Active, not recruiting
Phase 2/3
A Trial to Evaluate Safety and Efficacy of a Product Named VGN-R09b in Severe AADC Deficiency
Condition(s) studied
Aromatic L-amino Acid Decarboxylase Deficiency
Investigational drug(s) / intervention(s)
VGN-R09b injection
VGN-R09b injection: Two levels of VGN-R09b will be injected into bilateral putamen in dose-escalating phase, and one dose level will be injected in dose confirming phase
Study summary
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
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).
Primary outcome measure(s)
- Number of Adverse Events (AEs), Serious Adverse Events (SAEs) — up to Week 52
Vital signs, physical examination, laboratory test will be monitored after drug injection
- Number of subjects who achieved motor development milestones — up to 24 months
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.
Trial sites (1)
| Facility | City | Region | Status |
| Shanghai |
Shanghai |
Shanghai Municipality |
|
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