An Open-Label Trial to Address the Safety of the SmartFlow MR-Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Subjects
Phase: PHASE2
Conditions: AADC Deficiency
Sponsor: PTC Therapeutics

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CLINICAL PROTOCOL 
AN OPEN-LABEL TRIAL TO ADDRESS THE SAFETY OF THE 
SMARTFLOW MR-COMPATIBLE VENTRICULAR CANNULA FOR 
ADMINISTERING ELADOCAGENE EXUPARVOVEC TO PEDIATRIC 
SUBJECTS 
PTC-AADC-GT-002 
01 SEPTEMBER 2023 
VERSION 11.0 
PTC THERAPEUTICS GT, INC. 
100 CORPORATE COURT 
SOUTH PLAINFIELD, NJ 07080 USA 
Notice of Proprietary Information: This document contains confidential information owned by or in the 
possession/control of PTC Therapeutics GT, Inc. Except as may otherwise be permitted in writing, by accepting or 
reviewing these materials, you agree that this information should not be disclosed to others (except where required by 
applicable law) and should not be used for unauthorized purposes. In the event of an actual or suspected breach of this 
obligation, PTC Therapeutics GT, Inc. should be notified promptly.
NCT #: NCT04903288

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PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PTC Therapeutics, Inc. 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
PTC Therapeutics, Inc. 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
PTC Therapeutics, Inc. 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The eSignature page is located on the last page. 

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PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE 
 
I have read the protocol document and, on behalf of my institution, agree to comply with the 
protocol and all applicable regulations. 
 
 
 
 
Principal Investigator 
 
Date 
 
 
 
Institution: 
 
Address: 
 
City: 
 
State/Province:  
Country: 
 
Phone: 
 
Fax: 
 
E-mail: 
 

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SYNOPSIS 
Name of 
Sponsor/Company: 
PTC THERAPEUTICS, INC. 
Study Number: 
PTC-AADC-GT-002 
Study Title: 
An Open-Label Trial to Address the Safety of the SmartFlow 
MR-Compatible Ventricular Cannula for Administering Eladocagene 
Exuparvovec to Pediatric Subjects 
Study Objectives: 
Primary Study Objectives 
• To assess the pharmacodynamics (PD) of eladocagene 
exuparvovec treatment by evaluation of homovanillic acid 
(HVA) levels at 8 weeks after administration 
• To assess the safety of the SmartFlow magnetic resonance 
(MR)-compatible ventricular cannula for administering 
eladocagene exuparvovec to pediatric subjects 
Secondary Study Objectives 
The secondary study objectives of the study are as follows: 
• To assess the PD of eladocagene exuparvovec by evaluation of 
the following: 
o HVA at Week 48 
o Positron emission tomography (PET) at Weeks 8 and 48 
o 5-hydroxyindoleacetic acid [5-HIAA] at Weeks 8 and 48 
o 3-O-methyldopa [3-OMD]) at Weeks 8 and 48 
• To evaluate the long-term efficacy of eladocagene exuparvovec 
through Month 60 as assessed by the following: 
o Motor milestone attainment 
o Peabody Developmental Motor Scale, second edition 
(PDMS-2) score 
o Bayley Scale of Infant Development, third edition 
(Bayley-III) 
o EQ-5D-Y 
o Body weight 
o Aromatic L-amino acid decarboxylase (AADC)-specific 
symptoms 
• To evaluate the safety of eladocagene exuparvovec treatment as 
assessed by treatment-emergent adverse events (TEAEs), 
neurological examinations, magnetic resonance imaging (MRI), 
and clinical laboratory tests.  
Phase of Trial: 
Phase 2  
Study Design: 
This is an open-label study in subjects with AADC. Eligible pediatric 
subjects will receive eladocagene exuparvovec at 1.8×1011 vector 
genomes (vg) via the SmartFlow MR--compatible ventricular cannula 
in a single operative session. Subjects will receive standard of care for 
AADC deficiency during the study. This study will have a Trial Phase, 
an Extension Phase, and a Long-Term Extension Phase. The primary 
objectives of the Trial Phase are to assess the PD of eladocagene 

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exuparvovec treatment by evaluation of HVA levels and to assess the 
safety of the SmartFlow MR-compatible- ventricular cannula for 
administering eladocagene exuparvovec to pediatric subjects with 
AADC deficiency. The secondary objectives of the Trial Phase are to 
further assess the PD of eladocagene exuparvovec in subjects with 
AADC deficiency using neurotransmitter metabolite assessment and 
PET analysis. The Extension Phase is designed to capture additional 
clinical information for eladocagene exuparvovec through study 
evaluations, changes in motor development, AADC-specific symptoms, 
and other PD measures. The Extension Phase will be complete at 
48 weeks after administration of eladocagene exuparvovec. The 
Long-Term Extension Phase will capture long-term safety and efficacy 
data, for subjects treated with eladocagene exuparvovec, through 
Month 60. 
A Data Safety Monitoring Board (DSMB) will conduct a review of 
safety data as outlined in the DSMB charter. Review by DSMB will not 
be required in order to enroll successive subjects. The DSMB will 
monitor ongoing study results to ensure subject well-being, safety, and 
study integrity.  
Study Population: 
Pediatric subjects with AADC deficiency. At minimum, 3 subjects will 
be enrolled for this study. 
Inclusion/ 
Exclusion Criteria: 
Inclusion criteria: 
1. Pediatric subjects must have genetically confirmed AADC 
deficiency with typical clinical characteristics and decreased 
AADC enzyme activity in plasma. 
2. Age range from 1 year to <18 years. 
3. Cranium sufficiently developed to allow placement of 
ClearPoint system for stereotactic surgery. 
4. Persistent neurological defects secondary to AADC deficiency 
despite standard medical therapy (dopamine agonists, 
monoamine oxidase inhibitor, pyridoxine, or other forms of 
vitamin B6) in the opinion of the investigator. 
5. Unable to ambulate independently (with or without assistive 
device). 
6. Baseline hematology, chemistry, and coagulation values within 
the normal pediatric laboratory value ranges, unless in the 
investigator's opinion the out-of-range values are not clinically 
significant with respect to the subject’s suitability for surgery. 
7. Subject must test negative for coronavirus disease of 2019 
(COVID-19) a maximum of 72 hours prior to receiving gene 
therapy. 
8. Subject must be on stable dosage for 3 months prior to baseline 
for all medications related to treatment of AADC deficiency, 
including dopamine agonists, monoamine oxidase inhibitors, 
anticholinergic drugs, and vitamin B6. 

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9. Females of childbearing potential must have a negative 
pregnancy test at screening and baseline and agree to abstinence 
or double-barrier form of contraception for the duration of the 
study following discharge from the hospital (acceptable 
methods will be determined by the site). 
10. Males sexually active with females of childbearing potential 
must agree to use a barrier method of birth control during the 
study following discharge from the hospital. 
11. Parent(s)/legal guardian(s) with custody of the subject must 
agree to comply with the requirements of the study, including 
the need for frequent and prolonged follow-up. 
12. Parent(s)/legal guardian(s) with custody of the subject must give 
their consent for subject to enroll in the study. 
Exclusion criteria: 
1. The subject has presence of other significant medical or 
neurological conditions that would create an unacceptable 
operative or anesthetic risk. 
2. Subjects with pyridoxine 5'-phosphate oxidase or 
tetrahydrobiopterin (BH4) deficiency. 
3. Contraindication for imaging studies (computed tomography 
[CT] scan, PET, or MRI), including sedation limitations or 
metal that would interfere with a brain MRI. 
4. Anti-adeno-associated virus, serotype 2 (anti-AAV2) antibody 
titer higher than 1:1200 or >1 optical density value by 
enzyme-linked immunosorbent assay. 
5. Subjects that have received treatment with other experimental 
therapies within the last 24 weeks prior to planned gene therapy 
administration, or any treatment ever with a gene therapy. 
6. Evidence of a clinically active infection. 
7. Females who are pregnant or breast feeding. 
Study Treatment: 
Eladocagene exuparvovec, administered 1.8×1011 vg during a one-time 
surgical procedure. 
Study Endpoints 
and Evaluations: 
Primary Endpoints and Evaluations 
• The primary efficacy endpoint is the change from baseline in 
HVA metabolite levels at the end of the Trial Phase (8 weeks 
after administration). 
• The primary safety endpoint is the assessment of adverse events 
(AEs) associated with the surgical administration of 
eladocagene exuparvovec to pediatric subjects using the 
SmartFlow MR-compatible ventricular cannula at the end of 
Trial Phase (8 weeks after administration). 

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Secondary 
Endpoints 
The secondary endpoints are as follows: 
• Change from baseline in neurotransmitter cerebrospinal fluid 
(CSF) metabolite HVA (at 48 weeks after administration) 
• Change from baseline in PET imaging of putaminal-specific 
L-6-[18F] fluoro-3,4-dihydroxyphenylalanine (18F-DOPA) PET 
uptake at the end of the Trial Phase (8 weeks after 
administration) and the Extension Phase (48 weeks after 
administration) 
• Change from baseline in neurotransmitter CSF metabolites 
5-HIAA and 3-OMD at 8 and 48 weeks after administration 
• Attainment of motor milestones 
• Motor development as assessed by the PDMS-2 
• Cognitive and language development as assessed by Bayley-III 
• Change in EQ-5D-Y 
• Change in body weight 
• Assessment of AADC-specific symptoms 
• Overall safety profile characterized by type, frequency, severity, 
timing, and relationship to study treatment of any TEAEs, 
neurological examination findings, brain imaging, or laboratory 
abnormalities. 
Statistical 
Methods: 
Summaries and descriptive statistics will be provided for PD, safety, 
and efficacy variables from time of gene therapy administration until 
the end of follow-up. If needed, summaries will be provided for PD, 
efficacy, and safety variables at a timepoint that matches the agreement 
with the health authority. 
Observed values and change from baseline in HVA at Week 8 will be 
summarized using descriptive statistics (count, mean, standard 
deviation, median, minimum, and maximum) for each timepoint 
Observed values and change from baseline in the neurotransmitter CSF 
metabolites HVA, 5-HIAA, 3-OMD in CSF; brain 18F-DOPA PET; 
PDMS-2 total and subscale scores; Bayley-III cognitive and total 
language subscale scores; EQ-5D-Y scores; body weight; and AADC-
specific symptoms will be summarized using descriptive statistics 
(count, mean, standard deviation, median, minimum, and maximum) or 
proportion as appropriate for each timepoint. 
The number and percentage of subjects who achieve each motor 
milestone will be summarized by timepoint. 
Oculogyric crisis diary data will be summarized by severity, frequency, 
and proportion and duration of time subjects experienced oculogyric 
crises (OGC) during the study for selected timepoints, as appropriate. 
Respiratory infection rate will be summarized over time. 
The primary safety analysis will focus on TEAEs that are defined as 
AEs with a start date after or worsen after receiving eladocagene 
exuparvovec. 
The time of gene therapy administration will be the start time of the 
first infusion. All AEs reported will be coded using MedDRA. The 

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number and proportion of subjects reporting TEAE will be summarized 
by System Organ Class (SOC) and by Preferred Term (PT) within 
SOC. Summaries will also be provided for each severity grade, 
relationship to the cannula device, to gene therapy, and to neurosurgical 
procedure, and for AEs of special interest. 
The number of subjects who experience dyskinesia, number of 
dyskinesia episodes, median time to first episode, and summary 
statistics for duration of dyskinesia events will be provided. 
Physical examination, vital signs, MRI, clinical laboratory values, T-
cell, anti-AAV2 antibody values, and viral shedding will be 
summarized by visit, and shift table(s) will be provided if appropriate. 

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PROTOCOL IDENTIFIERS AND STUDY PERSONNEL 
Project Code 
PTC-AADC 
Therapeutic Area 
Gene therapy 
PTC Therapeutics Substance Identifier 
Eladocagene exuparvovec 
IND Number 
IND 019653 
EudraCT Number 
N/A 
ClinicalTrials.gov Identifier 
NCT04903288 
Protocol Number 
PTC-AADC-GT-002 
Protocol Version 
Version 11.0 
Protocol Version Date 
01 September 2023 
Protocol Phase 
Phase 2 
Protocol Title 
An Open-Label Trial to Address the Safety of the 
SmartFlow MR-Compatible Ventricular Cannula for 
Administering Eladocagene Exuparvovec to Pediatric 
Subjects 
PTC Medical Monitor 
 
PTC Biostatistician 
 
PTC Study Manager 
 

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TABLE OF CONTENTS 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES..............................................2 
PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE............................................3 
SYNOPSIS  ......................................................................................................................................4 
PROTOCOL IDENTIFIERS AND STUDY PERSONNEL ...........................................................9 
TABLE OF CONTENTS ...............................................................................................................10 
LIST OF TABLES .........................................................................................................................13 
LIST OF FIGURES .......................................................................................................................13 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................14 
1. 
INTRODUCTION ......................................................................................................16 
1.1. 
Background Information .............................................................................................16 
1.1.1. 
Aromatic L-amino Acid Decarboxylase Deficiency ..................................................16 
1.2. 
Stage of Development .................................................................................................17 
1.3. 
Trial Rationale ............................................................................................................18 
1.4. 
Risk-Benefit Assessment ............................................................................................19 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................20 
2.1. 
Primary Objectives .....................................................................................................20 
2.2. 
Secondary Objectives .................................................................................................20 
2.3. 
Primary Endpoints ......................................................................................................20 
2.4. 
Secondary Endpoints ..................................................................................................21 
3. 
STUDY DESCRIPTION ............................................................................................22 
3.1. 
Study Design ...............................................................................................................22 
3.2. 
Justification of Dose ...................................................................................................22 
3.3. 
End of Study Definition ..............................................................................................23 
4. 
STUDY POPULATION .............................................................................................24 
4.1. 
Inclusion Criteria ........................................................................................................24 
4.2. 
Exclusion Criteria .......................................................................................................25 
4.3. 
Screen Failures ............................................................................................................25 
5. 
STUDY INTERVENTION ........................................................................................26 
5.1. 
Study Intervention Description ...................................................................................26 
5.2. 
Dosing and Administration .........................................................................................26 
5.3. 
Preparation/Handling/Storage/Accountability ............................................................26 
5.3.1. 
Preparation and Handling ...........................................................................................26 

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5.3.2. 
Storage ........................................................................................................................27 
5.3.3. 
Accountability .............................................................................................................27 
5.3.4. 
Formulation, Appearance, Packaging, and Labeling ..................................................27 
5.4. 
Concomitant Therapy .................................................................................................27 
5.5. 
Organ Donation ..........................................................................................................28 
6. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ..................................................................29 
6.1. 
Stopping Rules ............................................................................................................29 
6.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................29 
6.3. 
Lost to Follow-Up.......................................................................................................30 
7. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................31 
7.1. 
Schedule of Events and Study Parameters ..................................................................31 
7.2. 
Primary Endpoints ......................................................................................................37 
7.2.1. 
HVA Levels ................................................................................................................37 
7.2.2. 
Safety of Surgical Administration Using the SmartFlow Cannula .............................37 
7.3. 
Secondary Endpoints ..................................................................................................37 
7.3.1. 
18F-DOPA Positron Emission Tomography ...............................................................37 
7.3.2. 
Peabody Developmental Motor Scale, Second Edition ..............................................38 
7.3.3. 
Bayley Scale of Infant Development, Third Edition ..................................................39 
7.3.4. 
EQ-5D-Y .....................................................................................................................40 
7.3.5. 
Body Weight ...............................................................................................................40 
7.3.6. 
AADC-Specific Symptoms ........................................................................................40 
7.3.7. 
Measurement of 3-OMD and 5-HIAA .......................................................................41 
7.4. 
Home Care Services ...................................................................................................41 
7.5. 
Safety Assessments .....................................................................................................41 
7.5.1. 
Peri-Operative Safety Monitoring ..............................................................................41 
7.5.2. 
Adverse Events and Serious Adverse Events .............................................................42 
7.5.2.1. 
Definition of Adverse Events .....................................................................................42 
7.5.2.2. 
Definition of Serious Adverse Events ........................................................................43 
7.5.3. 
Adverse Events of Special Interest .............................................................................44 
7.5.3.1. 
Risks of Neurosurgical Procedure ..............................................................................44 
7.5.3.2. 
Dyskinesia ...................................................................................................................44 
7.5.3.3. 
Cerebrospinal Fluid Leaks ..........................................................................................44 

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7.5.4. 
Adverse Event Recording ...........................................................................................44 
7.5.5. 
Describing Adverse Event Relationship to Gene Therapy or Surgery .......................45 
7.5.6. 
Grading of Severity of Adverse Events ......................................................................46 
7.5.7. 
Follow-Up of Unresolved Adverse Events .................................................................46 
7.5.8. 
Adverse Event Reporting Period ................................................................................46 
7.5.9. 
Serious Adverse Event Reporting ...............................................................................47 
7.5.10. 
PTC Adverse Event Reporting Requirement ..............................................................47 
7.5.11. 
Other Safety Assessments ...........................................................................................48 
7.5.12. 
Safety Assessment Committee ...................................................................................48 
8. 
STATISTICAL METHODS AND DATA ANALYSIS ............................................49 
8.1. 
Sample Size Determination ........................................................................................49 
8.2. 
Subject Population(s) for Analysis .............................................................................49 
8.3. 
General Approach .......................................................................................................49 
8.3.1. 
Subject Disposition and Characteristics .....................................................................49 
8.3.2. 
Analysis of Primary Endpoints ...................................................................................49 
8.3.2.1. 
Primary Efficacy Analysis ..........................................................................................49 
8.3.2.2. 
Primary Safety Analysis .............................................................................................50 
8.3.3. 
Analysis of Secondary Endpoints ...............................................................................50 
8.3.4. 
Planned Interim Analysis ............................................................................................50 
9. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................51 
9.1. 
Regulatory, Ethical, and Study Oversight Considerations .........................................51 
9.1.1. 
Informed Consent Process ..........................................................................................51 
9.1.2. 
Study Discontinuation and Closure ............................................................................51 
9.1.3. 
Confidentiality and Privacy ........................................................................................51 
9.1.4. 
Future Use of Stored Specimens and Data .................................................................52 
9.1.5. 
Safety Oversight .........................................................................................................53 
9.1.6. 
Clinical Monitoring ....................................................................................................53 
9.1.7. 
Quality Assurance and Quality Control ......................................................................54 
9.1.8. 
Data Handling and Record Keeping ...........................................................................54 
9.1.9. 
Protocol Deviations ....................................................................................................54 
9.1.10. 
Publication and Data Sharing Policy ..........................................................................55 
9.1.11. 
Additional Considerations ..........................................................................................56 

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10. 
PROTOCOL AMENDMENT HISTORY ..................................................................57 
10.1. 
Version 1.1: 24 March 2020 .......................................................................................57 
10.2. 
Version 2.0: 17 July 2020 ...........................................................................................58 
10.3. 
Version 3.0: 17 August 2020 ......................................................................................60 
10.4. 
Version 4.0: 24 November 2020 .................................................................................61 
10.5. 
Version 5.0: 21 April 2021 .........................................................................................61 
10.6. 
Version 6.0: 16 August 2021 ......................................................................................63 
10.7. 
Version 7.0: 11 November 2021 .................................................................................65 
10.8. 
Version 8.0: 22 March 2022 .......................................................................................66 
10.9. 
Version 9.0: 20 July 2022 ...........................................................................................67 
10.10. 
Version 10.0: 28 April 2023 .......................................................................................67 
10.11. 
Version 11.0: 01 September 2023 ..............................................................................68 
11. 
REFERENCES ...........................................................................................................69 
APPENDIX 1. PDMS-2 SCORE SHEET...................................................................................71 
 
LIST OF TABLES 
Table 1: 
Schedule of Events for Trial Phase .............................................................................31 
Table 2: 
Schedule of Events for Extension Phase ....................................................................34 
Table 3: 
Schedule of Events for Long-Term Extension Phase .................................................36 
Table 4: 
Relationship of Gene Therapy to Adverse Event .......................................................45 
Table 5: 
Grading of Adverse Event Severity Grade .................................................................46 
Table 6: 
Investigator Site Requirements for Reporting Adverse Events ..................................46 
 
LIST OF FIGURES 
Figure 1: 
Diagram of Eladocagene Exuparvovec Expression Cassette .....................................26 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or 
Specialized Term 
Explanation 
18F-DOPA 
L-6-[18F] fluoro-3,4-dihydroxyphenylalanine 
3-OMD 
3-O-methyldopa 
5-HIAA 
5-hydroxyindoleacetic acid 
5-HTP 
5-hydroxytryptophan 
AADC 
Aromatic L-amino acid decarboxylase  
AADC 
Aromatic L-amino acid decarboxylase (gene) 
AAV2 
Adeno-associated virus, serotype 2 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AIMS 
Alberta Infant Motor Scale  
aPTT 
Activated partial thromboplastin time 
Bayley-III 
Bayley Scale of Infant Development, third edition 
BH4 
Tetrahydrobiopterin 
BL  
Baseline 
CBC 
Complete blood count 
cDNA 
Complementary deoxyribonucleic acid 
CMP 
Comprehensive metabolic panel 
CMV IEP 
Cytomegalovirus immediate-early promoter 
COVID-19 
Coronavirus disease of 2019 
CRO 
Contract Research Organization 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
D 
Day 
DDC 
DOPA decarboxylase (gene) 
diff 
Differential count 
Disc 
Discharge 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eDiary 
Electronic diary 
ET 
Early termination 
GCP 
Good Clinical Practice 
hAADC 
Human aromatic L-amino acid decarboxylase 
HBG2/3 
Human β globin partial intron 2/partial exon 3 
HVA 
Homovanillic acid 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICU 
Intensive care unit 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
ITR 
Inverted terminal repeat 
L-DOPA 
L-3,4-dihydroxyphenylalanine 
MBq 
Megabecquerel 
mCi 
Millicurie 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHPG 
3-methoxy-4-hydroxyphenylglycol 
MR 
Magnetic resonance 

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Abbreviation or 
Specialized Term 
Explanation 
MRI 
Magnetic resonance imaging 
OGC 
Oculogyric crisis/crises 
PD 
Pharmacodynamics 
PDMS-2 
Peabody Developmental Motor Scale, second edition 
PET 
Positron emission tomography 
PI 
Principal investigator  
Poly A 
Polyadenylation sequence 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
rAAV2 
Recombinant adeno-associated virus, serotype 2 
RBC 
Red blood cell (count) 
SAE 
Serious adverse event 
SOC 
System Organ Class 
SUV 
Standardized uptake value 
SUVmax 
Maximal standardized uptake value 
T1-MPRAGE  
T1-weighted magnetization prepared rapid gradient echo 
T2-FLAIR 
T2-weighted fluid-attenuated inversion recovery 
TEAE 
Treatment-emergent adverse event 
vg 
Vector genomes 
W 
Week 
WBC 
White blood cell (count) 

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1. 
INTRODUCTION 
This study will be 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 (eg, Code of Federal Regulations Title 21, Parts 50, 54, 56, 312, 
and 314; European Union Directive 2001/20/EC on the approximation of the laws, regulations, 
and administrative provisions of the Member States relating to the implementation of GCP in the 
conduct of clinical studies of medicinal products for human use). Standard medical care 
(prophylactic, diagnostic, and therapeutic procedures) will be the responsibility of the treating 
physician of the subject during the course of the study. 
1.1. 
Background Information 
1.1.1. 
Aromatic L-amino Acid Decarboxylase Deficiency 
Aromatic L-amino acid decarboxylase (AADC) deficiency is a monogenetic disorder of 
neurotransmitter synthesis that manifests in young children and most commonly results in 
complete arrest of motor development. AADC deficiency is a rare, autosomal recessive 
metabolic disorder resulting from mutations in the DOPA decarboxylase (DDC) gene that 
encodes for AADC. The DDC gene is located on chromosome 7p12.1-7p12.3 and contains 
15 exons. The AADC enzyme, which has 480 amino acids, is highly conserved across species 
and is expressed in the brain, sympathetic ganglia, and adrenal medulla. A total of 82 DDC 
variants have been identified and cataloged. Of these, 79 variants are known to lead to AADC 
deficiency (Wassenberg 2017). 
Patients with AADC deficiency have a wide range of clinical presentation. Patients may have 
some symptoms at birth, develop others a few weeks or months later, and symptoms in some 
cases may fluctuate in intensity and frequency (Brautigam 2000, Helman 2014). Of the limited 
reported cases of AADC deficiency, all patients had symptoms within the first year of life 
(mean age of 2.7 months) (Brun 2010, Wassenberg 2017). The mean age of diagnosis was about 
3.5 years, indicating the difficulties in recognizing the disease and subsequent delays in 
diagnosis (Brun 2010, Wassenberg 2017). 
The AADC enzyme deficiency results in a marked or complete loss of dopamine and serotonin 
production in the brain from birth. Consequently, AADC-deficient patients exhibit symptoms 
related to loss in dopamine signaling, affecting voluntary movements, cognitive functions, and 
emotion. Patients with AADC deficiency have arrested motor development despite essentially 
preserved neurophysiology and neuroanatomy as determined by brain imaging. These patients 
fail to achieve motor milestones typical of healthy children, such as full head control and ability 
to sit, stand, or walk. Patients also experience intellectual disability and show irritability, and are 
at risk of early death in the first decade of life (Korenke 1997, Pons 2004, Helman 2014). 
Eladocagene exuparvovec (AGIL-AADC) is a recombinant adeno-associated virus, serotype 2 
(rAAV2)-based gene therapy containing human AADC (hAADC) complementary 
deoxyribonucleic acid (cDNA). The rAAV2 vector delivers cDNA encoding a normal copy of 
the hAADC enzyme. This results in the production of functional AADC enzyme and completion 
of the biosynthesis of dopamine, enabling development of motor functions in patients with 
AADC deficiency. All patients with AADC deficiency can benefit from this gene therapy that 
targets the underlying cause of the disease (ie, mutation in the DDC gene that leads to AADC 
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Currently, eladocagene exuparvovec (Upstaza) is approved in the European Union and the 
United Kingdom. No other drug or gene therapy is approved for the treatment of AADC 
deficiency. Drug therapies presently prescribed for AADC deficiency are primarily intended to 
treat symptoms, and do not treat the underlying cause of the disease. Available pharmacological 
interventions include dopamine agonists, monoamine oxidase inhibitors, and pyridoxine 
therapies (Himmelreich 2019). Most patients, particularly those with no motor development, do 
not respond to available treatments because these therapies cannot replace or increase dopamine 
production in the brain to adequately improve motor function and allow achievement of 
developmental milestones (Brun 2010). AADC deficiency typically results in death in the first 
decade of life (National Center for Advancing Translational Sciences 2018). The lack of 
effective treatment clearly indicates that AADC deficiency is a high unmet medical need, and 
that therapies to treat AADC deficiency are urgently needed to provide lasting and clinically 
meaningful improvement in motor development and function. 
1.2. 
Stage of Development 
The eladocagene exuparvovec clinical program to date consists of 3 completed clinical studies 
and 1 ongoing long-term follow-up study in subjects with AADC deficiency. All studies are 
single-arm trials in which subjects received treatment with eladocagene exuparvovec. The first 
3 studies were conducted at the same center in Taiwan, the National Taiwan University Hospital. 
The efficacy findings across the studies were similar indicating the reproducibility of the 
following results: 
• Study AADC-CU/1601 (N=8) is completed and was a Phase 1 observational study 
that summarized data from an interventional, compassionate use program of subjects 
with AADC deficiency followed for 60 months (5 years). Evidence of a favorable 
safety profile and durable clinical benefit observed in the follow-up period of 
Study AADC-CU/1601 justified continued clinical development of eladocagene 
exuparvovec for treatment of AADC deficiency. 
• Study AADC-010 (N=10) is a completed, Phase 1/2, prospective, 60-month study; all 
subjects have been treated, with an average follow-up of 60 months (range 
12 to 62 months). 
• Study AADC-011 (N=12) is a completed Phase 2b, prospective, 13-month study. All 
subjects have been with an average follow-up of 12.5 months. 
Additionally, Study AADC-1602 is an ongoing long-term follow-up of subjects who were 
treated with eladocagene exuparvovec in Studies AADC-CU/1601, AADC-010, and AADC-011. 
As of 16 June 2023, data for 26 subjects are available in this study and the mean duration of 
follow-up is 78.8 months (range 27.2 to 126.5 months). 
The results of these clinical studies indicate that a single 1.8×1011 vector genomes (vg) or 
2.4×1011 vg dose of eladocagene exuparvovec administered through bilateral putaminal infusion 
results in rapid, clinically meaningful, and durable improvements in motor function and 
achievement of motor milestones that would otherwise not be achieved, as evidenced by the 
natural history cohort (Wassenberg 2017). Significant improvement from baseline in both gross 
and fine motor skills, as assessed by Peabody Developmental Motor Scale, second edition 
(PDMS-2) and Alberta Infant Motor Scale (AIMS) scores, were observed across the studies. The 

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dosing regimen also resulted in improvement in cognitive function and a reduction in neurologic 
events, such as floppiness (hypotonia) and dystonia. 
1.3. 
Trial Rationale 
The primary aims of this study are to demonstrate a post-therapy increase in homovanillic acid 
(HVA) and to establish the safety of the SmartFlow magnetic resonance (MR)-compatible 
ventricular cannula in the administration of eladocagene exuparvovec to subjects with AADC 
deficiency. 
HVA is a main metabolite of dopamine and HVA cerebrospinal fluid (CSF) levels are 
recognized as a proxy for dopamine levels in the brain. Given that dopamine depletion is the key 
element of the pathology of AADC deficiency, restoration of dopamine is the direct result of the 
gene therapy and is necessary for clinical benefit. The ability of HVA to reflect aberrant 
dopamine levels in the striatum in patients with AADC deficiency is supported by the fact that 
the treatment guidelines for AADC deficiency uses CSF HVA levels as one of the diagnostic 
criteria for the disease (Wassenberg 2017). 
Results from the previous 3 eladocagene exuparvovec studies support the use of change from 
baseline in CSF HVA levels as likely to predict clinical benefit. The results show the following: 
• Low levels of HVA at baseline are consistent with low dopamine levels on positron 
emission tomography (PET) imaging and with profound dopamine-related motor 
defects. 
• Following treatment, there was a statistically significant increase in CSF HVA levels 
that corresponded to de novo dopamine production—a direct result of the gene 
therapy. 
• A strong correlation existed between change from baseline in post-treatment CSF 
HVA levels and long-term clinical benefit. 
The safety and efficacy of eladocagene exuparvovec delivered by direct injection into the 
bilateral putamen via established stereotactic procedures using commercially available guidance 
systems has already been established in 3 clinical studies (Studies AADC-CU/1601, AADC-010, 
and AADC-011). The results from all 3 clinical studies showed that subjects treated with 
eladocagene exuparvovec initiated motor development that would otherwise not have likely 
developed. The cannula used in these prior studies to deliver gene therapy was manufactured by 
Eicom in Japan and is not available for commercial use in the United States. Therefore, this 
open-label study is being conducted with the MR-compatible ventricular cannula, which is 
available for commercial use in the United States, to establish safety of its use in administration 
of eladocagene exuparvovec to the putamen of pediatric subjects. 
The SmartFlow MR-compatible ventricular cannula has been used to administer eladocagene 
exuparvovec in the European Union both commercially and via early access programs and was 
also used previously to administer a similar viral vector to the putamen of adult subjects to treat 
Parkinson’s disease (Bankiewicz 2016, Christine 2019). The device will allow precise targeting 
of the putamen using stereotactic positioning of the cannula through the use of intraoperative 
magnetic resonance imaging (MRI). Because AADC deficiency is a rare disorder and because 
the method of administering treatment requires a neurosurgical procedure, a control group in 
which subjects are administered placebo or undergo a sham procedure will not be used. 

