A Study of SmartFlow Magnetic Resonance (MR) Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Participants

An Open-Label Trial to Address the Safety of the SmartFlow MR-Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Subjects

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 Overview

• Status: Active, not recruiting
• Conditions: AADC Deficiency
• Intervention / Treatment: Genetic: Eladocagene Exuparvovec

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center
• Taiwan
  • Taipei, Taiwan, 10041
    • National Taiwan University Hospital, Department of Pediatrics and Medical Genetics
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pediatric participants must have genetically-confirmed AADC deficiency with typical clinical characteristics and decreased AADC enzyme activity in plasma.
• Cranium sufficiently developed to allow placement of ClearPoint® system for stereotactic surgery.
• Persistent neurological defects secondary to AADC deficiency despite standard medical therapy (dopamine agonists, monoamine oxidase inhibitor, pyridoxine, or other forms of vitamin B6) in the opinion of the investigator.
• Unable to ambulate independently (with or without assistive device).
• Baseline hematology, chemistry, and coagulation values within the normal pediatric laboratory value ranges, unless in the investigator's opinion the out of range values are not clinically significant with respect to the participant's suitability for surgery.
• Participant must test negative for coronavirus disease of 2019 (COVID-19) a maximum of 72 hours prior to receiving gene therapy.
• Participant must be on stable dosage for 3 months prior to baseline for all medications related to treatment of AADC deficiency, including dopamine agonists, monoamine oxidase inhibitors, anticholinergic drugs, and vitamin B6.
• Females of childbearing potential must have a negative pregnancy test at screening and baseline and agree to abstinence or double-barrier form of contraception for the duration of the study following discharge from the hospital (acceptable methods will be determined by the site).
• Males sexually active with females of childbearing potential must agree to use a barrier method of birth control during the study following discharge from the hospital.
• Parent(s)/legal guardian(s) of the participant 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 the participant must give their consent for the participant to enroll in the study.

Exclusion Criteria:

• The participant has presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk.
• Participants with pyridoxine 5'-phosphate oxidase or tetrahydrobiopterin (BH4) deficiency.
• Contraindication for imaging studies (computed tomography [CT] scan, PET or magnetic resonance imaging [MRI]), including sedation limitations or metal that would interfere with a brain MRI.
• Anti-adeno-associated virus, serotype 2 (anti-AAV2) antibody titer higher than 1:1200 or >1 optical density value by enzyme-linked immunosorbent assay.
• Participants who have received treatment with other experimental therapies within the last 24 weeks prior to planned gene therapy administration, or any treatment ever with a gene therapy.
• Evidence of a clinically active infection.
• Females who are pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eladocagene Exuparvovec; Participants will receive eladocagene exuparvovec intraoperatively at 1.8×10^11 vector genomes (vg) via SmartFlow® MR Compatible Ventricular Cannula in a single operative session. Participants will receive standard of care for their AADC deficiency during the study.	Genetic: Eladocagene Exuparvovec; 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.; Other Names: KEBILIDI™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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."	Baseline (Day 1) up to Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
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)	Baseline (Day 1), Week 8, Week 48
Change From Baseline in Neurotransmitter Cerebrospinal Fluid (CSF) Metabolite HVA at Week 48	Baseline (Day 1), Week 48
Change in Peabody Developmental Motor Scale, Second Edition (PDMS-2)	Baseline (Day 1), Week 260
Change in Bayley Scale of Infant Development, Third Edition (Bayley-III)	Baseline (Day 1), Week 260
Change in EuroQol-5 Dimensions Youth Version (EQ-5D-Y)	Baseline (Day 1), Week 260
Change in Body Weight	Baseline (Day 1), Week 260
Number of Participants With AADC-Specific Symptoms	Baseline (Day 1) up to Week 260
Change From Baseline in Neurotransmitter CSF Metabolites 5-hydroxyindoleacetic Acid (5-HIAA), and 3-O-methyldopa (3-OMD) at Weeks 8 and 48	Baseline (Day 1), Weeks 8 and 48
Number of Participants Who Attain Motor Milestones	Baseline (Day 1) up to Week 260
"Number of Participants With Treatment-Emergent Adverse Events (TEAEs) "	Baseline (Day 1) up to Week 260

Collaborators and Investigators

• Sponsor: PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): May 22, 2023
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: AADC Deficiency gene therapy
• Additional Relevant MeSH Terms: Aromatic amino acid decarboxylase deficiency
• Other Study ID Numbers: PTC-AADC-GT-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes