Clinical Trial Results:
A Phase 1/2 Clinical Trial for Treatment of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC (Eladocagene Exuparvovec)
|
Summary
|
|
EudraCT number |
2019-003032-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
18 Dec 2020
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
31 Aug 2022
|
First version publication date |
31 Aug 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
AADC-010
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01395641 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
National Taiwan University
|
||
Sponsor organisation address |
7 Chung Shan South Road, Taipei City, Taiwan, 10002
|
||
Public contact |
Wuh-Liang Hwu, National Taiwan University, 886 223123456 71938,
|
||
Scientific contact |
Wuh-Liang Hwu, National Taiwan University, 886 223123456 71938,
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-002435-PIP01-18 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
18 Dec 2020
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
18 Dec 2020
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Dec 2020
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objectives of this trial were to understand if the expression of human aromatic L-amino acid decarboxylase (hAADC) gene transferred by adeno-associated viral vector, serotype 2 (AAV2) vector may facilitate the conversion from L3,4-dihydroxyphenylalanine (L-DOPA) to dopamine to improve the motor function of participants; and to ensure the safety of hAADC gene transfer by AAV2 vector for children with AADC deficiency.
|
||
Protection of trial subjects |
This study was conducted in full accordance with the International Council for Harmonisation (ICH), Good Clinical Practice (GCP), Consolidated Guideline (E6), and any applicable national and local laws and regulations.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Aug 2014
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Taiwan: 10
|
||
Worldwide total number of subjects |
10
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
1
|
||
Children (2-11 years) |
9
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||
|
Recruitment
|
|||||||||||||
Recruitment details |
- | ||||||||||||
|
Pre-assignment
|
|||||||||||||
Screening details |
A total of 10 participants were enrolled and treated in the study. | ||||||||||||
|
Period 1
|
|||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
|
Arms
|
|||||||||||||
|
Arm title
|
Eladocagene Exuparvovec | ||||||||||||
Arm description |
Participants received eladocagene exuparvovec administered during a single operative session at a dose of 0.45×10^11 viral genomes (vg) and a volume of 80 microliters (μL) per site to 4 sites (2 per putamen), for a total dose of 1.8×10^11 vg and a total volume of 320 μL. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Eladocagene Exuparvovec
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
AAV2-hAADC
|
||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||
Routes of administration |
Intracerebral use
|
||||||||||||
Dosage and administration details |
Eladocagene exuparvovec gene therapy was administered in a single operative session using an established stereotactic neurosurgical procedure at a fixed dose.
|
||||||||||||
|
|||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Eladocagene Exuparvovec
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received eladocagene exuparvovec administered during a single operative session at a dose of 0.45×10^11 viral genomes (vg) and a volume of 80 microliters (μL) per site to 4 sites (2 per putamen), for a total dose of 1.8×10^11 vg and a total volume of 320 μL. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Eladocagene Exuparvovec
|
||
Reporting group description |
Participants received eladocagene exuparvovec administered during a single operative session at a dose of 0.45×10^11 viral genomes (vg) and a volume of 80 microliters (μL) per site to 4 sites (2 per putamen), for a total dose of 1.8×10^11 vg and a total volume of 320 μL. | ||
|
|||||||||
End point title |
Change From Baseline in Neurotransmitter Metabolite Homovanillic Acid (HVA) in Cerebrospinal Fluid at Month 12 [1] | ||||||||
End point description |
The presence of neurotransmitter metabolite HVA (the metabolite of dopamine) was measured in cerebrospinal fluid (CSF). Intent-to-treat (ITT) population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline, Month 12
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Proportion of Participants who Achieved an Increase of at least 10-Points From Baseline in Peabody Developmental Motor Scale, Second Edition (PDMS-2) Total Score at Month 12 [2] | ||||||||
End point description |
The PDMS-2 is a standardized, norm-referenced test, which includes gross motor and fine motor domains. All items of the PDMS-2 are scored on a 3-point scale (0 to 2): 0 is assigned when the child cannot perform the item or when the attempts do not meet the criteria of the item; 1 is assigned when the attempts do not meet for successful performance, but the behavior is emerging; and 2 indicates that the behavior is emerging, and the criterion for successful performance is fully met. The total score is the sum of all of the subscale scores (stationary, locomotion, object manipulation, grasping, visual-motor integration, and reflexes [the latter was not assessed in this population]) and varies based on age. The total score ranges from 0 to 482, where higher scores indicating more advanced motor function. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 12