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1.4. 
Risk-Benefit Assessment 
AADC deficiency is a debilitating disease that results in near or complete arrest of motor 
development. AADC is an enzyme responsible for the decarboxylation of 
L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) and is the final step 
in dopamine synthesis. Dopamine is required in the brains of humans to develop motor function. 
Without adequate levels of AADC, children exhibit stunted motor development and fail to 
develop motor milestones. Patients with AADC deficiency require lifelong care and their 
condition does not improve without intervention. Current treatments for AADC deficiency 
alleviate symptoms, but do not address the underlying cause of the disease. 
Eladocagene exuparvovec is designed to increase levels of AADC within target areas of the 
brain, with the goal of restoring levels of dopamine. In children, dopamine signaling is required 
to develop motor skills in a sequential fashion. This study will evaluate the increase in HVA 
levels as an indication of dopamine increase following eladocagene exuparvovec treatment. 
The safety and efficacy of eladocagene exuparvovec has been established in 3 clinical studies 
using a stainless-steel cannula. This study will evaluate the administration of eladocagene 
exuparvovec to pediatric subjects using the SmartFlow MR-compatible ventricular cannula, 
which will allow for intraoperative MRI (if required) to assist in guidance of gene therapy 
administration and has been used previously to administer viral vector to the brain of adult 
patients with Parkinson’s disease (Bankiewicz 2016). 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Primary Objectives 
The primary objectives of this study are as follows: 
• To assess the pharmacodynamics (PD) of eladocagene exuparvovec treatment by 
evaluation of HVA levels at 8 weeks after administration  
• To assess the safety of the SmartFlow MR-compatible ventricular cannula for 
administering eladocagene exuparvovec to pediatric subjects. 
2.2. 
Secondary Objectives 
The secondary study objectives of the study are as follows: 
• To assess the PD of eladocagene exuparvovec by evaluation of the following: 
− HVA at Week 48 
− PET at Weeks 8 and 48 
− 5-hydroxyindoleacetic acid [5-HIAA] at Weeks 8 and 48 
− 3-O-methyldopa [3-OMD]) at Weeks 8 and 48 
• To evaluate the long-term efficacy of eladocagene exuparvovec through Month 60 as 
assessed by the following: 
− Motor milestone attainment 
− PDMS-2 score 
− Bayley Scale of Infant Development, third edition (Bayley-III) 
− EQ-5D-Y 
− Body weight 
− AADC-specific symptoms 
• To evaluate the safety of eladocagene exuparvovec treatment as assessed by 
treatment-emergent adverse events (TEAEs), neurological examinations, MRI, and 
clinical laboratory tests. 
2.3. 
Primary Endpoints 
The primary efficacy endpoint is the change from baseline in HVA metabolite levels at the end 
of the Trial Phase (8 weeks after administration). 
The primary safety endpoint is the assessment of adverse events (AEs) associated with the 
surgical administration of eladocagene exuparvovec to pediatric subjects using the SmartFlow 
MR-compatible ventricular cannula at the end of Trial Phase (8 weeks after administration). 

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2.4. 
Secondary Endpoints 
The secondary endpoints are as follows: 
• Change from baseline in neurotransmitter CSF metabolite HVA (at 48 weeks after 
administration) 
• Change from baseline in PET imaging of putaminal-specific L-6-[18F] fluoro-3,4-
dihydroxyphenylalanine (18F-DOPA) PET uptake at the end of the Trial Phase 
(8 weeks after administration) and the Extension Phase (48 weeks after 
administration) 
• Change from baseline in neurotransmitter CSF metabolites 5-HIAA and 3-OMD at 8 
and 48 weeks after administration 
• Attainment of motor milestones 
• Motor development as assessed by the PDMS-2 
• Cognitive and language development as assessed by Bayley-III 
• Change in EQ-5D-Y 
• Change in body weight 
• Assessment of AADC-specific symptoms 
• Overall safety profile characterized by type, frequency, severity, timing, and 
relationship to study treatment of any TEAEs, neurological examination findings, 
brain imaging, or laboratory abnormalities. 

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3. 
STUDY DESCRIPTION 
3.1. 
Study Design 
This is an open-label study in subjects with AADC deficiency. At minimum, 3 eligible pediatric 
subjects will be enrolled and receive eladocagene exuparvovec at 1.8×1011 vg via SmartFlow 
MR-compatible ventricular cannula in a single operative session. Subjects will receive standard 
of care for their AADC deficiency during the study. Subjects will undergo Screening and a 
Baseline Visit before receiving eladocagene exuparvovec by intraputaminal infusion. A Data 
Safety Monitoring Board (DSMB) will conduct a review of safety data as outlined in the DSMB 
charter. Review by DSMB will not be required in order to enroll successive subjects. The DSMB 
will monitor ongoing study results to ensure subject well-being, safety, and study integrity. 
Subjects will return for regular visits during the course of the study. The length of the study, 
including the Screening Window, is approximately 63 months (approximately 5 years).  
This study’s Trial Phase, Extension Phase, and Long-Term Extension Phase are described as 
follows: 
• The primary objectives of the Trial Phase are to assess:  
− the PD of eladocagene exuparvovec treatment by evaluation of HVA levels at 
8 weeks after administration  
− the safety of the SmartFlow MR-compatible ventricular cannula for administering 
eladocagene exuparvovec to pediatric subjects with AADC deficiency. 
• The secondary objectives of the Trial Phase are to further assess the PD of 
eladocagene exuparvovec in subjects with AADC deficiency to further assess the PD 
of eladocagene exuparvovec in subjects with AADC deficiency using 
neurotransmitter metabolite assessment and PET analysis. 
• The Extension Phase is designed to capture additional clinical information for 
eladocagene exuparvovec through study evaluations, changes in motor development, 
AADC-specific- symptoms, and other PD measures. The Extension Phase will be 
complete at 48 weeks after administration of eladocagene exuparvovec. The 
additional study evaluations will be assessed as shown in the Schedule of Events in 
Table 1 and Table 2. 
• The Long-Term Extension Phase is designed to capture long-term safety and efficacy 
data, from subjects treated with eladocagene exuparvovec, through Month 60. Study 
evaluations for this Phase will be assessed as shown in the Schedule of Events in 
Table 3. 
3.2. 
Justification of Dose 
Strong nonclinical data in nonhuman primate models of Parkinson's disease and clinical data in 
patients with Parkinson's disease with rAAV2-hAADC vectors delivered to the putamen were 
used to guide the dose selection for a one-time administration of eladocagene exuparvovec for 
treating AADC deficiency. The intended dose of 1.8×1011 vg balances positive efficacy 
assessments with safety, as evidenced by the results from the 3 clinical studies. 

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Intrastriatal (caudate/putamen) and intraputaminal (putamen only) delivery of rAAV2-hAADC 
vectors in a nonhuman primate model of Parkinson’s disease resulted in AADC protein 
expression and improvements in response to L-DOPA therapy as evaluated by neurological 
function (Muramatsu 2002). Doses tested in the different studies were from 6×109 to 
3.6×1011 vg. Forsayeth and colleagues assessed multiple doses within a single preclinical 
Parkinson’s disease study (Forsayeth 2006). They evaluated the relationship between 
rAAV2-hAADC dose infused into the putamen and efficacy, including AADC enzyme activity in 
hemiparkinsonian monkeys. 
The doses tested ranged from 6×109 to 5×1011 vg. The study found that vector dose produced a 
linear increase in AADC enzyme activity in brain tissue at doses <5.5×1010 vg followed by a 
plateau starting at dose 1.7×1011 vg, indicating a saturation phenomenon in which higher doses 
showed little additional AADC enzyme activity. These results suggest that doses above 
1.7×1011 vg produce little additional increase in expression of rAAV2-hAADC transgene 
(Forsayeth 2006). In the context in which there are no demonstrable gains in efficacy at higher 
doses, it becomes imperative to ensure safety. 
Based on the dose response efficacy observed in nonhuman primate Parkinson’s disease studies, 
rAAV2-hAADC was subsequently tested in the first-in-human clinical trials of patients with 
Parkinson’s disease at dose levels of 9×1010 and 3×1011 vg via bilateral intraputaminal dosing 
(Christine 2009, Muramatsu 2010). Both doses were biologically active and well tolerated 
(Christine 2009). The prior findings in Parkinson’s disease patients were used to establish a dose 
that was expected to improve AADC activity in the putamen of children with AADC deficiency. 
The intended dose of 1.8×1011 vg is based on the fact that AADC activity and clinical benefit and 
safety have been demonstrated in 3 separate clinical studies with a follow-up of up to 9 years 
post administration of eladocagene exuparvovec. 
Eladocagene exuparvovec will be administered intraoperatively as a 1-time dose as four 
0.08 mL infusions at a dose of 0.45×1011 vg and a volume of 80 µL per site to 4 sites 
(2 per putamen), for the total dose of 1.8×1011 vg and a total volume of 320 µL per patient. 
3.3. 
End of Study Definition 
The end of study (Trial Phase, Extension Phase, and Long-Term Extension Phase) is defined as 
completion of assessments at the Month 60 Visit, or after follow-up for those subjects who 
complete the early termination (ET) visit or who decide to withdraw study consent. For subjects 
that terminate the study before the Week 48 visit, the ET Visit will be completed and will include 
all assessments required at the Week 48 visit.  For subjects that terminate the study after the 
Week 48 visit, but prior to the Month 60 Visit, the ET Visit will be completed and will include 
all assessments required at the Month 60 Visit. 

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4. 
STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects will be included if all the following inclusion criteria are fulfilled: 
1. Pediatric subjects must have genetically confirmed AADC deficiency with typical 
clinical characteristics and decreased AADC enzyme activity in plasma. 
2. Age range from 1 year to <18 years. 
3. Cranium sufficiently developed to allow placement of ClearPoint system for stereotactic 
surgery. 
4. Persistent neurological defects secondary to AADC deficiency despite standard medical 
therapy (dopamine agonists, monoamine oxidase inhibitor, pyridoxine, or other forms of 
vitamin B6) in the opinion of the investigator. 
5. Unable to ambulate independently (with or without assistive device). 
6. Baseline hematology, chemistry, and coagulation values within the normal pediatric 
laboratory value ranges, unless in the investigator’s opinion the out-of-range values are 
not clinically significant with respect to the subject’s suitability for surgery. 
7. Subject must test negative for coronavirus disease of 2019 (COVID-19) a maximum of 
72 hours prior to receiving gene therapy. 
Note: If a subject tests positive for COVID-19 at the Screening or Baseline Visit, he/she 
will need to have negative test results for 2 weeks (2 weeks since the last positive test 
result and 2 negative test results a minimum of 14 days apart, with second negative test 
result no more than 72 hours prior to surgery) before receiving gene therapy. If a 
COVID-19 test is administered per site policy within 72 hours of the Screening Visit, the 
results may be used for the AADC-GT-002 study. The COVID-19 test does not need to 
be repeated after the COVID-19 pre-consent is signed. 
8. Subject must be on stable dosage for 3 months prior to baseline for all medications 
related to treatment of AADC deficiency, including dopamine agonists, monoamine 
oxidase inhibitors, anticholinergic drugs, and vitamin B6. 
9. Females of childbearing potential must have a negative pregnancy test at screening and 
baseline and agree to abstinence or double-barrier form of contraception for the duration 
of the study following discharge from the hospital (acceptable methods will be 
determined by the site). 
10. Males sexually active with females of childbearing potential must agree to use a barrier 
method of birth control during the study following discharge from the hospital. 
11. Parent(s)/legal guardian(s) with custody of the subject must agree to comply with the 
requirements of the study, including the need for frequent and prolonged follow-up. 
12. Parent(s)/legal guardian(s) with custody of the subject must give their consent for subject 
to enroll in the study. 

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4.2. 
Exclusion Criteria 
1. The subject has presence of other significant medical or neurological conditions that 
would create an unacceptable operative or anesthetic risk. 
2. Subjects with pyridoxine 5'-phosphate oxidase or tetrahydrobiopterin (BH4) deficiency. 
3. Contraindication for imaging studies (computed tomography [CT] scan, PET, or MRI), 
including sedation limitations or metal that would interfere with a brain MRI. 
4. Anti-AAV2 antibody titer higher than 1:1200 or >1 optical density value by enzyme-
linked immunosorbent assay. 
5. Subjects that have received treatment with other experimental therapies within the last 
24 weeks prior to planned gene therapy administration, or any treatment ever with a gene 
therapy. 
6. Evidence of a clinically active infection. 
7. Females who are pregnant or breast feeding. 
4.3. 
Screen Failures 
Only subjects who fail screening assessments/procedures due to a positive COVID-19 test will 
be permitted to rescreen. 
If a subject withdraws consent prior to dosing, he or she may rescreen at a later date after the 
investigator’s discussion with the PTC medical monitor. 

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5. 
STUDY INTERVENTION 
The eladocagene exuparvovec nonclinical program consists of proprietary studies, including 
in vitro studies in human cells, as well as relevant supportive literature information that explored 
efficacy studies in a mouse model of AADC deficiency and rat and nonhuman primate models of 
Parkinson’s disease. Details of these studies and the selection of the intraputaminal route of 
administration are provided in Section 4 of the Investigator’s Brochure (IB). 
See the Surgical Manual for a complete description of the surgical procedure. 
5.1. 
Study Intervention Description 
Eladocagene exuparvovec is a recombinant non-replicating AAV2 vector comprising a human 
DDC (also referred to as AADC) cDNA transcript, which encodes hAADC, under the control of 
the cytomegalovirus immediate-early promoter (CMV IEP) and simian virus 40 polyadenylation 
transcription terminator (Figure 1). 
Figure 1: 
Diagram of Eladocagene Exuparvovec Expression Cassette 
 
Abbreviations: CMV IEP, cytomegalovirus immediate-early promoter; hAADC, human aromatic L-amino acid 
decarboxylase; HBG2/3, human β globin partial intron 2/partial exon 3; ITR, inverted terminal repeat; 
Poly A, polyadenylation sequence 
Note: Genetic elements are drawn to approximate proportions. 
Source: Eladocagene exuparvovec IB, Figure 1 
Eladocagene exuparvovec is formulated in a sterile solution containing standard compendial 
excipients. 
5.2. 
Dosing and Administration 
Subjects will receive eladocagene exuparvovec intraoperatively as a 1-time dose as four 0.08 mL 
infusions at a dose of 0.45×1011 vg and a volume of 80 µL per site to 4 sites (2 per putamen), for 
the total dose of 1.8×1011 vg and a total volume of 320 µL per subject. Administration of gene 
therapy is described in the Surgical Manual. 
5.3. 
Preparation/Handling/Storage/Accountability 
5.3.1. 
Preparation and Handling 
Details pertaining to the preparation and handling of eladocagene exuparvovec are provided in 
the Pharmacy Manual. 

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5.3.2. 
Storage 
Eladocagene exuparvovec will be stored at ≤-65°C. Study personnel must ensure that all 
eladocagene exuparvovec drug product is kept in a temperature monitored secure locked area 
with access limited to authorized personnel. Temperature excursions must be reported 
immediately, and product must be quarantined while awaiting disposition confirmation from the 
sponsor. 
5.3.3. 
Accountability 
Gene therapy will be administered on a one-time basis by a neurosurgeon. 
The investigator/site personnel and/or central pharmacy must maintain accurate records of the 
receipt of all gene therapy shipped by PTC Therapeutics (PTC), or its designee, including, but 
not limited to, the date received, lot number, amount received, and the disposition of all gene 
therapy product. Drug accountability records must also be maintained by the site and central 
pharmacy that include the subject’s assigned study number, date and amount of gene therapy 
dispensed, and relevant kit and lot numbers. 
5.3.4. 
Formulation, Appearance, Packaging, and Labeling 
Eladocagene exuparvovec is an AAV2 capsid containing the expression cassette with the hAADC 
gene of interest (see Section 5.1). The final commercial formulation of eladocagene exuparvovec 
will be used in this study. The drug product is comprised of compendial excipients including 
potassium chloride, sodium chloride, potassium dihydrogen phosphate, disodium hydrogen 
phosphate, and poloxamer 188 in Water for Injection, pH 6.9. 
Additional details can be found in the IB and the Pharmacy Manual. 
5.4. 
Concomitant Therapy 
Other than the gene therapy, any treatments (including prescription and non-prescription drugs, 
health foods, herbal remedies, or self-prescribed drugs) that are taken by a subject during the 
Screening Window, during gene therapy administration, and for the remainder of the study are 
considered concomitant medications. Information regarding any concomitant medications will be 
collected and documented in the electronic case report form (eCRF) and in the source documents 
by the clinic staff. 
To the extent possible, administration of any prescription or over-the-counter drug products other 
than study medication should be minimized during the study period. Subjects should be 
discouraged from use of “health supplements” (eg, creatine, glutamine), herbal remedies, growth 
hormone, or self-prescribed drugs at any time during this clinical study of eladocagene 
exuparvovec. Blood thinners should not be used 7 days prior to the surgical procedure. 
Any medication that may affect the result evaluation of trials cannot be used during the trial 
stage. 
All medications related to the treatment of AADC deficiency, including dopamine agonists, 
monoamine oxidase inhibitors, anti-cholinergic drugs, and vitamin B6, may be continued during 
the study provided that: 
• no changes in dosage for the 3 months prior to baseline 

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• change in the dosage during the duration of the trial is not anticipated, with the 
exception of an allowance for decrease in dosage or discontinuation in the setting of a 
hyperdopaminergic state. Dosing changes are made at the discretion of the 
investigator 
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator. The decision to 
authorize the use of any other drug(s) should consider the subject’s safety, the medical need, the 
potential for drug interactions, the possibility for masking symptoms of a more relevant 
underlying event, and whether use of a concomitant medication will compromise the outcome or 
integrity of the study. 
Subjects and parents/caregivers or legal guardian should be instructed about the importance of 
the need to inform the clinic staff of the use of any drugs or remedies (whether prescribed, 
over-the-counter, or illicit) before and during the course of the study. 
Vaccination for COVID-19 is permissible as a concomitant medication under the following 
conditions: 
• The subject must wait 1 month after the final dose of vaccine prior to receiving 
eladocagene exuparvovec. 
• Once the subject has been dosed with eladocagene exuparvovec, it is recommended 
that he/she waits 3 months from the date of eladocagene exuparvovec administration 
before receiving the vaccine. 
Vaccine information should be recorded with the subject’s concomitant medications. 
The investigator is encouraged to consult the PTC medical monitor or designee with questions 
relating to specific drugs and their potential for interactions with eladocagene exuparvovec. 
5.5. 
Organ Donation 
Subjects may not donate blood, organs, tissues, or fluids at any time during the study or after the 
study has been completed. 

