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 : August 11, 2021
|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, 2021|
|Estimated Study Completion Date :||December 31, 2021|
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
- Evaluation of therapeutic effect [ Time Frame: 12 months ]
- At one year post-surgery, neurotransmitter metabolites (HVA or HIAA) is detectable in CSF (higher than that at pre-surgery)
- At one year post-surgery, PDMS-II score is higher than that at pre-surgery, with an improvement over 10 points
- Evaluation of safety and other therapeutic effects Evaluation for the treatment safety [ Time Frame: 12 months ]
- The absence of intracranial bleeding, which requires surgical management, after the surgery
- Craniotomy-induced CSF exudation
- The severity of post-surgery hyperactivity (if feeding is affected and then nasogastric tube is needed)
- Incidence of other severe adverse events (information of adverse events of all kinds and severities will be collected, including treatment-emergent adverse events).
- Evaluation of secondary therapeutic effects [ Time Frame: 5 years ]
- Weight gain
- Increased signal intensity of dopamine in putamen during PET imaging
- Increased score in other development evaluations
- Exploratory endpoint [ Time Frame: 5 years ]
- The correlation between anti-AAV2 titer and therapeutic effect
- The correlation between subject's age and therapeutic effect
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, M.D., Ph.D.||National Taiwan University Hospital|