Decarboxylase (AADC) Deficiency||Drug: gene therapy||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC|
|Actual Study Start Date :||October 1, 2014|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01395641
|National Taiwan University Hospital|
|Taipei, Taiwan, 100|
|Principal Investigator:||Wuh-Liang Hwu, MD||Department of Pediatrics and Medical Genetics, National Taiwan University Hospital|