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6. 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL 
6.1. 
Stopping Rules 
The procedure will be discontinued in the event of any occurrence that would potentially lead to 
intraoperative or postoperative complications or increased risk of subject harm. 
At the subject level, the occurrence of any of the following events, regardless of causality, would 
lead to discontinuation of the procedure for any subject: 
• Anesthesia complications 
• Intracerebral hemorrhage demonstrated on imaging during the procedure 
• Hemodynamic instability during the procedure 
• Equipment malfunction 
• Presence of a clinically significant CSF leak, in the opinion of the investigator, during 
the study procedure 
At the study level, the occurrence of any of the following events, regardless of causality, would 
lead to halting of study enrollment: 
• Any symptomatic intracerebral hemorrhage or stroke that results in a significant new 
neurologic deficit that persists one month following surgery 
• Clinically significant CSF leak, in the opinion of the investigator 
• Any central nervous system infections related to study interventions 
• Dyskinesias severe enough to require intensive care unit (ICU) admission for greater 
than 30 days 
• Any death 
If any of these events occur, no further subjects will receive treatment until a comprehensive 
safety review has been completed by the DSMB and PTC. The United States Food and Drug 
Administration (FDA) and/or applicable country health authority(ies), Institutional Review 
Boards (IRBs), Institutional Ethics Committees, and the Institutional Biosafety Committee will 
be promptly notified. 
6.2. 
Participant Discontinuation/Withdrawal from the Study 
This study features a one-time administration of gene therapy via surgical procedure. Subjects 
may discontinue from the study at any time. 
If it is determined by the investigator that any subject will discontinue the study, all ET Visit 
procedures should be completed according to Table 2 for the Extension Phase and Table 3 for the 
Long-Term Extension Phase, and the Final Visit should be captured as ET in an eCRF. If it is 
determined that a subject will discontinue the study in between visits, the subject should return at 
their earliest convenience for an ET Visit to complete any required study assessments. The PTC 
medical monitor should be informed within 24 hours of the investigator being made aware of the 
subject’s discontinuation of the study via e-mail. 

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Subjects who terminate the study early will not be replaced. 
• All subjects who receive eladocagene exuparvovec should remain in the study for the 
duration of the study. However, the subject, parent/caregiver, or legal guardian has 
the right to withdraw consent and discontinue the study at any time. 
A subject may withdraw/discontinue under the following conditions/events: 
• The occurrence of a clinically significant worsening of disease status or change in a 
laboratory parameter that may place the subject at risk. 
• The occurrence of a SAE. 
• The occurrence of a protocol violation, if it interferes with the safety of a subject or 
data integrity. 
• Upon consultation with the PTC medical monitor, the investigator may withdraw the 
subject from the study if, in the investigator’s clinical judgment, it is not in the 
subject’s best interest to continue. 
• This study may be discontinued by the relevant regulatory authority, 
IRB/Independent Ethics Committee (IEC), and/or PTC at any time. 
6.3. 
Lost to Follow-Up 
Subjects are considered lost to follow-up if the subject does not return to the clinic and attempts 
to contact the subject or subject’s parent/caregiver/legal guardian are unsuccessful. The site 
should make every effort to avoid any subject being lost to follow-up during the study. Before 
subjects are considered lost to follow-up, a minimum of 2 documented telephone contact 
attempts and 1 certified letter within 6 weeks of the most recent planned study visit must be sent 
in efforts to contact the subject/caregiver/legal guardian. After being considered lost to follow-
up, a subject’s status may be changed if the subject/caregiver/legal guardian makes contact at a 
later time provided the trial is ongoing. 

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7. 
STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Schedule of Events and Study Parameters 
Table 1: 
Schedule of Events for Trial Phase 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Type of Visit  
(In-Person or Phone) 
In-Person 
In-Person 
In-Person 
In-Person 
Phone 
In-Person 
Phone 
Phone 
In-Person 
Visit Windowa 
W-10 to -2 BL W-1 
Dosing 
Day (D1)c 
Disc (D3) 
W2 
W3 
W4 
W6 
W8 
Screeningb ±3D 
 
+4D 
±2D 
±3D 
±2D 
±2D 
±3D 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Genetic testingd,e,f 
X 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
COVID-19 testg 
X 
X 
X 
 
 
 
 
 
 
Pregnancy testh 
X 
X 
X 
 
 
X 
 
 
X 
AADC enzyme activity 
assessmentf 
X 
 
 
 
 
 
 
 
 
Collect CSF historyi 
X 
 
 
 
 
 
 
 
 
CSF neurotransmitter 
analysisf,j,k 
 
 
Xj,m,o 
 
 
 
 
 
Xj,o 
Anti-AAV2 antibody 
(IgG and neutralizing titers)f 
X 
 
Xl 
X 
 
X 
 
 
X 
Viral shedding (blood and 
urine)f,n 
 
 
Xl 
X 
 
X 
 
 
X 
Viral shedding (CSF)f,j 
 
 
Xj,m,o 
 
 
 
 
 
Xj,o 
Physical examinationp 
X 
X 
X 
X 
 
X 
 
 
X 
Vital signsq 
X 
X 
X 
X 
 
X 
 
 
X 
Height/weight 
X 
X 
X 
X 
 
X 
 
 
X 
Brain MRI (T1-MPRAGE and 
T2-FLAIR sequences)j,o 
Xr 
 
 
Xs 
 
Xs 
 
 
Xs 
Real-time intrasurgical MRI 
 
 
X 
 
 
 
 
 
 
Postdose brain CTt 
 
 
X 
 
 
 
 
 
 
Brain 18F-DOPA PETj,o,u 
 
X 
 
 
 
 
 
 
X 
Chest x-rayv 
 
X 
 
 
 
 
 
 
 
12 lead ECG 
 
X 
 
 
 
 
 
 
 

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Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Type of Visit  
(In-Person or Phone) 
In-Person 
In-Person 
In-Person 
In-Person 
Phone 
In-Person 
Phone 
Phone 
In-Person 
Visit Windowa 
W-10 to -2 BL W-1 
Dosing 
Day (D1)c 
Disc (D3) 
W2 
W3 
W4 
W6 
W8 
Screeningb ±3D 
 
+4D 
±2D 
±3D 
±2D 
±2D 
±3D 
Oculogyric crisis eDiary 
instructions for usew 
X 
 
 
 
 
 
 
 
 
AADC-specific symptomsx 
X 
X 
 
X 
 
X 
 
 
X 
Laboratory testsy 
X 
X 
 
X 
 
X 
 
 
X 
T-cell sample collection 
X 
 
X 
X 
 
X 
 
 
X 
PDMS-2 
 
X 
 
 
 
 
 
 
 
Bayley-III 
 
X 
 
 
 
 
 
 
 
EQ-5D-Yz 
 
X 
 
 
 
 
 
 
 
Study drug injection 
(eladocagene exuparvovec) 
 
 
X 
 
 
 
 
 
 
AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 3-OMD, 3-O-methyldopa; 5-HIAA, 5-hydroxyindoleacetic acid; 18F-DOPA, fluoro-3,4-dihydroxyphenylalanine; AADC, aromatic L-amino acid 
decarboxylase (deficiency); AAV2, adeno-associated virus, serotype 2; AE, adverse event; aPTT, activated partial thromboplastin time; BL, Baseline; Bayley-III, 
Bayley Scale of Infant Development, third edition; CBC, complete blood count; CMP, comprehensive metabolic panel; COVID-19, coronavirus disease of 2019; 
CSF, cerebrospinal fluid; CT, computed tomography; D, day; diff, differential count; Disc, discharge; ECG, electrocardiogram; eDiary, electronic diary; 
HVA, homovanillic acid; ICU, intensive care unit; IgG, immunoglobulin G; INR, international normalized ratio; L-DOPA, L-3,4-dihydroxyphenylalanine; 
MHPG, 3-methoxy-4-hydroxyphenylglycol; MRI, magnetic resonance imaging; OGC, oculogyric crisis; PDMS-2, Peabody Developmental Motor Scale, second 
edition; PET, positron emission tomography; PI, principal investigator; PT, prothrombin time; PTT; partial thromboplastin time; RBC, red blood cell (count); 
T1-MPRAGE, T-1 weighted magnetization prepared rapid gradient echo; T2-FLAIR, T2-weighted fluid-attenuated inversion recovery; W, week; WBC, white blood 
cell (count) 
a Any study visit may take place over a 3-day period, as necessary. 
b Screening will be conducted and completed up to 9 weeks prior to the Baseline Visit. Subjects who are unable to adhere to the Screening Visit window specified 
in the protocol due to unforeseen circumstances (eg, COVID-19) may be rescreened upon sponsor approval. If the Baseline Visit does not occur within 9 weeks 
after the Screening Visit per the Screening Window, the only Screening Visit assessments that need to be performed again are the local laboratory assessments, 
physical exam, and vital signs. 
c Surgical procedure will require a minimum of 1 night in the ICU and hospitalization for up to 3 days. Subjects will be required to stay in the vicinity of the study 
clinic for a minimum of 7 days total post procedure. 
d If historic AADC diagnosis clinical testing results are available, they may be used to determine eligibility. If historic AADC diagnosis clinical testing results are 
used to determine eligibility, AADC diagnosis clinical testing does not need to be repeated at Screening. 
e If historic enzyme results are available, they may be used to determine eligibility. If historic enzyme results are used to determine eligibility, enzyme testing does 
not need to be repeated at Screening. 
f Analyzed by a Central Laboratory. 
g Subjects must pre-consent and have a negative COVID-19 test prior to the Screening Visit. Subject must test negative for COVID-19 a maximum of 72 hours 
prior to receiving gene therapy. If a subject tests positive for COVID-19 at the Screening or Baseline Visit, he/she will need to have negative test results for 2 
weeks (2 weeks since the last positive test result and 2 negative test results a minimum of 14 days apart, with the second negative test result no more than 72 

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hours prior to surgery) before receiving gene therapy. If a COVID-19 test is administered per site policy within 72 hours of the Screening Visit, the results may be 
used for the AADC-GT-002 study. The COVID-19 test does not need to be repeated after the COVID-19 pre-consent is signed. 
h Females of childbearing potential only. The pregnancy test can be collected via urine or serum, at the discretion of the PI. Will be assessed by a local laboratory. 
i CSF analysis history (check only HVA/5-HIAA/3-OMD/pterins/MHPG/L-DOPA/5-HTP) to be collected if available. 
j Subjects may be admitted to the hospital and sedation may be used at the discretion of the PI. 
k CSF analysis items (HVA/5-HIAA/3-OMD and cell count [appearance, RBC, WBC, protein, and glucose]). 
l Sample should be collected predose on day of surgery. 
m CSF sample will be collected predose during the surgical procedure for the purposes of assessing viral shedding and neurotransmitter analysis. 
n Urine should be collected using a clean catch or catheter and stored in a sterile container. 
o Days that require imaging or lumbar puncture can be split into 3-day visits, if necessary, provided that all clinical assessments (Bayley-III, EQ-5D-Y, and 
PDMS-2) are completed prior to any other assessments on Days 1, 2, or 3 of the visits. 
p Complete physical examination at Screening, Baseline Visit, and on Dosing Day (D1), and targeted physical examination for all other visits. The complete 
physical examination will consist of an examination of the following: neurological assessment and assessments of general appearance, any changes to feeding 
tube placement or removal, skin, head, eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen, and extremities. The targeted 
physical examination will consist of a neurological assessment, general appearance assessment, any changes to feeding tube placement or removal, and heart 
auscultation. 
q Vital signs include temperature, pulse, respiratory rate, and blood pressure. 
r Brain MRI with gadolinium performed at Screening to exclude subjects who may have pre-existing conditions. 
s Brain MRI with gadolinium to check for persistent CSF leakage/fistula and inflammatory changes (eg, aseptic ventriculitis/meningitis). An MRI should be 
performed immediately if a CSF leak is suspected. 
t Brain CT for postdose hemorrhage check should be performed within 6 hours after the end of surgery. 
u PET scans will be centrally read. 
v P-A and lateral chest x-ray. 
w Parent/caregiver must complete eDiary or paper diary for each OGC occurrence throughout the Trial Phase and Extension Phase. In the event that the eDiary 
cannot be used, a paper version will be provided. 
x Findings for AADC-specific symptoms will be collected at every in-person visit after D1. These assess for floppiness (hypotonia), limb and stimulus-provoked 
dystonia, and muscle power. 
y Laboratory tests (PT; PTT or aPTT; INR; CBC w/diff; and CMP analysis [including total bilirubin]). These will be assessed by a local laboratory. 
z The EQ-5D-Y will not be administered to subjects under 4 years of age. If the subject turns 4 during the study, the caregiver will complete the EQ-5D-Y per 
protocol after the subject turns 4. 

