An Early Clinical Trial to Evaluate VGN-R09b for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency.

Launched by SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE · Mar 9, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called VGN-R09b for children with a rare condition known as Aromatic L-amino Acid Decarboxylase (AADC) deficiency. This condition affects how the brain produces certain important chemicals, which can lead to serious developmental and motor challenges. The aim of this early trial is to check if VGN-R09b is safe and effective for these patients. The trial is currently looking for participants, specifically children aged 2 to 8 years old, who have been diagnosed with AADC deficiency and have not benefited from standard treatments.

To participate, children need to meet certain criteria, including having specific lab test results that confirm their diagnosis. Parents or guardians must give their consent for their child to join the study and agree to help with sharing information about the child's condition. Those who enroll can expect to receive close monitoring throughout the trial to assess the treatment's effects. It's important to know that there are specific health conditions that may exclude a child from participating, such as serious brain abnormalities or other significant medical issues. This trial represents a hopeful step forward in finding better treatments for children with AADC deficiency.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. The child patient has to be ≥2 years old and \< 8 years old, or a head circumference big enough for surgery.
• • 2. Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND confirmed by one of the lab tests: (1) CSF neurotransmitter profile demonstrating reduced HVA and 5-HIAA, and elevated L-Dopa concentrations; (2) Plasma AADC activity less than or equal to 5 pmol/min/mL, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation of IVS6+4A\>T in DDC.
• • 3. Motor development at baseline ≤3 months, and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators.
• • 4. Stable medication regimen for treatment of AADC deficiency: (i.e. no new medications introduced for at least 6 months, and no existing medication dose changes for at least 3 months prior to Baseline).
• • 5. Parent(s)/legal guardian(s) with custody of subject must give their consent for subject to enroll in the study
• • 6. Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
• Exclusion Criteria:
• • 1. Intracranial neoplasm or any structural brain abnormality or lesion (e.g., severe brain atrophy, white matter degenerative changes), which, in the opinion of the study investigators, would confer excessive risk and/or inadequate potential for benefit.
• • 2. Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive.
• • 3. Severe coagulopathy, or need for ongoing anticoagulant therapy.
• • 4. clinically active infection or with severe infection within 12 weeks before screening (e.g. adenovirus or herpes virus, pneumonia, sepsis, central nervous system infection).
• • 5. Previous stereotactic neurosurgery, or any gene/cell therapy.
• • 6. Received live vaccination within 4 weeks.
• • 7. Patients with anti-AAV9 neutralizing antibody titer over 1,200 folds.
• • 8. Contraindication to sedation during surgery or imaging studies (PET or MRI).