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AADC DeficiencyPhase 1AADCNCT02852213

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

A Phase 1 study testing AAV2-hAADC in people with AADC Deficiency, run by Krzysztof Bankiewicz at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 24 months and older
Conditions the study is for
AADC Deficiency
What is being tested?
AAV2-hAADC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
3 sitesUnited States
Study dates
1 Jul 2016to Aug 2037
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 24 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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 24 months and older.
  • Failed to derive adequate benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor, pyridoxine or related form of Vitamin B6), as judged by presence of residual oculugyric crises and developmental delay.
  • Documented history of motor developmental delay, with inability to walk independently without support by age 18 months.
  • Cranium sufficiently developed, with sutures closed, to enable surgical placement of SmartFrame® system on the head 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.
Show all 9Show fewer
  • 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.
  • Both parents (or legal guardians) must give their consent for their child's participation in the study parents unless (i.) one parent is deceased, unknown or incompetent; (ii.) one parent is not reasonably available; or (iii.) one parent has responsibility for the care and custody of the child (if consistent with state law).
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Andrea Davis, MS contact

614-688-6412

andrea.davis@osumc.edu

United States3 sites, 3 recruiting

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

    Hannah Lehmann, hannah.lehmann@nationwidechildrens.org

    Margaret Carey, margaret.carey@nationwidechildrens.org

    Recruiting

  • The Ohio State University Medical Center

    Columbus, Ohio, 43221

    Andrea Davis, MS, 614-814-6871, andrea.davis@osumc.edu

    Russell Lonser, MD

    Recruiting

  • University of California San Francisco, Benioff Children's Hospital

    San Francisco, California, 94143

    Catalina Pen, catalina.pen@ucsf.edu

    E

    Recruiting

Other trials in United States

About this study

Official title: SIngle-Stage, Open-Label, Safety and Efficacy Study of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase by Magnetic Resonance MR-guided Infusion Into Midbrain in Pediatric Patients With AADC Deficiency

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.

Read the detailed description

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.
Conditions
AADC Deficiency
Being tested
AAV2-hAADC
Keywords
AADC, gene therapy
Medical subject headings
Aromatic amino acid decarboxylase deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAV2-hAADCDrug

    Also called Adeno Virus Human Aromatic L-Amino Acid Decarboxylase

    Initially, subjects will be enrolled sequentially into 2 dose groups. 3 subjects will be enrolled in Cohort 1 and treated with a single dose of AAV2 hAADC (1.3x10 11 vg, delivered as infusate volume of up to 160μL of vector at concentration of 8.3x10 11 vg/mL) on Day 0. Enrollment in Cohort 2 may commence after the last subject in Cohort 1 is treated and followed through Month 3 post-op, with approval of the data safety monitoring board (DSMB). Cohort 2 will receive a higher dose (4.2 x 10^11 vg, 160 uL). Upon DSMB review of Cohort 1/2 results, Cohort 3 (4-12 yo) and 4 (aged >/= 13 yo) will be dosed (1.6 x 10^12 vg, 60uL) in 1-2 sites bilaterally in-between the SNc and VTA. Cohort 5 will follow (aged 24-47 months) at 1.3 x 10^12 vg, 500uL. Final safety and clinical outcome assessments will be performed 1 year post-surgery. Follow-up analysis will be performed for 2 years post-op. Subjects will be enrolled in a long-term follow-up study to assess safety and clinical status updates.

Study groups in NCT02852213
Study groupRoleWhat they receive
Single treatment armExperimentalSingle-stage dose-escalation, open-label safety study of AAV2-hAADC delivered by image-guided convection-enhanced delivery bilaterally into the substantia nigra pars compacta and the ventral tegmental area of pediatric patients with AADC deficiency. Primary aim is to determine the dose for future studies based on safety, biomarkers of pharmacological activity of AADC and clinical outcomes. Cohort 1 (3 subjects) will receive a single low dose of AAV2 hAADC. The total AAV2-hAADC dose will be infused via MR guided infusion into 4 sites in both the left and right SNc and VTA. Dose intervals will be 90 days between the first 3 subjects. Cohort 2 dose (4 subjects) will be determined by Cohort 1 results. Following Cohort 2, Cohort 3/4 will be dose and divided divided by age. Cohorts 3/4 will receive the same dose by MR guided infusion to 1-2 sites bilaterally in-between the SNc and VTA. Cohort 5 (24-47mo old) will have same vector concentration and lower volume of infusion than Cohorts 3/4
Receives: Drug: AAV2-hAADC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events related to surgery and gene transfer

    Assessment of adverse events related to surgery (including intracerebral hemorrhage or stroke, CNS infection) and gene transfer (including severity of post-operative dyskinesia)

    Measured: 2 years

  2. CSF neurotransmitter metabolite concentrations

    Change in CSF neurotransmitter metabolite concentrations after gene transfer (increase in homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and elevated 3-O-methyldopa (3-OMD) concentrations)

    Measured: 1 year

Secondary outcomes (3)

  1. Gross Motor Function Measure

    Increase in Gross Motor Function Measure-88 (GMFM-88) score

    Measured: 2 years

  2. Symptom Diary created by PI

    Decrease in frequency and severity of oculogyric episodes

    Measured: 1 years

  3. Fluorodopa PET scan

    Increase in signal in the striatum on FDOPA-PET imaging as brain AADC activity measure

    Measured: Evaluated at 3 months and 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study start1 Jul 2016
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completionAug 2037 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02852213
Sponsor's protocol ID
2018H0269
Acronym
AADC
Status last verified
Jul 2026
First submitted
20 Jul 2016
Last updated
27 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The investigators will share pertinent information with the subjects care team such that standard of care for the subject can be maintained.