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Table 2: 
Schedule of Events for Extension Phase 
Visit 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Type of Visit (In-Person or 
Phone) 
Phone 
In-
Person 
Phone 
Phone 
In-
Person 
Phone 
Phone 
In-
Person 
Phone 
Phone 
In-
Person 
Visit Windowa 
W10 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
W48/ETb 
±2D 
±3D 
±2D 
±2D 
±3D 
±2D 
±2D 
±3D 
±2D 
±2D 
±3D 
Pregnancy Testc 
 
X 
 
 
X 
 
 
X 
 
 
X 
CSF neurotransmitter analysis d,e,f  
 
 
 
 
 
 
 
 
 
X 
Anti-AAV2 antibody 
(IgG and neutralizing titers)d 
 
X 
 
 
X 
 
 
X 
 
 
X 
Viral shedding (blood and urine)d,g  
X 
 
 
X 
 
 
X 
 
 
X 
Viral shedding (CSF)d,e,f 
 
 
 
 
 
 
 
 
 
 
X 
Physical examinationh 
 
X 
 
 
X 
 
 
X 
 
 
X 
Vital signsi 
 
X 
 
 
X 
 
 
X 
 
 
X 
Height/weight 
 
X 
 
 
X 
 
 
X 
 
 
X 
Brain MRI  
(T1-MPRAGE and T2-FLAIR 
sequences)e,j,k  
 
 
 
 
 
 
 
 
 
X 
Brain 18F-DOPA PETe,j,l 
 
 
 
 
 
 
 
 
 
 
X 
AADC-specific symptomsm 
 
X 
 
 
X 
 
 
X 
 
 
X 
Laboratory testsn 
 
X 
 
 
X 
 
 
X 
 
 
X 
T-cell sample collection 
 
X 
 
 
X 
 
 
X 
 
 
X 
PDMS-2 
 
 
 
 
Xo 
 
 
 
 
 
Xo 
Bayley-III 
 
 
 
 
X 
 
 
 
 
 
X 
EQ-5D-Yp 
 
 
 
 
X 
 
 
 
 
 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations 3-OMD, 3-O-methyldopa; 5-HIAA, 5-hydroxyindoleacetic acid; 18F-DOPA, fluoro-3,4-dihydroxyphenylalanine; AADC, aromatic L-amino acid 
decarboxylase (deficiency); AAV2, adeno-associated virus, serotype 2; AE, adverse event; aPTT, activated partial thromboplastin time; Bayley-III, Bayley Scale of 
Infant Development, third edition; CBC, complete blood count; CMP, comprehensive metabolic panel; CSF, cerebrospinal fluid; D, day; diff, differential count; 
ET, early termination; HVA, homovanillic acid; INR, international normalized ratio; IgG, immunoglobulin G; MRI, magnetic resonance imaging; PDMS-2, Peabody 
Developmental Motor Scale, second edition; PET, positron emission tomography; PI, principal investigator; PT, prothrombin time; PTT; partial thromboplastin time; 
RBC, red blood cell (count); T1-MPRAGE, T-1 weighted magnetization prepared rapid gradient echo; T2-FLAIR, T2-weighted fluid-attenuated inversion recovery; 
W, week; WBC, white blood cell (count) 
a Any study visit may take place over a 3-day period, as necessary. 
b For subjects that terminate the study before the Week 48 visit, all assessments noted in the Week 48 visit will need to be completed. 
c Females of childbearing potential only. The pregnancy test can be collected via urine or serum, at the discretion of the PI. Will be assessed by a local laboratory. 
d Analyzed by a Central Laboratory. 
e Subjects may be admitted to the hospital and sedation may be used at the discretion of the PI. 
f CSF analysis items (HVA/5-HIAA/3-OMD and cell count [appearance, RBC, WBC, protein, and glucose]). 

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g Urine should be collected using a clean catch or catheter and stored in a sterile container. 
h Complete physical examination at Screening, Baseline Visit, and on Dosing Day (D1) and targeted physical examination for all other visits. The complete physical 
examination will consist of an examination of the following: neurological assessment and assessments of general appearance, any changes to feeding tube 
placement or removal, skin, head, eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen, and extremities. The targeted physical 
examination will consist of a neurological assessment, general appearance assessment, any changes to feeding tube placement or removal, and heart 
auscultation. 
i Vital signs include temperature, pulse, respiratory rate, and blood pressure. 
j Days that require imaging or lumbar puncture can be split into 3-day visits if necessary, provided that all clinical assessments (Bayley-III, EQ-5D-Y, and PDMS-2) 
 are completed prior to any other assessments on Days 1, 2, or 3 of the visits. 
k Brain MRI with gadolinium to check for persistent CSF leakage/fistula and inflammatory changes (eg, aseptic ventriculitis/meningitis). An MRI should be 
performed immediately if a CSF leak is suspected. 
l PET scans will be centrally read. 
m Findings for AADC-specific symptoms will be collected at every in-person visit. These assess for floppiness (hypotonia), limb and stimulus-provoked dystonia, 
and muscle power. 
n Laboratory tests (PT; PTT or aPTT; INR; CBC w/diff; and CMP analysis [including total bilirubin]). These will be assessed by a local laboratory. 
o Administer at approximately the same time of day as the baseline test was administered. 
p The EQ-5D-Y will not be administered to subjects under 4 years of age. If the patient turns 4 during the study, the caregiver will complete the EQ-5D-Y per 
protocol after the patient turns 4. 

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Table 3: 
Schedule of Events for Long-Term Extension Phase 
Visit 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
Type of Visit (In-Person or 
Phone) 
Phone In-
Person 
Phone In-
Person 
Phone 
In-Person Phone 
In-Person Phone 
In-Person 
Visit Windowa 
W60 
W72 
W84 
W96 
W130 
Month 30 
W156 
Month 36 
W182 
Month 42 
W208 
Month 48 
W234 
Month 54 
W260 
Month 60 
ETb/EOS 
±2D 
±3D 
±2D 
±2 weeks ±2 weeks ±6 weeks ±2 weeks ±6 weeks ±2 weeks ±6 weeks 
Pregnancy Testc 
 
X 
 
X 
 
X 
 
X 
 
X 
Physical examinationd 
 
X 
 
X 
 
X 
 
X 
 
X 
Vital signse 
 
X 
 
X 
 
X 
 
X 
 
X 
Height/weight 
 
X 
 
X 
 
X 
 
X 
 
X 
AADC-specific symptomsf 
 
X 
 
X 
 
X 
 
X 
 
X 
Laboratory testsg 
 
 
X 
 
X 
 
X 
 
X 
PDMS-2 
 
Xh 
 
Xh 
 
Xh 
 
Xh 
 
Xh 
Bayley-III 
 
X 
 
X 
 
X 
 
X 
 
X 
EQ-5D-Yi 
 
X 
 
X 
 
X 
 
X 
 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 3AADC, aromatic L-amino acid decarboxylase (deficiency); AE, adverse event; aPTT, activated partial thromboplastin time; Bayley-III, Bayley 
Scale of Infant Development, third edition; CBC, complete blood count; CMP, comprehensive metabolic panel; D, day; diff, differential count; ET, early termination; 
PDMS-2, Peabody Developmental Motor Scale, second edition; PI, principal investigator; PT, prothrombin time; PTT; partial thromboplastin time; RBC, red blood 
cell (count); W, week; WBC, white blood cell (count) 
a All visits may take place over a 7-day period, as necessary.  
b For subjects who terminate the study before the Month 60 visit, but after the W48 visit, all assessments noted in the Month 60 visit will need to be completed. 
c Females of childbearing potential only. The pregnancy test can be collected via urine or serum, at the discretion of the PI. Will be assessed by a local laboratory. 
d Complete physical examination at Weeks 96, 156, 208, and 260/ET and targeted physical examination at Week 72. The complete physical examination will 
consist of an examination of the following: neurological assessment and assessments of general appearance, any changes to feeding tube placement or removal, 
skin, head, eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen, and extremities. The targeted physical examination will consist 
of a neurological assessment, general appearance assessment, any changes to feeding tube placement or removal, and heart auscultation. 
e Vital signs include temperature, pulse, respiratory rate, and blood pressure. 
f Findings for AADC-specific symptoms will be collected at every in-person visit. These assess for floppiness (hypotonia), limb and stimulus-provoked dystonia, and 
muscle power. 
g Laboratory tests (PT; PTT or aPTT; INR; CBC w/diff; and CMP analysis [including total bilirubin]). These will be assessed by a local laboratory. 
h Administer at approximately the same time of day as the baseline test was administered. 
i The EQ-5D-Y will not be administered to subjects under 4 years of age. If the patient turns 4 during the study, the caregiver will complete the EQ-5D-Y per 
protocol after the patient turns 4. 

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7.2. 
Primary Endpoints 
7.2.1. 
HVA Levels 
The precursor L-DOPA is decarboxylated by AADC to form dopamine. After action at the nerve 
synapse, dopamine is reabsorbed into the presynaptic nerve terminal where it can either be 
repackaged into vesicles for future neurotransmitter release or metabolized to HVA. In the 
presence of AADC deficiency, the HVA level in the CSF is very low or below the limit of 
detection due to the abnormally low dopamine production. Upon restoration of AADC activity, 
as premised with gene therapy, dopamine levels increase due to a now functioning DDC gene 
and the concentration of HVA in the CSF rises. Thus, HVA can serve as an acceptable 
measurement of dopamine production as a result of AADC activity (Hyland 2006, Hyland 2007). 
7.2.2. 
Safety of Surgical Administration Using the SmartFlow Cannula 
Adverse events associated with the surgical administration of eladocagene exuparvovec to 
pediatric subjects using the SmartFlow MR-compatible ventricular cannula that occur during the 
Trial Phase will be collected as described in Table 1. 
7.3. 
Secondary Endpoints 
7.3.1. 
18F-DOPA Positron Emission Tomography 
Expression and activity of the AADC enzyme in the putamen will be assessed by PET imaging 
using 18F-DOPA, a positron-emitting fluorine-labeled version of levodopa, which is a substrate 
for AADC that is incorporated into de novo dopamine. When 18F-DOPA is administered 
intravenously, it crosses the blood-brain barrier and is taken up by presynaptic nigrostriatal 
dopaminergic neurons in the putamen and converted by AADC to dopamine (Firnau 1987). 
Therefore, increased 18F-DOPA putamen uptake over time objectively demonstrates in vivo 
newly produced dopamine, and thus the presence of functional AADC enzyme. 
18F-DOPA will be infused during the procedure. In this study, a total dose of 18F-DOPA will be 
administered consistent with the recommendations of the European Association of Nuclear 
Medicine task force and the prescribing information for DOPAVIEW. A weight-based dosage 
table is included in the Procedure Manual for PET Imaging of the Brain. A weight-based dose 
should be administered based on guidance in this table. Ninety minutes after injection of 
18F-DOPA, a 15-minute static acquisition will be obtained with a PET/CT scanner. The PET 
scanner detects positron emission radioactivity from 18F-DOPA uptake, and the CT image 
provides brain anatomy; these images will be co-registered on the PET/CT scanner. PET 
imagining will be analyzed. 
The levels of 18F-DOPA radioactivity will be normalized by the injected dose and by subject 
weight and expressed as the standardized uptake value (SUV) using the open-source, free 
medical image viewer Horos (www.horosproject.org). Given that Swoboda and colleagues have 
previously reported that no 18F-DOPA PET uptake could be measured in a single patient with 
AADC deficiency, it was decided to measure the maximal SUV in all regions of interest as 
previously reported by Hwu et al rather than average SUV (Swoboda 2003, Hwu 2012). Regions 
of interest for the putamen will be a 1-cm2 circular area in the right and left putamen each, 
viewed on an axial plane. All values used will be the maximal SUV (SUVmax) for each brain 

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region described. The left and right putamen SUVmax will be subsequently averaged for a single 
putamen SUVmax measurement. The background brain radioactivity from any 18F-DOPA that 
may still be present in the vasculature within the brain tissues will be subtracted from the 
putamen measurement using the occipital measurement (control region). The background 
SUVmax in the control region occipital lobe will be calculated from a 5-cm2 area region of 
interest in the center of the occipital lobe. 
7.3.2. 
Peabody Developmental Motor Scale, Second Edition 
The PDMS-2 is a validated instrument used to measure motor skills and developmental 
milestone achievement in infants and children (Folio 2000). 
To optimize testing duration in this pediatric population, for all subtests except for Reflexes, the 
PDMS-2 administrator may begin testing at an entry point, which is a predetermined item that 
most of children in the healthy population are able to achieve at a given age. A basal level will 
then be determined, which is the point at which the subject achieves a score of 2 on 
3 consecutive skill items prior to achieving a 0 or 1 score on a skill item; all items below the 
basal level are scored as 2. Finally, a ceiling level is determined, which is the point at which the 
subject achieves a score of 0 on 3 consecutive skill items. All items above the ceiling are scored 
as 0, and the testing will be discontinued. 
The PDMS-2 instrument is scored by a qualified physiotherapist. Each skill item is assessed as a 
simple, 3-level scoring system as a consistent way of describing the child’s achievement of a 
particular motor skill, as listed below: 
0 = the skill is not met 
1 = the skill is emerging and shows a clear resemblance to mastery of the skill item 
2 = the child is mastering the motor skill 
A composite Gross Motor Quotient will be calculated from the scores on the Reflexes (8 skill 
items; age birth to 11 months), Stationary (30 skill items), Locomotion (89 skill items), and 
Object Manipulation (24 skill items; age 12 months and older) subscales. A composite Fine 
Motor Quotient will be calculated from the scores on the Grasping (26 skill items) and Visual 
Motor Integration (72 skill items) subscales. A Total Motor Quotient, which incorporates the 
results of both the Gross and Fine Motor Quotients, is considered the most complete evaluation 
of overall motor skills. 
The PDMS-2 motor skill items assess key motor milestones of 1) full head control, 2) sitting 
unassisted, 3) standing with support, and 4) walking assisted, which were chosen for further 
statistical assessments as these were the key motor milestones used to define the natural history 
of patients with AADC deficiency (Wassenberg 2017). There are several components of each 
motor skill that become progressively more difficult. The PDMS-2 motor skill items that were 
used to assess motor milestones are described below: 
• Full Head Control: A subject will be considered successful for Item 10 full head 
control if he/she achieves a score of 2 by sitting supported at his/her hips and holding 
his/her head aligned while rotating his/her head to follow a toy for 8 seconds, or if 
he/she achieves a score of 1 by sitting supported at his/her hips and holding his/her 
head aligned while rotating his/her head to follow a toy for 4 to 7 seconds. 

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• Sitting Unassisted: A subject will be considered successful in sitting unassisted if 
he/she achieves a score of 2 on Item 14 of the Stationary subtest, which requires the 
subject to sit without support and maintain balance while in a sitting position for 
60 seconds, or if he/she achieves a score of 1, which requires the subject to sit without 
support and maintain balance while in a sitting position for 30 to 59 seconds. 
• Standing with Support: A subject will be considered successful at stepping while 
standing with support if he/she achieves a score of 2 on Item 28 of the Locomotion 
(gross motor) subtest, which requires the subject to take at least 4 alternating steps, 
either in place or in forward motion, with the evaluator’s hands around the child’s 
trunk, consistent with standing with support, or if he/she achieves a score of 1, which 
requires the subject to take 2 to 3 alternating steps, either in place or in a forward 
motion, with the evaluator’s hands around the child’s trunk. 
• Walking Assisted: A subject will be considered successful at walking with assistance 
if he/she achieves a score of 2 on Item 34 of the Locomotion (gross motor) subtest, 
which requires the subject to walk at least 8 feet with alternating steps, with the 
examiner beside the subject and holding only one of the child’s hands, or if he/she 
achieves a score of 1, which requires the subject to walk 4 to 7 feet with alternating 
steps, with the examiner beside the subject and holding only one of the child’s hands. 
For each of these 4 key motor milestones, the numeric score of “2” will be translated into a 
“mastery,” indicating that the child achieved the milestone; the numeric score of “1” will be 
translated into “emerging”, indicating that the child showed emerging skill; a numeric score of 
“0” or “unscored” equated to “fail,” and therefore the subject did not achieve the milestone. 
PDMS-2 raw scores will be presented for this study. Normally, the raw scores are transformed 
relative to the subject’s age and measured against what is “normal” for that age. If scores are 
transformed, all the subjects with AADC deficiency would score markedly below their age range 
because of their development delays. 
The PDMS-2 score sheet is provided in Appendix 1. 
7.3.3. 
Bayley Scale of Infant Development, Third Edition 
The Bayley-III is a standardized assessment of cognitive, language, and motor development for 
children between 1 and 42 months of age. This measure consists of a series of developmental 
tasks. The Bayley-III has 3 main subscales, which are the Cognitive, Language, and Motor 
Scales. 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 Motor Scale assesses gross and fine motor skills such as 
grasping, sitting, stacking blocks, and climbing stairs. Only the Cognitive and Language scales 
from the Bayley-III will be used in this study, as the Bayley-III Motor Scale is largely 
duplicative of the primary efficacy evaluation (motor milestone achievement using the PDMS-2). 

