A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients (AADC)

  • End date
    Jan 21, 2028
  • participants needed
  • sponsor
    Krzysztof Bankiewicz
Updated on 21 March 2022


The overall objective of this study is to determine the safety and efficacy of AAV2-hAADC delivered to the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) in children with aromatic L-amino acid decarboxylase (AADC) deficiency.


The Study will specifically address:

  • Safety, as measured by adverse events (AEs), safety laboratory tests, brain imaging, and the relationship of AEs to study/surgical procedures or to AAV2 hAADC.
  • Clinical responses to treatment with AAV2-hAADC. The primary clinical outcomes will reflect the predominant motor deficits of loss of motor function and dystonic movements.

Primary Endpoints Safety: Assessment of AE or severe AE (SAE) and its relationship to study surgery, infusion, or treatment effect (graded as definite, probable, possible, unlikely or unrelated).

  • Adverse Events and Serious Adverse Events
  • Post-operative MRI and/or CT (with contrast if clinically indicated)
  • Clinical laboratory assessments (hematology, chemistry, immunology) Biological Activity: Demonstration of effective restoration of AADC function by assays of cerebrospinal fluid (CSF) neurotransmitter metabolites and 18-fluoro-3,4-dihydroxyphenylalanine (F-DOPA) positron emission tomography (PET) imaging.

Secondary and Exploratory Endpoints To obtain preliminary data for clinical response by assessing the magnitude and variability of changes in specific outcomes.

The principal clinical outcome measures are:

  • Motor function, as assessed by the Gross Motor Function Measure (GMFM-88)
  • Frequency of oculogyric episodes, as measured by a Symptom Diary

Secondary clinical outcome measures include:

• Assessment of subject disability, as assessed using the Pediatric Evaluation of Disability Inventory (PEDI); adaptive behavior, as assessed using Vineland Adaptive Behavior Scale; Patient's Global Impression of Change (PGI-C); and quality of life, as determined using the Pediatric Quality of Life Inventory (PedsQL).

Although the investigators recognize that the utility of established developmental and cognitive assessments may be limited because of the study population's severe physical disability, the investigators will use the following:

  • Peabody Developmental Motor Scales 2nd edition (PDMS-2)
  • Bayley Scales of Infant Development, 3rd edition.

Condition AADC Deficiency
Treatment AAV2-hAADC
Clinical Study IdentifierNCT02852213
SponsorKrzysztof Bankiewicz
Last Modified on21 March 2022


Yes No Not Sure

Inclusion Criteria

Definite diagnosis of AADC deficiency, confirmed by at least two of the following three criteria: (1) CSF neurotransmitter profile demonstrating reduced HVA and 5-HIAA, and elevated 3-OMD concentrations; (2) Plasma AADC activity less than or equal to 5 pmol/min/mL; (3) Molecular genetic confirmation of homozygous or compound heterozygous mutations in DDC
Age 4 years and up
Failed to derive adequate benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor, pyridoxine or related form of Vitamin B6)
Unable to ambulate independently (with or without assistive device)
Cranium sufficiently developed, with sutures closed, to enable surgical placement of SmartFrame® system on the skull for MRI-guided stereotactic targeting
Brain MRI does not show any conditions or malformations that are clinically significant with respect to risks for stereotactic brain surgery
Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including the need for frequent and prolonged follow-up
Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study
Stable medication regimen for treatment of AADC deficiency: (i.e. no new medications introduced for at least 6 months, and no existing medication dose changes for at least 3 months prior to Baseline)
Baseline hematology, chemistry, and coagulation values within the normal pediatric laboratory value ranges, unless in the Investigator's judgment, the out of range values are not clinically significant with respect to subject's suitability for surgery

Exclusion Criteria

Intracranial neoplasm or any structural brain abnormality or lesion (e.g., severe brain atrophy, white matter degenerative changes), which, in the opinion of the study investigators, would confer excessive risk and/or inadequate potential for benefit
Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive
Previous stereotactic neurosurgery
Coagulopathy, or need for ongoing anticoagulant therapy
Contraindication to sedation during surgery or imaging studies (SPECT, PET or MRI)
Receipt of any investigational agent within 60 days prior to Baseline and during study participation
Evidence of clinically active infection with adenovirus or herpes virus on physical examination
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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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