This study will have a trial phase, extension phase, and a long-term extension phase. The primary objectives of the trial phase are to assess the pharmacodynamics (PD) of eladocagene exuparvovec treatment by evaluation of homovanillic acid (HVA) levels and to assess the safety of the SmartFlow® magnetic resonance (MR) Compatible Ventricular Cannula for administering eladocagene exuparvovec to pediatric participants with aromatic L-amino acid decarboxylase (AADC) deficiency. The extension phase is designed to capture additional clinical information for eladocagene exuparvovec through study evaluations, changes in motor development, AADC-specific symptoms, and other PD measures. The long-term extension phase is designed to capture long-term safety and efficacy data from participants treated with eladocagene exuparvovec.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Four 0.08 milliliters (mL) infusions at a dose of 0.45×10\^11 vg and a volume of 80 microliters (μl) per site to 4 sites (2 per putamen), for the total dose of 1.8×10\^11 vg and a total volume of 320 μl per participant.
Boston Children's Hospital
Boston, Massachusetts, United States
Duke University Hospital
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Texas Children's Hospital
Houston, Texas, United States
Chaim Sheba Medical Center
Ramat Gan, Israel
National Taiwan University Hospital, Department of Pediatrics and Medical Genetics
Taipei, Taiwan
Change From Baseline in HVA Metabolite Level at the End of the Trial Phase
HVA is a main metabolite of dopamine and HVA CSF levels are recognized as a proxy for dopamine levels in the brain.
Time frame: Baseline (Day 1), Week 8
Number of Participants With Adverse Events (AEs) Associated With the Surgical Administration of Eladocagene Exuparvovec Using the SmartFlow® MR-Compatible Ventricular Cannula
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered related to the drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease in a study participant who was administered gene therapy in this study. Number of participants with AEs related to the SmartFlow MR-compatible ventricular cannula used to administer eladocagene exuparvovec to pediatric participants at the end of Trial Phase (8 weeks after administration) are reported. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module."
Time frame: Baseline (Day 1) up to Week 8
Change From Baseline in Neurotransmitter Cerebrospinal Fluid (CSF) Metabolite HVA at Week 48
Time frame: Baseline (Day 1), Week 48
Change From Baseline in Positron Emission Tomography (PET) Imaging of Putaminal-Specific L-6-[18F] Fluoro-3,4-Dihydroxyphenylalnine (18F-DOPA) PET Uptake at the End of the Trial Phase (Week 8) and the Extension Phase (Week 48)
Time frame: Baseline (Day 1), Week 8, Week 48
Change From Baseline in Neurotransmitter CSF Metabolites 5-hydroxyindoleacetic Acid (5-HIAA), and 3-O-methyldopa (3-OMD) at Weeks 8 and 48
Time frame: Baseline (Day 1), Weeks 8 and 48
Number of Participants Who Attain Motor Milestones
Time frame: Baseline (Day 1) up to Week 260
Change in Peabody Developmental Motor Scale, Second Edition (PDMS-2)
Time frame: Baseline (Day 1), Week 260
Change in Bayley Scale of Infant Development, Third Edition (Bayley-III)
Time frame: Baseline (Day 1), Week 260
Change in EuroQol-5 Dimensions Youth Version (EQ-5D-Y)
Time frame: Baseline (Day 1), Week 260
Change in Body Weight
Time frame: Baseline (Day 1), Week 260
Number of Participants With AADC-Specific Symptoms
Time frame: Baseline (Day 1) up to Week 260
"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) "
Time frame: Baseline (Day 1) up to Week 260
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