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7.3.4. 
EQ-5D-Y 
The EQ-5D-Y is comprehensible instrument suitable for evaluating children and adolescents. 
The EQ-5D-Y descriptive system comprises the following 5 dimensions: mobility, looking after 
myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. A 
proxy version of the EQ-5D-Y will be provided by the site and administered by the caregiver. 
The caregiver will be asked to rate the child’s/adolescent’s health-related quality of life in the 
caregiver’s opinion. 
The EQ-5D-Y will not be administered to subjects under 4 years of age. If the subject turns 4 
during the study, the caregiver will complete the EQ-5D-Y per protocol after the subject turns 4. 
7.3.5. 
Body Weight 
Many subjects with AADC deficiency are reported to have feeding/swallowing difficulties and 
failure to thrive or gain weight as appropriate for growth (Wassenberg 2017). Therefore, the 
change in subjects’ body weights over time will be assessed as a supportive, exploratory measure 
of efficacy. 
7.3.6. 
AADC-Specific Symptoms 
Aromatic L-amino acid decarboxylase deficiency is characterized by specific neurological 
symptoms, including floppiness (hypotonia), oculogyric crisis (OGC) episodes, limb dystonia, 
and stimulus-provoked dystonia. These symptoms will be evaluated by the investigator as 
described in Table 1, Table 2, and Table 3. 
Detailed neurologic examinations, including assessments of muscle power, muscle tone, and 
spontaneous movement, will be performed as described in Table 1 and Table 2. 
Any OGC episodes and associated concomitant medications will be recorded throughout the 
Trial Phase and Extension Phase by caregivers using an electronic diary (eDiary) with 
prespecified questions. In the event that the eDiary cannot be used, a paper version of the diary 
will be provided. Oculogyric crisis episodes should be entered in the eDiary or paper diary when 
they occur. 
Muscle power will be measured in the following 4 areas: I (right upper extremity), II (left upper 
extremity), III (right lower extremity), and IV (lower left extremity). Muscle power is typically 
graded on a 6-point scale as follows: 
• 1, no movement 
• 2, trace of contraction 
• 3, active movement when gravity is eliminated 
• 4, active movement against gravity 
• 5, active movement against gravity and resistance 
• 6, normal strength 

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7.3.7. 
Measurement of 3-OMD and 5-HIAA 
Similar to L-DOPA, the precursor 5-HTP is decarboxylated by AADC to form serotonin. After 
action at the nerve synapse, serotonin is reabsorbed into the presynaptic nerve terminal where it 
can either be repackaged into vesicles or metabolized 5-HIAA. In the presence of AADC 
deficiency, the 3-OMD level in the CSF is increased and the 5-HIAA level is very low or below 
the limits of detection due to the abnormally low serotonin production. Upon restoration of 
AADC activity, concentrations of and 3-OMD levels decrease in the CSF and 5-HIAA rise 
(Hyland 2006, Hyland 2007). 
Neurotransmitter metabolites will be quantified following isocratic, reversed phase high 
performance liquid chromatography separation and coulometric electrochemical oxidation using 
EZChrom software. 
7.4. 
Home Care Services 
If for unforeseen reasons subjects are unable to travel to the study site, with approval from both 
the Principal Investigator and PTC medical monitor, they may be offered an opportunity to have 
study visits performed in their home. This applies to all visits, with the exception of Week 8 
(Visit 9), Week 48 (Visit 20), and all visits during the Long-Term Extension Phase which are 
critical in order to evaluate study endpoints and therefore must occur in the office. In order to 
conduct the home visits, the subject must agree to utilize home care services. A licensed nurse 
will then contact the subject to schedule visits. The home care nurse, the home care agency, and 
the home care services provider may have access to the subject’s personal data including their 
individually identifiable protected health information, such as the subject’s name, address, or 
phone number. This type of information will only be used as necessary to schedule and conduct 
the home visits and will not be provided to the sponsor. 
7.5. 
Safety Assessments 
7.5.1. 
Peri-Operative Safety Monitoring 
Subjects will have preoperative MRI with contrast to rule out any underlying condition that 
would pose a surgical safety risk or would reveal the subject to be unfit for study inclusion. 
Surgery will be performed following standard of care, including wound closure techniques and 
close monitoring of vital signs throughout the surgical procedure. Additionally, monitoring for 
intraoperative complications and AEs including anesthesia complications, intracerebral 
hemorrhage demonstrated on imaging during the procedure, CSF leak, hemodynamic instability 
during the procedure, or equipment malfunction will occur. 
Post-surgery, subjects will have monitoring in the ICU for a minimum of one night. Any 
autonomic dysfunction will be addressed aggressively. Subjects will be monitored on the 
neurosurgery ward for an additional one to 2 nights prior to discharge. Prior to discharge, 
subjects will undergo an MRI to evaluate for any evidence of swelling, bleeding, early signs of 
infection, CSF fistulas or leaks, inflammation, or other possible surgical complications. Subjects 
will only be discharged if they are tolerating oral intake, have resumed bowel and bladder 
function, and have good pain control. 
Subjects must reside within the vicinity of the hospital where the procedure was performed for a 
minimum of 7 days following the procedure. Subjects can be seen for an unscheduled visit, if 

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needed, to assess complications. A second follow-up visit will take place 2 weeks later 
(ie, 3 weeks after the surgery) to monitor post-surgical recovery, occurrence of AEs, and 
complete other study procedures. 
7.5.2. 
Adverse Events and Serious Adverse Events 
7.5.2.1. 
Definition of Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not it is considered related to the drug. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease in a study 
subject who is administered gene therapy in this study. 
For this protocol, untoward medical occurrences that should be reported as AEs include the 
following: 
• All AEs during the course of treatment with gene therapy administration. 
• All AEs resulting from medication errors such as dispensing or administration error 
outside of what is described in the protocol. 
• Apparently unrelated illnesses, including worsening of a pre-existing illness. 
• Injury or accidents. Note that if a medical condition is known to have caused the 
injury or accident (a fall secondary to dizziness), the medical condition (dizziness) 
and the accident (fall) should be reported as 2 separate AEs. The outcome of the 
accident (hip fracture secondary to the fall) should be recorded in source documents. 
• Abnormalities in physiological testing or physical examination findings that require 
clinical intervention or further investigation (beyond ordering a repeat [confirmatory] 
test). 
• Laboratory, echocardiogram, or electrocardiogram abnormalities that require clinical 
intervention or further investigation (beyond ordering a repeat [confirmatory] test) 
unless they are associated with an already reported clinical event. Laboratory 
abnormalities associated with a clinical event should be captured in the source 
documents. Laboratory abnormalities not requiring clinical intervention or further 
investigation will be captured as part of overall laboratory monitoring and should not 
be reported as AEs. 
• A pre-existing condition (eg, allergic rhinitis) must be noted on the appropriate eCRF 
at screening but should not be reported as an AE unless the condition worsens, or 
episodes increase in frequency during the AE reporting period. Diagnostic and 
therapeutic noninvasive and invasive procedures, such as surgery, should not be 
reported as AEs. However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an AE. For example, an 
acute appendicitis that occurs during the study should be reported as the AE and the 
resulting appendectomy should be recorded in the source documents and eCRF. If a 
surgical procedure was planned prior to entry into the study, and the surgery 
performed is not because of a worsening of a baseline condition, this should not be 
reported as an AE. Note that, as described in Section7.5.2.2 any hospitalization 

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occurring as the consequence of an AE during the study period should be reported as 
an SAE. 
Each AE is to be classified as serious or nonserious by the investigator using medical and 
scientific judgment. 
7.5.2.2. 
Definition of Serious Adverse Events 
An SAE is an untoward medical occurrence or effect associated with the use of a gene therapy at 
any dose, regardless of whether it is considered to be related to the gene therapy, which results in 
one of the following: 
• Results in death. This includes all deaths from time of consent until Final Study Visit, 
or within 30 days after Final Study Visit, including deaths due to disease progression. 
Any death occurring later than 30 days following the Final Study Visit need not be 
reported as an SAE unless it is a result of an event that started within the period 
covered by the on-study definition. The reported AE should be the event that caused 
the death. In addition, any AE resulting in death that occurs after the AE reporting 
period and that the investigator assesses as possibly related to the gene therapy should 
also be reported as serious. 
• Is life-threatening. This refers to an event in which the subject was at risk of death at 
the time of the event. It does not include an event that, had it occurred in a more 
severe form, hypothetically might have caused death. 
• Requires hospitalization or prolongation of existing hospitalization (excluding 
hospitalizations for administration of the gene therapy, procedures required by the 
study protocol, or treatment-related diagnostic procedures; other planned 
hospitalizations; or hospitalizations related only to progression of disease). 
Treatments in the emergency room for procedures such as hydration that do not 
require admitting the subject to the hospital and observational durations in the 
emergency room for less than 24 hours do not fall into this category. 
• Results in persistent or significant disability or incapacity or substantial disruption of 
the ability to conduct normal life functions. 
• Any other medically important event that the investigator or the sponsor judges to be 
serious or which is defined as serious by the regulatory agency in the local country. 
These are AEs that might not be immediately life-threatening or result in death or 
hospitalization but might jeopardize the subject or might require intervention to 
prevent one of the other outcomes listed above. Medical judgment should be 
exercised in deciding whether an AE is serious based on above definition. Examples 
of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse. 
• A pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or 
congenital anomaly (including that in an aborted fetus). 
Note that any SAEs occurring within 30 days after the Final Study Visit should be reported to the 
sponsor if the investigator becomes aware of them. 

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7.5.3. 
Adverse Events of Special Interest 
Adverse events of special interest (AESIs) will be captured and monitored during this study. 
Investigators will report all AESIs to PTC Pharmacovigilance, regardless of causality, as 
described in Section 7.5.8. All AESIs should be reported within 24 hours to the PTC 
Therapeutics Pharmacovigilance Department on the SAE form. If the event is considered 
nonserious by the investigator, then the SAE form and AE CRF page should be marked as 
nonserious. 
7.5.3.1. 
Risks of Neurosurgical Procedure 
There are risks associated with neurosurgery, intraputaminal infusion, and use of the cannula, 
including hemorrhage and infection at the infusion site. Adverse events associated with the 
neurosurgical procedure and infusion will be documented and reported as AESIs. 
Surgical AESIs only need to be recorded as such and reported to Pharmacovigilance when 
related to the neurosurgical procedure specifically and not when related to general risks of 
surgery, inclusive of anesthesia-related AEs. 
Adverse events that are nonserious and related to general risks of surgery and anesthesia will be 
recorded as general AEs and will not be reported to PTC Pharmacovigilance. These AEs will be 
captured as described below in Section 7.5.8. 
7.5.3.2. 
Dyskinesia 
Adverse events of dyskinesia have been reported in the clinical studies of eladocagene 
exuparvovec. Dyskinesia may result from the elevated sensitivity of dopaminergic receptors in 
AADC-deficient subjects, which may result from chronic severe deficiency of neurotransmitters. 
After treatment with eladocagene exuparvovec, overstimulation of the dopaminergic receptors 
may manifest as dyskinesia. 
7.5.3.3. 
Cerebrospinal Fluid Leaks 
Cerebrospinal fluid leaks occur when there is a tear or hole in the membranes surrounding the 
brain or spinal cord, allowing the clear fluid that surrounds and cushions those organs to escape. 
Because eladocagene exuparvovec will be administered as an intraputaminal infusion, CSF leaks 
are a potential AE. CSF leaks will be monitored for all subjects intraoperatively and via brain 
MRI with gadolinium upon discharge and at 3 weeks post-surgery. 
7.5.4. 
Adverse Event Recording 
All AEs (both serious and nonserious) that occur in subjects during the AE reporting period 
(screening until the Final Study Visit) must be recorded, whether or not the event is considered 
drug related. 
All AEs are to be recorded in the source documents and on the eCRF using concise medical 
terminology; whenever possible, terms contained in the Medical Dictionary for Regulatory 
Activities (MedDRA) should be employed. In addition, the following information should be 
recorded: 
• Indication of whether the event is serious or nonserious (see Section 7.5.2) 
• Relationship to gene therapy (see Section 7.5.5) 

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• Relationship to surgery 
• Severity of the event (see Section 7.5.6) 
• Onset date 
• Resolution date, or date of death 
• Action taken 
• Outcome of the event 
Classification of the event as serious or nonserious determines the reporting procedures to be 
followed. 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by the 
study subject/parent(s)/legal guardian/legally acceptable representative. In addition, each study 
subject/parent(s)/legal guardian/legally acceptable representative will be questioned about AEs at 
each scheduled clinic visit after gene therapy administration or during any telephone contact with 
the subject/parent(s)/legal guardian/legally acceptable representative. The type of question asked 
should be open-ended, for example, “How have you been feeling?” or a similar type of query. 
7.5.5. 
Describing Adverse Event Relationship to Gene Therapy or Surgery 
The investigator should provide an assessment of the relationship of the AE to the gene therapy, 
the cannula, or the neurosurgery (ie, whether there is a reasonable possibility that the gene 
therapy, the cannula, or the neurosurgery caused the AE) using the considerations outlined in 
Table 4. 
Table 4: 
Relationship of Gene Therapy to Adverse Event 
Relationship 
Description  
Probable  
A clinical event in which a relationship to the gene therapy seems probable because 
of such factors as consistency with known effects of the drug; a clear temporal 
association with the use of the drug; lack of alternative explanations for the event.  
Possible  
A clinical event occurring coincident with administration of the gene therapy and 
which may or may not be explained by concurrent disease or other drugs or 
chemicals.  
Unlikely  
A clinical event with a temporal relationship to the gene therapy exposure that does 
not preclude causality but for which there is a clear alternate cause that is more 
likely to have caused the AE than gene therapy. Such alternatives include a 
concomitantly administered drug, the subject’s disease state, other medical 
conditions, or environmental factors.  
Unrelated  
A clinical event, for which a relationship to the gene therapy seems improbable 
because of factors such as inconsistency with known effects of the gene therapy, 
lack of a temporal association with gene therapy administration, and/or presence of 
alternative explanations for the event. Alternative explanations might include a 
known relationship of the AE to a concomitant drug, medical history of a similar 
event, the subject’s disease state, other medical conditions, or environmental 
factors.  
Abbreviations: AE, adverse event 

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7.5.6. 
Grading of Severity of Adverse Events 
The severity of AE will be graded using the Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0. For each episode, the highest severity grade attained should be reported. 
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: Grade 1 
(mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal) to 
describe the maximum intensity of the AE. For purposes of consistency with the CTCAE, these 
intensity grades are defined in Table 5. 
Table 5: 
Grading of Adverse Event Severity Grade 
Grade 
Adjective 
Description  
1 
Mild 
Sign or symptom is present, but it is easily tolerated, is not expected to 
have a clinically significant effect on the subject’s overall health and 
well-being, does not interfere with the subject’s usual function, and is 
not likely to require medical attention 
2 
Moderate 
Sign or symptom causes interference with usual activity or affects 
clinical status, and may require medical intervention 
3 
Severe 
Sign or symptom is incapacitating or significantly affects clinical status 
and likely requires medical intervention and/or close follow-up  
4 
Life-threatening 
Sign or symptom results in a potential threat to life  
5 
Fatal 
Sign or symptom results in death 
7.5.7. 
Follow-Up of Unresolved Adverse Events 
All AEs should be followed up by the investigator until they are resolved, or the investigator 
assesses them as chronic or stable. The investigator should consider protocol guidelines and use 
his/her discretion in ordering additional tests as necessary to monitor the resolution of such 
events. In the event of additional investigations, the PTC Pharmacovigilance Department or 
designee should be informed via e-mail or fax. A subject withdrawn from the study because of 
an AE must be followed by the investigator until clinical recovery is complete and laboratory 
results have returned to normal, or until progression has been stabilized. Follow-up may need to 
continue after the subject has discontinued from the study, and additional investigations may be 
requested by the medical monitoring team. 
7.5.8. 
Adverse Event Reporting Period 
Investigator site reporting requirements for AEs are summarized in Table 6. 
Table 6: 
Investigator Site Requirements for Reporting Adverse Events 
Event 
Recorded on the eCRF 
Reported to PTC Pharmacovigilance 
Within 24 Hours of Awareness 
Serious AE 
All 
All 
Nonserious AE 
All 
None 
AESIs 
All 
All 
Other, eg, exposure to the 
gene therapy during 
pregnancy or breastfeeding, 
and occupational exposure 
All (regardless of whether 
associated with an AE), 
except occupational 
exposure 
All  
(regardless of whether associated with 
an AE) 
Abbreviations: AE, adverse event; AESI, adverse event of special interest; eCRF, electronic case report form 
The first day of AE reporting will coincide with the date of signing of informed consent and 
including a minimum of 30 calendar days after the Final Study Visit (Month 60), except as 