Publications

  • Brun L, Ngu LH, Keng WT, Ch'ng GS, Choy YS, Hwu WL, Lee WT, Willemsen MA, Verbeek MM, Wassenberg T, Regal L, Orcesi S, Tonduti D, Accorsi P, Testard H, Abdenur JE, Tay S, Allen GF, Heales S, Kern I, Kato M, Burlina A, Manegold C, Hoffmann GF, Blau N. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010 Jul 6;75(1):64-71. doi: 10.1212/WNL.0b013e3181e620ae. Epub 2010 May 26.

    PubMed 20505134

  • Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, VanBrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology. 2009 Nov 17;73(20):1662-9. doi: 10.1212/WNL.0b013e3181c29356. Epub 2009 Oct 14.

    PubMed 19828868

  • Fiandaca MS, Varenika V, Eberling J, McKnight T, Bringas J, Pivirotto P, Beyer J, Hadaczek P, Bowers W, Park J, Federoff H, Forsayeth J, Bankiewicz KS. Real-time MR imaging of adeno-associated viral vector delivery to the primate brain. Neuroimage. 2009 Aug;47 Suppl 2(Suppl 2):T27-35. doi: 10.1016/j.neuroimage.2008.11.012. Epub 2008 Nov 27.

    PubMed 19095069

  • Hwu WL, Muramatsu S, Tseng SH, Tzen KY, Lee NC, Chien YH, Snyder RO, Byrne BJ, Tai CH, Wu RM. Gene therapy for aromatic L-amino acid decarboxylase deficiency. Sci Transl Med. 2012 May 16;4(134):134ra61. doi: 10.1126/scitranslmed.3003640.

    PubMed 22593174

  • Caviness VS Jr, Kennedy DN, Richelme C, Rademacher J, Filipek PA. The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images. Cereb Cortex. 1996 Sep-Oct;6(5):726-36. doi: 10.1093/cercor/6.5.726.

    PubMed 8921207

  • Dumas HM, Fragala-Pinkham MA. Concurrent validity and reliability of the pediatric evaluation of disability inventory-computer adaptive test mobility domain. Pediatr Phys Ther. 2012 Summer;24(2):171-6; discussion 176. doi: 10.1097/PEP.0b013e31824c94ca.

    PubMed 22466386

  • Dumas HM, Fragala-Pinkham MA, Haley SM, Ni P, Coster W, Kramer JM, Kao YC, Moed R, Ludlow LH. Computer adaptive test performance in children with and without disabilities: prospective field study of the PEDI-CAT. Disabil Rehabil. 2012;34(5):393-401. doi: 10.3109/09638288.2011.607217. Epub 2011 Oct 12.

    PubMed 21988750

  • Eapen M, Zald DH, Gatenby JC, Ding Z, Gore JC. Using high-resolution MR imaging at 7T to evaluate the anatomy of the midbrain dopaminergic system. AJNR Am J Neuroradiol. 2011 Apr;32(4):688-94. doi: 10.3174/ajnr.A2355. Epub 2010 Dec 23.

    PubMed 21183619

  • Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med. 2003 May;9(5):589-95. doi: 10.1038/nm850. Epub 2003 Mar 31.

    PubMed 12669033

  • Haley, S., W. Coster, L. Ludlow, J. Haltiwanger and A. PA (1992). Pediatric Evaluation of Disability Inventory: Development, Standardization and Administration Manual. Boston, MA, Trustees of Boston University.

  • Hnasko TS, Perez FA, Scouras AD, Stoll EA, Gale SD, Luquet S, Phillips PE, Kremer EJ, Palmiter RD. Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8858-63. doi: 10.1073/pnas.0603081103. Epub 2006 May 24.

    PubMed 16723393

  • Hyland K, Clayton PT. Aromatic amino acid decarboxylase deficiency in twins. J Inherit Metab Dis. 1990;13(3):301-4. doi: 10.1007/BF01799380. No abstract available.

    PubMed 1700191

  • Hyland K, Clayton PT. Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology. Clin Chem. 1992 Dec;38(12):2405-10.

    PubMed 1281049

  • Hyland K, Surtees RA, Rodeck C, Clayton PT. Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis. Neurology. 1992 Oct;42(10):1980-8. doi: 10.1212/wnl.42.10.1980.

    PubMed 1357595

  • Jernigan TL, Archibald SL, Berhow MT, Sowell ER, Foster DS, Hesselink JR. Cerebral structure on MRI, Part I: Localization of age-related changes. Biol Psychiatry. 1991 Jan 1;29(1):55-67. doi: 10.1016/0006-3223(91)90210-d.

    PubMed 2001446

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AAV2-hAADC in people with AADC Deficiency, run by Krzysztof Bankiewicz at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Andrea Davis, MS (614-688-6412, andrea.davis@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events related to surgery and gene transfer (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02852213, which also lists 47 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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