|
||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in Neurotransmitter Metabolite 5-Hydroxyindoleacetic Acid (5-HIAA) in Cerebrospinal Fluid at Month 12 [3] | ||||||||
End point description |
The presence of neurotransmitter metabolite 5-HIAA (the metabolite of serotonin) was measured in CSF. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline, Month 12
|
||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants who Achieved the Key Motor Milestones at Month 60 [4] | ||||||||||||||||
End point description |
PDMS-2 motor skill items assess key motor milestones of 1) full head control (Stationary Item 10), 2) sitting unassisted (Stationary Item 14), 3) standing with support (Locomotion Item 28), and 4) walking with assistance (Locomotion Item 34), as these were the key motor milestones used to define the natural history of participants with AADC deficiency. Each skill item was assessed as a 3-level scoring system: 0 = skill is not met, 1 = skill is emerging and shows a clear resemblance to mastery, and 2 = child has mastered the motor skill. For each of the 4 key motor milestones, the numeric score of “2” was translated into mastery of the milestone, indicating that the child achieved the milestone; a score of “1” translated into demonstrating emerging skill, and was often indicative of eventually mastering the milestone; a numeric score of “0,” “or unscored” equated to “fail,” and therefore the participant did not achieve the milestone. ITT population included all enrolled participants.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Month 60
|
||||||||||||||||
| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||
End point title |
Number of Participants With Intracranial Bleeding That Required Surgical Treatment | ||||||
End point description |
Safety analysis set included all treated participants
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Baseline up to Month 60
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Number of Participants With Craniotomy-induced Cerebrospinal Fluid (CSF) Exudation (CSF Leaks) | ||||||
End point description |
Safety analysis set included all treated participants.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Baseline up to Month 60
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||
End point title |
Number of Participants With Adverse Events (AEs) Potentially Associated With Post-surgical Hyperactivity | ||||||||||||||
End point description |
AEs potentially associated with post-surgical hyperactivity included dyskinesia, diarrhoea, initial insomnia, and salivary hypersecretion. Safety analysis set included all treated participants
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline up to Month 60
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||
End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | ||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are those AEs with an onset on or after the surgery start time; AEs with a missing onset date were considered treatment emergent. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. Safety analysis set included all treated participants.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Baseline up to Month 60
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Change From Baseline in Body Weight at Month 12 | ||||||||
End point description |
ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Month 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in Putaminal Positron Emission Tomography (PET)-Specific Uptake at Month 60 | ||||||||
End point description |
Expression and activity of the AADC enzyme in the putamen was assessed by PET imaging using L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA), a positron-emitting fluorine-labeled version of levodopa, which is a substrate for AADC. The 18F-DOPA is administered intravenously, crosses the blood-brain barrier, and is taken up by the presynaptic nigrostriatal dopaminergic neurons in the putamen and converted by AADC to dopamine. Therefore, increased 18F-DOPA putamen uptake over time objectively demonstrates newly produced dopamine and the presence of functional AADC enzyme. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Month 60
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in PDMS-2 Total Score at Month 60 | ||||||||
End point description |