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described in Section 7.5.4. In addition, SAEs occurring in a subject after the study period should 
be reported to the sponsor if the investigator becomes aware of them. 
The medical monitor will review all AEs and SAEs as they are reported from the site. The 
DSMB will conduct a review of safety data as outlined in the DSMB charter. The DSMB will 
monitor ongoing safety data to ensure subject well-being, safety, and study integrity. 
7.5.9. 
Serious Adverse Event Reporting 
All SAEs should be reported via the SAE report form to PTC within 24 hours of becoming aware 
of the event(s). In addition, the AE portion of the eCRF must also be completed. 
The SAE report form should be signed by the investigator; however, if the investigator is unable 
to sign at the time of the event or within 24 hours, the form should be signed by the clinical staff 
member reporting the SAE (eg, the study coordinator). The SAE report form must be faxed or 
e-mailed to the PTC Pharmacovigilance Department or designee and to the site IRB/IEC 
(if required by local regulations) within 24 hours. 
Follow-up information to the SAE should be clearly documented as “follow-up” in the SAE 
report form and must also be faxed or e-mailed to the same party. All follow-up SAE report 
forms for the event must be signed by the investigator. Any source documents (eg, progress 
notes, nurses’ notes, laboratory and diagnostic test results, discharge summaries) provided to the 
sponsor should be redacted so that the subject’s name, address, and other personal identity 
information are obscured. Only the subject’s study number and initials are to be provided 
(in regions where the provision of such information is permitted). The information in the AE 
portion of the eCRF and the SAE report form(s) must match or be reconciled. Where the same 
data are collected, the forms must be completed in a consistent manner. For example, the same 
AE term should be used on both forms. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (for example, if a subject initially seeks treatment elsewhere), the investigator is to 
report the event within 24 hours after learning of it and to document his/her first awareness of the 
AE. 
The PTC Pharmacovigilance Department contact information for reporting SAEs is provided 
below. This information is also provided in the SAE report form. 
PTC Pharmacovigilance Department 
E-mail: Pharmacovigilance@ptcbio.com 
SAE FAX Line: 1-908-325-0355 
7.5.10. 
PTC Adverse Event Reporting Requirement 
As the sponsor of the study, PTC is responsible for reporting certain safety information, 
particularly SAEs and subject deaths related to participation in the study, to each investigator in 
an expedited manner. If notification of an AE requiring expedited reporting to investigators is 
received, PTC or its designated representative will contact each investigational site participating 
in this study by e-mail, fax, and/or overnight mail such that the investigator can promptly notify 
the site IRB/IEC per their local requirements. The initial expedited safety report will be provided 
as required according to local regulations (eg, within 15 days) after the earliest date PTC or an 

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agent of PTC (eg, a site monitor) becomes aware of an AE. This awareness date is the date the 
regulatory reporting clock begins, and the date is considered Day 0. 
7.5.11. 
Other Safety Assessments 
Other safety assessments will include laboratory assessments (complete blood count with 
differential and platelets, chemistry, and coagulation), physical examinations, vital signs, and 
height and weight. These assessments will be performed as detailed in Table 1,Table 2, and 
Table 3. 
Viral shedding will be assessed in blood, CSF, and urine as per the Schedule of Events to 
identify any possible risk of exposure to those who come into contact with a study subject. 
Anti-AAV2 Antibody testing and T-cell sample collection will be performed as per the Schedule 
of Events to assess the immune response to gene therapy. 
7.5.12. 
Safety Assessment Committee 
The DSMB will evaluate all AEs, SAEs, and AESIs. 

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8. 
STATISTICAL METHODS AND DATA ANALYSIS 
8.1. 
Sample Size Determination 
This study has no formal statistical hypothesis testing, and the sample size is not based on 
statistical consideration. A minimum of 3 subjects is planned to assess HVA level at Week 8 and 
safety of the SmartFlow MR-compatible ventricular cannula for administering eladocagene 
exuparvovec to pediatric subjects. 
8.2. 
Subject Population(s) for Analysis 
The following analysis population will be defined for the study: 
Pharmacodynamic (PD) population: The PD population will consist of all subjects enrolled in the 
study who have received any amount of the study drug and have both baseline and at least one 
post-baseline value of at least one PD variable. 
Safety Population: The safety population will consist of all subjects enrolled in the study who 
have received any amount of study drug. 
Efficacy Population: The efficacy population will consist of all subjects enrolled in the study 
who have received any amount of the study drug and have both baseline and at least one post-
baseline evaluation of at least one efficacy variable. 
All analyses of PD variables will be based on the PD population. Evaluation of the safety 
variables will be based on the safety population, and all efficacy summary and analyses will be 
based on the efficacy population. 
8.3. 
General Approach 
Summaries for PD, safety, and efficacy will be provided from time of gene therapy 
administration until the end of the follow-up. If needed, summaries will be provided for PD, 
safety and, if appropriate, efficacy variables at a timepoint that matches the agreement with the 
health authority. 
Study baseline for a variable is defined as the last non-missing data collected prior to treatment. 
If a separate set of summaries is needed for the Long-Term Extension Phase, baseline for the 
Long-Term Extension Phase is defined as the last non-missing data collected prior to the Long-
Term Extension Phase.  
8.3.1. 
Subject Disposition and Characteristics 
Subject disposition, demographics, and baseline characteristics will be summarized. Reasons for 
study discontinuation and time of withdrawal from study will be described. 
8.3.2. 
Analysis of Primary Endpoints 
8.3.2.1. 
Primary Efficacy Analysis 
Observed values and change from baseline in HVA at Week 8 will be summarized using 
descriptive statistics (count, mean, standard deviation, median, minimum, and maximum) for 
each timepoint. 

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8.3.2.2. 
Primary Safety Analysis 
The primary safety analysis will focus on TEAEs that are defined as AEs with a start date after 
or worsen after receiving eladocagene exuparvovec. 
The time of gene therapy administration will be the start time of the first infusion. All AEs 
reported will be coded using MedDRA. The number and proportion of subjects reporting TEAE 
will be summarized by System Organ Class (SOC) and by Preferred Term (PT) within SOC. 
Summaries will also be provided for each severity grade, relationship to cannula device, to gene 
therapy, and to neurosurgical procedure, and AEs of special interest.  
Serious Adverse Events will be summarized using SOC and PT. 
8.3.3. 
Analysis of Secondary Endpoints 
Observed values and change from baseline in the neurotransmitter CSF metabolites HVA, 5-
HIAA, 3-OMD in CSF; brain 18F-DOPA PET; PDMS-2 total and subscale scores; Bayley-III 
cognitive and total language subscale scores; EQ-5D-Y scores; body weight; and AADC-specific 
symptoms will be summarized using descriptive statistics (count, mean, standard deviation, 
median, minimum, and maximum) or proportion as appropriate for each timepoint. 
The number and percentage of subjects who achieve each motor milestone will be summarized 
by timepoint. 
Oculogyric crisis diary data will be summarized by severity, frequency, and proportion and 
duration of time subjects experienced OGC during the study for selected timepoints, as 
appropriate. 
Respiratory infection rate will be summarized over time. 
TEAEs will be summarized as described in Section 8.3.2. The number of subjects who 
experience dyskinesia, number of dyskinesia episodes, median time to first episode, and 
summary statistics for duration of dyskinesia events will be provided. 
Physical examination, vital signs, MRI, clinical laboratory values, T-cell, anti-AAV2 antibody 
values, and viral shedding will be summarized by visit, and shift table(s) will be provided if 
appropriate. 
8.3.4. 
Planned Interim Analysis 
No interim analysis is planned for this study. 

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9. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
9.1. 
Regulatory, Ethical, and Study Oversight Considerations 
9.1.1. 
Informed Consent Process 
By signing the protocol, the investigator assures that informed consent will be obtained from 
each subject/subject’s caregiver prior to study entry and that the informed consent will be 
obtained in accordance with current regulations. 
The investigator or sub-investigator will give each subject/subject’s caregiver full and adequate 
verbal and written information regarding the objectives and procedures of the study and the 
possible risks involved. An informed consent document will be provided to each 
subject/subject’s caregiver in a language in which they are fluent. This information must be 
provided to the subject/subject’s caregiver prior to undertaking any study-related procedure. 
Adequate time should be provided for the subject/subject’s caregiver to read the informed 
consent, to understand the risks and benefits of participating in the study, and to ask any 
questions that the subject may have about the study. The subject/subject’s caregiver should be 
able to ask additional questions as and when needed during the conduct of the study. The 
subject’s caregivers’ signature on the informed consent form (ICF) should be obtained at the 
investigator site in the presence of the investigator or a qualified representative 
(eg, sub-investigator). 
Each subject/subject’s caregiver will be given a copy of the signed consent form. The original 
signed ICFs will be retained by the investigator with the study records. 
The written subject information must not be changed without prior approval by PTC and the 
IRB/IEC. 
9.1.2. 
Study Discontinuation and Closure 
PTC reserves the right to discontinue the study prior to inclusion of the intended number of 
subjects. The investigator, after consultation with the PTC medical monitor, reserves the right to 
discontinue the study at the investigator site for safety reasons at any time. 
After a decision to terminate the study, investigators must contact all subjects who are continuing 
their participation in the study and must do so within a period set by PTC. As directed by PTC, 
all study materials must be collected, and all electronic data entry forms completed to the 
greatest extent possible. 
9.1.3. 
Confidentiality and Privacy 
Research records will be collected and stored in a manner that protects the confidentiality of 
subject information. The names and identities of all research subjects will be kept in strict 
confidence and will not appear on eCRFs, paper case report forms, or other records provided to 
or retained by PTC (or its authorized designee). The names and identities of the subjects need not 
be divulged; however, the records must nevertheless be inspected. This will be accomplished by 
redacting the subject’s name and replacing the name with the subject’s study identification 
number on any record provided to or retained by PTC. The ICF must include appropriate 
statements explaining these requirements. 

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By signing this protocol, the investigator affirms to PTC that the investigator will maintain, in 
confidence, information furnished by PTC and will divulge such information to the IRB/IEC 
under an appropriate understanding of confidentiality with such board. 
9.1.4. 
Future Use of Stored Specimens and Data 
As part of the current study, biomarker data will be collected from all subjects. 
Processing of genetic, anti-AAV2 antibody, CSF neurotransmitter, and AADC enzyme samples 
will be performed by central laboratories under the direction of the sponsor. Processing, analysis, 
and storage will be performed at a secure laboratory facility to protect the validity of the data and 
maintain subject privacy. 
Samples will only be used for the purposes described in this protocol. Laboratories contracted to 
perform the analysis on behalf of the sponsor will not retain rights to the samples beyond those 
necessary to perform the specified analysis and will not transfer or sell those samples. The 
sponsor will not sell the samples to a third party. 
All samples, with the exception of those collected for anti-AAV2 antibody testing, will be stored 
until the completion of the study (defined as submission of the clinical study report to the 
appropriate regulatory agencies). At the end of the storage period, those samples will be 
destroyed. Samples may be stored longer if a health authority (or medicinal product approval 
agency) has active questions about the study. In this special circumstance, the samples will be 
stored until the questions have been adequately addressed. The samples collected for anti-AAV2 
antibody testing will be stored for potential future testing. No subject-identifying information 
(eg, initials, date of birth, government identifying number) will be associated with any of the 
biologic samples. All samples will be single coded. The sponsor will take steps to ensure that 
data are protected accordingly, and confidentiality is maintained as far as possible. Data from 
subjects enrolled in this study may be analyzed worldwide, regardless of location of collection. 
The sponsor and its representatives and agents may share coded data with persons and 
organizations involved in the conduct or oversight of this research. These include: 
• Contract Research Organizations (CROs) retained by the sponsor 
• IECs or IRBs that have responsibility for this research study 
• National regulatory authorities or equivalent government agencies 
At the end of the analysis, results may be presented in a final report which can include part or all 
the coded data, in listing or summary format. Other publication (eg, in peer-reviewed scientific 
journals) or public presentation of the study results will only include summaries of the 
population in the study, and no identified individual results will be disclosed. 

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9.1.5. 
Safety Oversight 
Safety will be monitored on a regular basis by the sponsor’s medical monitor. To protect 
subjects’ safety, an independent DSMB, which will include a pediatric neurosurgeon and a 
pediatric neurologist, will be established to monitor the ongoing safety data during the Trial 
Phase. Full details of the DSMB procedures, including primary responsibilities of the DSMB, its 
relationship with other study components, its membership, and its purpose and timings of its 
meetings, will be documented in a DSMB charter. These details will also include procedures to 
ensure confidentiality and proper communication, the guidelines to be implemented by the 
DSMB, and an outline of the content of the reports that will be provided to the DSMB. 
The DSMB will conduct a review of safety data as outlined in the DSMB charter. Review 
meetings will allow for the appropriate monitoring of safety related to the surgical procedure 
with the SmartFlow MR-compatible ventricular cannula. Review by DSMB will not be required 
in order to enroll successive subjects. The DSMB will monitor ongoing safety data to ensure 
subject well-being, safety, and study integrity. 
The DSMB may review the safety data at other times as warranted by emerging results. Based on 
review of the safety data, the DSMB can recommend continuation of the study unchanged, study 
interruption, study termination, modification of the trial, or alteration in the DSMB monitoring 
plan. Further information regarding the DSMB review process is provided in the DSMB charter. 
9.1.6. 
Clinical Monitoring 
In accordance with 21 Code of Federal Regulations Part 312.56 and/or relevant ICH guidelines, 
PTC or a designee will periodically inspect all eCRFs, study documents, research facilities, and 
clinical laboratory facilities associated with this study at mutually convenient times, before, 
during, and after completion of the study. As required by applicable regulations (Responsibilities 
of sponsors and investigators), the monitoring visits provide PTC with the opportunity to 
evaluate the progress of the study; verify the accuracy and completeness of data in the eCRFs; 
ensure that all protocol requirements, relevant regulations, and investigator’s obligations are 
being fulfilled; and resolve any inconsistencies in the study records. This includes inspection of 
all documents and records required to be maintained by the investigator, including but not 
limited to medical records (office, clinic, or hospital) for the subjects in this study. The names 
and identities of all research subjects will be kept in strict confidence and will not appear on 
eCRFs or other records retained by PTC. The investigator/institution guarantees direct access to 
source documents by PTC and appropriate regulatory authorities. 
It is important that the investigator and relevant institutional personnel are available during the 
monitoring visits and possible audits or inspections and that enough time is devoted to the 
process. 

