Aromatic L-amino Acid Decarboxylase Deficiency Clinical Trial
Official title:
An Open, Dose-escalating and Dose Confirmation Trial to Evaluate the Safety and Efficacy of VGN-R09b by Intra Putamen Injection in Patients With Severe Aromatic L-amino Acid Decarboxylase (AADC) Deficiency
This trial includes dose-escalating part (phase 1) and dose confirming part, to prove the safety and efficacy of VGN-R09b to treat patients with severe AADC deficiency
Status | Not yet recruiting |
Enrollment | 16 |
Est. completion date | September 2030 |
Est. primary completion date | June 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Months to 8 Years |
Eligibility | Inclusion Criteria: 1. The child patient has to be =18 months old and < 8 years old, and a head circumference big enough for surgery as judged by investigator. 2. Historical diagnosis of AADC deficiency with clinical symptoms consistency, AND with Molecular genetic confirmation of homozygous or compound heterozygous mutation point of IVS6+4A>T in DDC gene. 3. With Plasma AADC activity less than or equal to 12 pmol/min/mL. 4. Motor development at baseline <3 months (head fully uncontrollable at baseline), and Failed to benefit from standard medical therapy (dopamine agonists, monoamine oxidase inhibitor or related form of Vitamin B6) at discretion of investigators. 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. Contraindication to sedation during surgery or imaging studies (PET or MRI). |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Shanghai Vitalgen BioPharma Co., Ltd. |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Adverse Events (AEs), Serious Adverse Events (SAEs) | Vital signs, physical examination, laboratory test will be monitored after drug injection | up to Week 52 | |
Primary | Number of subjects who achieved motor development milestones | Four milestones, including Head control, Sit independently, Stand/stepping with support, Walk with minimal assistant, would be assessed according to definition in Peabody Developmental Motor Scale 2nd edition (PDMS-2). Each milestone would be scored as 0, 1 or 2, and score 2 means achievement of the milestone. | up to 24 months | |
Secondary | Change in brain AADC activity | Increase in signal in the putamen and nigra on Fluorodopa-PET imaging as brain AADC activity measure | up to 5 Years | |
Secondary | Change in Cerebrospinal Fluid (CSF) neurotransmitter metabolite concentrations | Neurotransmitter metabolite concentrations of Homovanillic Acid/Hydroxyindoleacetic Acid (HVA/5-HIAA) would be measured | up to 5 Years | |
Secondary | Change from baseline in motor function | Motor function would be assessed by Peabody Developmental Motor Scale 2nd edition (PDMS-2). The score ranges from 0 to 482, and higher score means the better in motor function. | up to 5 Years | |
Secondary | Change in number of Clinical symptoms | Number of disease related symptoms | up to 5 Years | |
Secondary | Viral shedding | Concentrations of Viral genome in serum/urine would be measured | up to 1 week | |
Secondary | Immunogenicity after injection | Subject number with positive antibodies of AAV9/AADC/Glial Cell Line-Derived Neurotrophic Factor (GDNF) in blood would be reported | up to 26 weeks | |
Secondary | Number of Adverse Events (AEs), Serious Adverse Events (SAEs) in Long-term follow-up | Drug-related AEs and SAEs would be monitored as long as 5 years after injection | up to 5 Years |
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