The PDMS-2 is a standardized, norm-referenced test, which includes gross motor and fine motor domains. All items of the PDMS-2 are scored on a 3-point scale (0 to 2): 0 is assigned when the child cannot perform the item or when the attempts do not meet the criteria of the item; 1 is assigned when the attempts do not meet for successful performance, but the behavior is emerging; and 2 indicates that the behavior is emerging, and the criterion for successful performance is fully met. The total score is the sum of all of the subscale scores (stationary, locomotion, object manipulation, grasping, visual-motor integration, and reflexes [the latter was not assessed in this population]) and varies based on age. The total score ranges from 0 to 482, where higher scores indicating more advanced motor function. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Month 60
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in Alberta Infant Motor Scale (AIMS) Total Score at Month 60 | ||||||||
End point description |
The AIMS is a validated, 58-item observational measure that assesses the sequential development of motor milestones. Each item is scored as “observed” or “not observed,” and a point is given for each observed item. The AIMS total score is calculated by summing the scores for the 58 items, with a range of scores from 0 to 58. Higher scores indicate more advanced motor function. Each of the 58 items consists of an artist’s drawing and a photograph of a young child performing a particular movement. The AIMS scale requires minimal handling of the child and assesses the child’s movement in 4 positions: prone, supine, sitting, and standing. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Month 60
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline in Bayley Scale of Infant and Toddler Development, Third Edition [Bayley-III]) Total Score at Month 60 | ||||||||
End point description |
The Bayley-III has 5 main subscales: Cognitive Scale, Language Scale (expressive and receptive), Motor Scale, Social Emotional Scale, and Adaptive Behavior Scale. The Cognitive Scale includes items such as attention to familiar and unfamiliar objects, looking for a fallen object, and pretend play. The Language Scale includes understanding and expression of language, for example, recognition of objects and people, following directions, and naming objects and pictures. The study only used the cognitive scales and language scales for evaluation, and Bayley-III “total” score (refers to the sum of the Cognition, Expressive Communication, and Receptive Communication subscales) ranges from 40 to 160, where higher score indicated stronger skills and abilities and lower scores indicate possible delay/deficit. ITT population included all enrolled participants. Here, overall number of participants analyzed = participants evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Month 60
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to Month 60
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety analysis set included all treated participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Eladocagene Exuparvovec
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received eladocagene exuparvovec administered during a single operative session at a dose of 0.45×10^11 viral genomes (vg) and a volume of 80 microliters (μL) per site to 4 sites (2 per putamen), for a total dose of 1.8×10^11 vg and a total volume of 320 μL. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
30 Nov 2014 |
• Updated background information for AADC deficiency in Taiwan;
• Updated treatment information for AADC deficiency with citation of recent articles;
• Expanded the description of the mechanism of action of PD;
• Added preclinical study results;
• Added description of infusion of AADC vector;
• Specified the number of post-study visits and associated procedures;
• Removed details of by-visit procedures as they are present in the summary of items and schedules of treatment and examinations;
• Added a subsection describing dosage and infusion of viral vector;
• Added a subsection on allowable concomitant medications;
• Added a new section describing the expected duration of the study;
• Added a new section header for classifying the radiologic and functional assessments to be used for postsurgical evaluation;
• Added subsection on treatment and examination procedures to be performed at each stage of the study;
• New section added to provide timing of standardized rehabilitation therapy;
• Modified the endpoints to evaluate neurotransmitter metabolites and assess PDMS-2 score;
• Modified the secondary endpoints to add evaluation of craniotomy-induced CSF exudation and effect on feeding and need for nasogastric tube as well as adding collection of severity information for adverse events;
• New section added to describe the preparation of AAV2-hAADC viral vector and genome titers;
• Included a summary of AAV2-hAADC toxicity in rats;
• New section added to hypothesize the anticipated outcomes of the study;
• New section header added along with introductory paragraph describing the collection of information on AEs, TEAEs, and SAEs;
• Added description for management of severe symptoms;
• Added description on risks of study evaluation, including respiratory risk, use of anesthesia, and lumbar puncture;
• Added statements summarizing the damage and insurance compensation and withdrawal from the study; |
||
23 May 2019 |
Updated information on subinvestigators. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
