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 expansion study is to offer participants, who are not enrolled into the Phase I/II trial, a chance of treatment to extend the experience in this gene therapy and to increase the dose slightly. |
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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, 5-HIAA, and higher levodopa (L-Dopa), or with more than 1 mutation within AADC gene. •Classical clinical characteristics of AADC deficiency, such as oculogyric crises, hypotonia, and developmental retardation. •The child participant has to be over 2 years old or a thickness of skull enough for surgery. •The child participant has to be under 6 years old (72 months) before being treated with study drugs. |
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E.4 | Principal exclusion criteria |
•Significant brain structure abnormality determined by the physician. •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. •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 recruited 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, 7 days after surgery, 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 Dyskinesia (if Feeding is Affected, and Then 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 •Increase Score in Other Development Evaluations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, 7 days after surgery, Month 3, Month 6, Month 9, Month 12, and Month 13 |
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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 |
This clinical trial expansion study is to offer participants, who are not enrolled into the Phase I/II trial, a chance of treatment to evaluate the safety and efficacy of AAV2-hAADC and to increase the dose slightly. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | Yes |
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 | 12 |