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

NCT04903288 | Active Not Recruiting Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: PTC-AADC-GT-002
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

AADC Deficiency

Keywords

AADC Deficiency gene therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Change From Baseline in Neurotransmitter Cerebrospinal Fluid (CSF) Metabolite HVA at Week 48

  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)

  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

  Baseline (Day 1), Weeks 8 and 48

• Number of Participants Who Attain Motor Milestones

  Baseline (Day 1) up to Week 260

• Change in Peabody Developmental Motor Scale, Second Edition (PDMS-2)

  Baseline (Day 1), Week 260

Study Arms (1)

Eladocagene Exuparvovec

EXPERIMENTAL

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

Interventions

Eladocagene Exuparvovec GENETIC

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.

Also known as: KEBILIDI™

Eladocagene Exuparvovec

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (6)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Duke University Hospital

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Chaim Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

National Taiwan University Hospital, Department of Pediatrics and Medical Genetics

Taipei, 10041, Taiwan

Location

MeSH Terms

Conditions

Aromatic amino acid decarboxylase deficiency

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: May 12, 2021
• Primary Completion: May 22, 2023
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 24, 2026
• Results First Posted: January 1, 2025

Record last verified: 2026-04

Locations

TW (1); IL (1); US (4)