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NCT Number: NCT04903288

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

AADC Deficiency Aromatic amino acid decarboxylase deficiency

Age range

1 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Chaim Sheba Medical Center, Ramat Gan, Israel

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: KEBILIDI™

Primary outcomes

  1. Change From Baseline in HVA Metabolite Level at the End of the Trial Phase

    Time frame: Baseline (Day 1), Week 8

    HVA is a main metabolite of dopamine and HVA CSF levels are recognized as a proxy for dopamine levels in the brain.

  2. Number of Participants With Adverse Events (AEs) Associated With the Surgical Administration of Eladocagene Exuparvovec Using the SmartFlow® MR-Compatible Ventricular Cannula

    Time frame: Baseline (Day 1) up to Week 8

    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."

Secondary outcomes

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

    Time frame: Baseline (Day 1), Week 48

  2. 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

  3. 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

  4. Number of Participants Who Attain Motor Milestones

    Time frame: Baseline (Day 1) up to Week 260

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

    Time frame: Baseline (Day 1), Week 260

  6. Change in Bayley Scale of Infant Development, Third Edition (Bayley-III)

    Time frame: Baseline (Day 1), Week 260

  7. Change in EuroQol-5 Dimensions Youth Version (EQ-5D-Y)

    Time frame: Baseline (Day 1), Week 260

  8. Change in Body Weight

    Time frame: Baseline (Day 1), Week 260

  9. Number of Participants With AADC-Specific Symptoms

    Time frame: Baseline (Day 1) up to Week 260

  10. "Number of Participants With Treatment-Emergent Adverse Events (TEAEs) "

    Time frame: Baseline (Day 1) up to Week 260

Sponsors and collaborators

Lead sponsor

PTC Therapeutics

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2023
Study completion
2028
First posted
May 26, 2021
Registry last updated
Apr 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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