E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Deficiency in the AADC Gene enzyme |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This clinical trial is to prove the efficacy and safety of AAV2-hAADC to treat participants with AADC deficiency. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•With a confirmed diagnosis of AADC, including cerebrospinal fluid analysis to show reduced levels of neurotransmitter metabolites, HVA and 5-HIAA, and higher L-Dopa, together with more than one mutation within AADC gene. •Classical clinical characteristics of AADC deficiency, such as oculogyric crises, hypotonia, and developmental retardation. •The sick child has to be over 2 years old or a head circumference big enough for surgery. |
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E.4 | Principal exclusion criteria |
•Significant brain structure abnormality. •Participants with any health or neurological doubts that may increase the risk of surgery cannot join this trial. The Principal Investigator has the right to evaluate the feasibility of participants for this trial based on participant's health condition. •Since high-level neutralizing antibodies may disturb the therapeutic effect of gene therapy, participants with anti-AAV2 neutralizing antibody titer over 1,200 folds or an enzyme-linked immunosorbent assay (ELISA) optical density (OD) over 1 cannot be enrolled into this trial. •Participants cannot take any medications that may affect this clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Increase From Baseline in Neurotransmitter Metabolites (HVA or HIAA) detectable in the Cerebrospinal Fluid (CSF) •Change From Baseline, with an Improvement of at Least 10 Points, in the Peabody Developmental Motor Scales – 2nd Edition (PDMS II) Scores |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Month 3, Month 6, Month 9, and Month 12 |
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E.5.2 | Secondary end point(s) |
•Absence of Intracranial Bleeding Episodes That Require Surgical Management •Number of Craniotomy Induced CSF Exudation Episodes •Severity of Post-Surgery Hyperactivity (When Feeding is Affected, and then a Nasogastric Tube is Required) •Incidence of Other Severe Adverse Events •Weight Gain •Increased Signal Intensity of Dopamine in Putamen During Positron Emission Tomography (PET) Imaging •Increased Score in Other Development Evaluations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Month 3, Month 6, Month 9, and Month 12 Month 24 and Month 60 (for the endpoint reporting "Increased Signal Intensity of Dopamine in Putamen During PET Imaging")
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluate the efficacy and safety of AAV2-hAADC. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Feasibility study to evaluate efficacy and safety of AAV2-hAADC |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 60 |