A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC
Information source: National Taiwan University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Aromatic L-amino Acid Decarboxylase (AADC) Deficiency
Intervention: gene therapy (Genetic)
Phase: Phase 1/Phase 2
Status: Enrolling by invitation
Sponsored by: National Taiwan University Hospital Official(s) and/or principal investigator(s): Wuh-Liang Hwu, MD, Principal Investigator, Affiliation: Department of Pediatrics and Medical Genetics, National Taiwan University Hospital
Summary
This Phase I/II trial is to prove the efficacy and safety of AAV2-hAADC to treat patients
with AADC deficiency.
Clinical Details
Official title: A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: efficacy of the intervention(s)
Secondary outcome: Safety of the trialOther secondary efficacy end points Exploratory end points
Detailed description:
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.
Eligibility
Minimum age: 24 Months.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. A definitive diagnosis of AADC deficiency, including a CSF study showing decreased
levels of HVA and 5-HIAA, and an elevated L-dopa level, and the presence of at least
one AADC gene pathologic mutation.
2. The patient must have clinical symptoms of AADC deficiency, include hypotonia,
dystonia, and oculogyric crisis.
3. The patient must be older than 24 months of age or has skull bones suitable for
surgery.
4. The parents of study participants must agree to comply in good faith with the
required baseline and follow-up assessments.
5. The parents or guardians must understand and sign their child's informed consent
form.
Exclusion criteria
1. Other significant medical or neurological conditions which would create an
unacceptable operative risk. Each case will be individually reviewed and the final
decision shall rest with the Primary Investigator.
2. Preexisting immunity to AAV may limit AAV-mediated gene delivery. Patients with
anti-AAV2 antibody titer higher than 1. 0 OD will be excluded.
3. The patient cannot take medicines that will alter the effect of this clinical trial.
Locations and Contacts
National Taiwan University Hospital, Taipei 100, Taiwan
Additional Information
literature search for AADC deficiency
Starting date: August 2014
Last updated: December 2, 2014
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