Eladocagene Exuparvovec for AADC Deficiency

Recruiting at 7 trial locations

Overseen By Patient Advocacy

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: PTC Therapeutics

Must be taking: Dopamine agonists, Monoamine oxidase inhibitors

Disqualifiers: Significant medical conditions, Pyridoxine 5'-phosphate oxidase deficiency, Tetrahydrobiopterin deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called eladocagene exuparvovec, a gene therapy for children with AADC deficiency, a rare genetic disorder affecting movement and development. The main goals are to evaluate how the treatment functions in the body and its safety. Eligible children have confirmed AADC deficiency and experience movement difficulties despite current treatments. Researchers will use a special device to deliver the treatment and monitor its effects over time. Participants will also continue their usual care during the study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial requires that participants stay on a stable dosage of their current medications related to AADC deficiency for at least 3 months before starting the trial.

What prior data suggests that the SmartFlow® MR Compatible Ventricular Cannula is safe for administering eladocagene exuparvovec?

Research has shown that eladocagene exuparvovec is generally safe for treating AADC deficiency, a rare genetic disorder affecting the nervous system. In studies with patients who received this treatment, no therapy-related deaths occurred. Reports also indicate improvements in symptoms such as movement skills and body weight. While some side effects may occur, patients usually tolerate the treatment well. Based on current data, eladocagene exuparvovec is considered safe for individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Eladocagene Exuparvovec is unique because it offers a gene therapy approach for AADC deficiency, which is a departure from the standard treatments like dopamine agonists and vitamin B6 supplements. Unlike these treatments, which manage symptoms, Eladocagene Exuparvovec targets the root cause by delivering a functional gene directly into the brain to restore enzyme production. This innovative delivery method using a SmartFlow® MR Compatible Ventricular Cannula is designed to provide long-term benefits from a single treatment session, which has researchers excited about its potential to significantly improve patient outcomes.

What evidence suggests that eladocagene exuparvovec might be an effective treatment for AADC deficiency?

Research has shown that eladocagene exuparvovec, the treatment under study in this trial, can help patients with AADC deficiency live longer and improve their quality of life. AADC deficiency is a rare condition that affects movement and development. Patients who received this treatment showed better results than those who received usual care. This gene therapy addresses the disorder's main issue by helping the body produce more of the chemicals needed for normal brain function. Early findings suggest that while some patients might experience mild to moderate movement issues, these typically resolve within a few months. Overall, this treatment appears promising in alleviating the symptoms of AADC deficiency. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for pediatric patients with AADC deficiency who can't walk independently, have a developed cranium for surgery, and are on stable medication. They must test negative for COVID-19 and not be pregnant or breastfeeding. Participants need normal blood tests unless deemed okay by the investigator, and parents must consent to study requirements.

Inclusion Criteria

I cannot walk on my own, even with help from devices.

I tested negative for COVID-19 within the last 72 hours before gene therapy.

My child has a confirmed genetic AADC deficiency with typical symptoms and low enzyme levels.

Exclusion Criteria

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

I have a deficiency in pyridoxine 5'-phosphate oxidase or BH4.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Trial Phase

Participants receive eladocagene exuparvovec treatment and safety of the SmartFlow MR-Compatible Ventricular Cannula is assessed

8 weeks

Single operative session

Extension Phase

Capture additional clinical information for eladocagene exuparvovec through study evaluations, changes in motor development, AADC-specific symptoms, and other PD measures

Not specified

Long-term Extension Phase

Capture long-term safety and efficacy data from participants treated with eladocagene exuparvovec

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Eladocagene Exuparvovec

Trial Overview The trial studies Eladocagene Exuparvovec administered via SmartFlow® MR Compatible Ventricular Cannula in children with AADC deficiency. It aims to evaluate the drug's effects on HVA levels during different phases: initial treatment, extended monitoring of clinical changes, and long-term safety/effectiveness.

How Is the Trial Designed?

Group I: Eladocagene Exuparvovec Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

PTC Therapeutics

Lead Sponsor

Trials

75

Recruited

6,300+

Dr. Matthew B. Klein

PTC Therapeutics

Chief Executive Officer since 2023

BA from the University of Pennsylvania, MD from Yale University School of Medicine, MS in Epidemiology from the University of Washington School of Public Health

Dr. Stuart W. Peltz

PTC Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37803205/

Long-Term Outcomes of Eladocagene Exuparvovec ... Patients treated with eladocagene exuparvovec were found to have improved survival and quality of life benefits compared to patients treated with BSC.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10611606/

Long-Term Outcomes of Eladocagene Exuparvovec ... Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare disease with symptoms including movement disorders, developmental delays, and ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2831389

Eladocagene Exuparvovec for Aromatic L-Amino Acid ... This JAMA Insights discusses the US Food and Drug Administration approval of Kebilidi, eladocagene exuparvovec, for the treatment of ...

4. link.springer.com link.springer.com/article/10.1007/s40273-025-01542-8

Eladocagene Exuparvovec for the Treatment of Aromatic l- ... Aromatic l-amino acid decarboxylase deficiency (AADCd) is a rare, neurometabolic disorder caused by an autosomal recessive mutation in the dopa ...

5. cell.com cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(21)00576-1

Long-term efficacy and safety of eladocagene exuparvovec ... Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8822132/

Long-term efficacy and safety of eladocagene exuparvovec ... Eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.

7. anthem.com anthem.com/medpolicies/abcbs/active/mp_pw_e003376.html

MED.00151 Gene Therapy for Aromatic L-Amino Acid ... Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022; 30(2):509-518. Wassenberg T ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000203196

Eladocagene Exuparvovec Gene Therapy Improves Motor ... Investigate the efficacy and safety of eladocagene exuparvovec in patients with aromatic l-amino acid decarboxylase deficiency (AADCd).

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324921001523

88 safety and improved efficacy outcomes in children with ... In children with AADC deficiency who received eladocagene exuparvovec gene therapy, body weight increased and oculogyric crises and dyskinesia improved.