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9.1.7. 
Quality Assurance and Quality Control 
To ensure compliance with GCP and all applicable regulatory requirements, PTC, PTC’s 
representatives, a regulatory authority, or an IRB may conduct a quality assurance audit. Reasons 
for quality assurance audit may include but are not limited to random selection, geographic 
proximity, suspected GCP violation, recurring protocol deviations, etc. The purpose of a sponsor 
audit or inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, GCP guidelines of the ICH, and any 
applicable regulatory requirements. The investigator should contact the sponsor immediately if 
contacted by a regulatory agency about an inspection. 
9.1.8. 
Data Handling and Record Keeping 
To enable evaluations and/or audits from regulatory authorities or PTC, the investigator agrees to 
keep accurate and complete records, including the identity of all participating subjects (sufficient 
information to link eCRFs and clinic records/source documents), all original signed ICFs, 
electronic copies (ie, CD-ROM, USB, etc.) or paper copies of the data that have been captured in 
the electronic data capture for each subject (eCRFs), and detailed records of gene therapy 
disposition. All records and documents pertaining to the study will be maintained by the 
investigator until notification is received from PTC that the records no longer need to be 
retained. 
The investigator must obtain written permission from PTC before disposing of any records. The 
investigator will promptly notify PTC in the event of accidental loss or destruction of any study 
records. If the investigator relocates, retires, or for any reason withdraws from the study, the 
study records may be transferred to an acceptable designee, such as another investigator, another 
institution, or to PTC as applicable. 
9.1.9. 
Protocol Deviations 
A protocol deviation is defined as any intentional or unintentional change to, or noncompliance 
with, the approved protocol procedures or requirements. Deviations may result from the action or 
inaction of the subject, investigator, or site staff. Examples of deviations include, but are not 
limited to: 
• Failure to adhere to study exclusion and inclusion criteria 
• Failure to comply with dispensing or dosing requirements 
• Use of medications that are specifically prohibited in the protocol 
• Missed or out-of-window visits 
• Drug dosing not administered within the time frame specified in the protocol 
• Failure to adhere to test requirements, including vital signs, laboratory tests, physical 
examinations, medical history, etc. (either tests not done, incorrect tests done, or not 
done within the time frame specified in the protocol) 
• Procedural deviations such as incorrect storage of gene therapy, failure to update the 
ICF when new risks become known, or failure to obtain IRB approvals for the 
protocol and ICF revisions 

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Major deviations are any deviations that impact subject eligibility (ie, protocol 
inclusion/exclusion violations), subject safety, or a subject’s ability to continue in the clinical 
study. 
At the outset of the study, a process for defining and handling protocol deviations will be 
established with the CRO. This will include determining which deviations will be designated 
major; thus, requiring immediate notification to the PTC medical monitor and the sponsor. 
Prospective deviations (eg, protocol waivers) are prohibited per PTC policy. 
The investigator is responsible for seeing that any known protocol deviations are recorded and 
handled as agreed. 
9.1.10. 
Publication and Data Sharing Policy 
The information developed during the conduct of this clinical study is considered confidential by 
PTC. This information may be disclosed as deemed necessary by PTC. 
PTC intends that the data from this study will be presented and published. The PTC staff in 
collaboration with the investigator will be responsible for writing presentations and manuscripts 
for publication. Investigators will not be allowed to publish or present the data from this study 
without prior agreement with PTC. 
The investigator is obliged to provide the sponsor with complete test results and all data derived 
by the investigator from the study. During the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the Clinical Study Site Agreement, any 
public disclosure (including publicly accessible websites) related to the protocol or study results, 
other than study recruitment materials and/or advertisements, is the sole responsibility of the 
sponsor. 
The sponsor may publish any data and information from the study (including data and 
information generated by the investigator) without the consent of the investigator. Manuscript 
authorship for any peer-reviewed publication will appropriately reflect contributions to the 
production and review of the document. All publications and presentations must be prepared in 
accordance with this section and the Clinical Study Site Agreement. In the event of any 
discrepancy between the protocol and the Clinical Study Site Agreement, the Clinical Study Site 
Agreement will prevail. 
Data from the study will be pooled and analyzed by the sponsor or the sponsor’s designee. If a 
publication is not forthcoming within 12 months of completion of the study, the investigator may 
publish or present the results generated by the study. 
The investigator will provide the sponsor with a copy of any proposed publication or 
presentation for review and comment at least 60 days prior to such presentation or submission 
for publication. The sponsor shall inform the investigator in writing of any changes or deletions 
in such presentation or publication required to protect the sponsor’s confidential and proprietary 
technical information and to address inaccurate data or inappropriate interpretations in the 
context of any pooled multicenter results. At the expiration of such 60-day period, the 
investigator may proceed with the presentation or submission for publication unless the sponsor 
has notified the institution or the investigator in writing that such proposed publication or 
presentation discloses the sponsor’s confidential and proprietary technical information. Further, 

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upon the request of the sponsor, the investigator will delay the publication or presentation for an 
additional 90 days to permit the sponsor to take necessary actions to protect its intellectual 
property interests. 
9.1.11. 
Additional Considerations 
Not applicable. 

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10. 
PROTOCOL AMENDMENT HISTORY 
Version 1.0: 25 February 2020 
Version 1.1: 24 March 2020 
Version 2.0: 17 July 2020 
Version 3.0: 17 August 2020 
Version 4.0: 24 November 2020 
Version 5.0: 21 April 2021 
Version 6.0: 16 August 2021 
Version 7.0: 11 November 2021 
Version 8.0: 22 March 2022 
Version 9.0: 20 July 2022 
Version 10.0: 28 April 2023 
Version 11.0: 01 September 2023 
10.1. 
Version 1.1: 24 March 2020 
Overall reason for Version 1.1: The overall reason for this amendment was to incorporate 
feedback from FDA. 
Item 
No. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version and abbreviations were updated; small 
grammatical and format changes were made throughout. Added 
pediatric to characterize study population. 
Update 
2 
Synopsis, 
2.3.2, 7.4, 
8.3.4 
Changed section to Exploratory Endpoints, and deleted AIMS, 
Bayley Scale of Infant Development, Gross Motor Function 
Measure, and Manual Ability Classification System. 
Agency 
request 
3 
3.1 
Added an interval of 3 weeks between successive subjects. 
Agency 
request 
4 
Synopsis, 
3.1, 7.1 
Changed Part A and Part B to Trial Phase and Extension Phase. 
Update 
5 
Synopsis, 
4.1 
Deleted former Inclusion Criterion 2, added new inclusion criteria for 
age, cranium development, lack of benefit from standard medical 
therapy, unable to ambulate independently, and laboratory values 
within normal pediatric range. 
Agency 
request 
6 
5.3 
Allow treatments for AADC deficiency throughout study duration as 
long as prespecified conditions are met. 
Agency 
request 
7 
6.1 
Added stopping rules. 
Agency 
request 
8 
7.1 
• Clarified hospitalization stay. 
• Specified that PDMS-2 should be done at same time of day at 
baseline, 6 months, 12 months. 
• Deleted AIMS, Bayley Scale of Infant Development, Gross Motor 
Function Measure, and Manual Ability Classification System. 
Agency 
request 
9 
7.5.1 
Added peri-operative safety monitoring measures. 
Agency 
request 

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Item 
No. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
10 
7.5.2.2 
Deleted sentence that an event need not be reported as an SAE if it 
exclusively represents a relapse of an expected change or 
progression. 
Agency 
request 
11 
7.5.12 
Added an independent pediatric neurologist to evaluate safety. 
Agency 
request 
12 
Attachment 
1 
Added PDMS-2 score sheet. 
Agency 
request 
10.2. 
Version 2.0: 17 July 2020 
Overall reason for Version 2: The overall reason for this amendment was to address feedback 
from FDA. 
Item 
No. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version and abbreviations were updated; minor 
grammatical, format changes, and clarifications were made 
throughout. 
The Study Visits were changed from months to weeks. 
The Summary of Events was split into 2 tables and the other 
tables in the document were renumbered. 
The visits/assessments in the new Summary of Events table 
reporting the Extension Phase (the new Table 2) were revised to 
streamline the in-clinic visits. 
Update 
2 
Synopsis 
For clarity, text was added regarding the number of subjects to be 
enrolled. 
Details pertaining to DSMB safety monitoring were added. 
Inclusion criteria #1 and #2 and exclusion criteria #5 were 
modified for clarity. 
Text regarding metal was added to exclusion criteria #3. 
Inclusion and Exclusion Criteria were added to explain criteria 
regarding pregnancy and breastfeeding. 
Brain 18F-DOPA PET was added as an Other Exploratory 
Endpoint. 
Update 
3 
Protocol 
Identifiers 
and Study 
Personnel 
The “P” from the IND number was deleted as it is not applicable. 
Update 
3 
2.3.2, 
8.3.4 
Brain 18F-DOPA PET was added as an Other Exploratory 
Endpoint. 
Update 
4 
3.1, 8.1 
For clarity, text was added regarding the number of subjects to be 
enrolled. 
Update 
5 
3.1 
Details pertaining to DSMB safety monitoring were added. 
The length of the study was changed from “13 months” to 
“54 weeks”. 
Update 
6 
3.2 
Text regarding the relative average mass of a child brain versus 
the adult brain has been deleted. 
Text regarding infusion was modified to be consistent with the 
Surgical Manual. 
Update 
7 
4.1 
Inclusion criteria #1 and #2 were modified for clarity. 
Inclusion criteria were added to explain criteria regarding 
pregnancy. 
Update 

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Item 
No. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
8 
4.2 
Text regarding metal was added to exclusion criteria #3. 
Exclusion criteria #5 was modified for clarity. 
Exclusion criteria was added to explain criteria regarding 
pregnancy and breastfeeding. 
Update 
9 
5.1 
Text regarding infusion was modified to be consistent with the 
Surgical Manual. 
Update 
10 
5.2.2 
IP storage conditions revised from “-80°C” to “≤-65°C.” 
Update 
11 
5.3 
For clarity, “dosage has been stable for a minimum of 6 months” 
has been deleted from the list of requirements for the medications 
related to the treatment of AADC deficiency. 
Update 
12 
6.1 
Stopping rules were updated. 
Agency 
request 
13 
6.2 
Text regarding withdrawal of consent was modified for clarity. 
Update  
14 
7.1 
The study days for screening was changed. 
Brain MRI with gadolinium to assess for CSF leakage/fistula or 
signs of inflammation was added upon discharge and at 3 weeks 
post-surgery. 
Collecting CSF history and genetic testing were added as 
assessments. 
Visits were modified for CSF neurotransmitter analysis, Brain 
MRI, Brain CT, 24-hour Holter Monitor, laboratory tests, and 
PDMS-2. 
Definitions for a complete physical and targeted physical 
examinations were added. 
Text added to the MRI sequencing as clarification. 
Phone visits were added for AE assessments. 
Text to state “with gadolinium” was added to footnotes regarding 
MRIs. 
Footnotes regarding analysis by a central lab and admitting 
subjects to the hospital at the discretion of the PI were added. 
Update and 
Agency 
request 
15 
7.3 
Text stating that PET imaging will be analyzed by a central reader 
was added. 
Update 
16 
7.4.4 
Details regarding untreated CSF samples and metabolites was 
deleted since the details are not needed for a protocol. 
Update 
17 
7.5.1 
Text was added to clarify wound closure techniques. 
Text regarding assessing complications, if needed, was modified. 
Agency 
request/Update 
18 
7.5.3.3 
Brain MRI with gadolinium to assess for CSF leakage/fistula or 
signs of inflammation was added upon discharge and at 3 weeks 
post-surgery. 
Agency 
request 
19 
7.5.5 
Text regarding withdrawal and rechallenge of study drug was 
deleted from Table 2 since this is a single-dose study. 
Update 
20 
7.5.8 
AEs of Special Interest were added to Table 4. 
Update 
21 
7.5.8, 
7.5.12, 
9.1.5 
Details pertaining to DSMB safety monitoring were added. 
Agency 
request 
22 
9.1.4 
For clarity, text regarding processing samples and storage was 
modified. 
Paragraph regarding biomarker analysis was deleted as this is no 
longer applicable to this study. 
Update 
23 
9.1.9, 
9.1.10 
Text updated to current PTC terminology. 
Update 

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10.3. 
Version 3.0: 17 August 2020 
Overall reason for Version 3.0: To update the protocol based on the assessments and analysis 
that will conducted during the study. 
Item 
No. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version and abbreviations were updated; minor 
grammatical, format changes, and clarifications were made 
throughout.  
Update 
2 
Synopsis 
The Inclusion criteria was modified to clarify the genetic testing and 
enzyme activity is required. Also, the Inclusion criteria was modified 
to take out the CSF history as it will not be required for inclusion. 
The Statistical Methods section was updated for clarity and to add 
text regarding the analysis for the Extension Phase. 
Update 
3 
2.3.1 
Corrected “54 weeks” to “48 weeks”. 
“24-hour Holter Monitor” will not be assessed. Therefore, the 
assessment has been deleted from the protocol. 
Update 
4 
4.1 
The Inclusion criteria was modified to clarify the genetic testing and 
enzyme activity is required. Also, the Inclusion criteria was modified 
to take out the CSF history as it will not be required for inclusion. 
Update 
5 
7.1 
(Schedule 
of Events 
for the Trial 
Phase and 
the 
Extension 
Phase) 
Rows to report the type of visit were added. 
Viral Shedding was added as an assessment. 
The rows reporting the eDiary for Oculogyric crisis were modified. 
“24-hour Holter Monitor” will not be assessed. Therefore, the 
assessment has been deleted from the protocol. 
Oculogyric crisis removed from Table 2 (the Extension Phase 
table). 
Dosing Day (D1) was added as a visit for “Brain MRI (T1-MPRAGE 
and T2-FLAIR sequences).” 
A row for “Real-time intrasurgical MRI” was added. 
Pregnancy Serum βHCG Test was added as an assessment during 
the Extension Phase. 
The rows for “AEs” and “AE phone visit” were combined into one 
row. 
Footnotes were updated for clarity, based on what will be 
assessed, and/or for consistency with the changes made to the 
tables. 
Update 
6 
7.4.3 
Text regarding the eDiary was added for clarity. 
Update 
7 
7.5.11 
“24-hour Holter Monitor” will not be assessed. Therefore, the 
assessment has been deleted from the protocol. 
Viral Shedding was added as an assessment. 
Update 
8 
8.1 
The statement regarding sample size was replaced with “This study 
has no formal statistical hypothesis testing.” 
Update 
9 
8.3 
Text was added to clarify the baseline definition for a variable. 
Update 
10 
8.3.1 
Statement regarding subject characteristics at study entry was 
deleted. 
Update 
11 
8.3.2 
Definition of when a TEAE should be recorded was clarified. 
Update 
12 
8.3.4 
Text was added to describe the analysis for OGC data. 
Update 
13 
9.1.5 
Text regarding the timing for the DSMB monitoring were added. 
Update 

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10.4. 
Version 4.0: 24 November 2020 
Overall reason for Version 4.0: To update study assessments and revise the Schedule of Events. 
Item 
No. 
Protocol Section Amendment/Update 
Reason/ 
Rationale 
1 
Protocol 
Document date/version and abbreviations were updated; minor 
grammatical, format changes, and clarifications were made 
throughout.  
Update 
2 
5.3 
Language prohibiting the use of blood thinners 7 days prior to 
surgery was added. 
Update 
3 
7.1 (Schedule of 
Events) 
The visit windows for the Screening Visit and Baseline Visit 
were updated to Week -6 to Week -2 and ±3 days, respectively. 
Update 
4 
7.1 (Schedule of 
Events) 
Footnotes in the Schedule of Events were revised and updated. 
Update 
5 
7.1 (Schedule of 
Events for the 
Trial Phase) 
5-HTP was added to footnote e. 
Update 
6 
7.1 (Schedule of 
Events for the 
Trial Phase) 
Footnote “h” describing collection of CSF for analysis of viral 
shedding during the surgical procedure was added. 
Update 
7 
7.1 (Schedule of 
Events for the 
Trial Phase) 
The predose brain CT scan was removed. 
Update 
 
7.1 (Schedule of 
Events for the 
Trial Phase) 
Laboratory tests were added to the Screening Visit in the 
Schedule of Events for the Trial Phase. 
Update 
8 
7.5 
Language describing a home care services option was added. 
Update 
10.5. 
Version 5.0: 21 April 2021 
Overall reason for Version 5.0: To revise the timing of DSMB review of subject safety data. 
Protocol Section 
Amendment/Update 
Reason/Rationale 
Protocol 
Document date/version and abbreviations were updated; 
minor grammatical changes, format changes, and 
clarifications were made throughout.  
Update. 
Protocol 
Identifiers and 
Study Personnel 
Study personnel were updated. 
Update. 
Synopsis, 
Section 3.1, 
Section 7.5.8, 
Section 9.1.5 
The time period for DSMB review of subject safety data was 
updated to 3 weeks after the first and third subjects are 
dosed, and 3 weeks after every third subject is dosed, 
thereafter. Additionally, language describing the formal 
review of AE data to the DSMB was updated to 2 weeks after 
the first subject is dosed.  
Update. 
Synopsis, 
Section 3.1, 
Section 7.5.8, 
Section 9.1.5 
A statement to clarify that DSMB review is not required to 
enroll successive subjects was added. 
Update. 

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Protocol Section 
Amendment/Update 
Reason/Rationale 
Synopsis, 
Section 3.1 
The interval of at least 4 weeks between dosing subjects was 
removed. 
The removal of 
mandatory wait 
time between 
subjects is 
supported by the 
safety of drug 
product, as 
demonstrated by 
the 28 subjects 
treated in the 
eladocagene 
exuparvovec trials 
conducted in 
Taiwan, and the 
safety of the drug 
product and the 
SmartFlow 
cannula, as 
demonstrated by 
2 subjects in the 
French Temporary 
Use Authorization 
(ATU) study.  
Section 3.1 
Information about the option for subjects to roll into a 
long-term follow-up study was added. 
Update. 
Synopsis, 
Section 3.1 
Revised Inclusion Criterion 1 to include subjects with 
“genetically confirmed AADC deficiency with typical clinical 
characteristics” and deleted “confirmed diagnosis of AADC 
deficiency confirmed by compound heterozygous or 
homozygous pathogenic variants in the DDC gene.” 
Update. 
Section 4.1, 
Section 7.1  
An inclusion criterion stating that subjects must test negative 
for COVID-19 a maximum of 72 hours prior to gene therapy 
administration was added. If a subject tests positive for 
COVID-19 at the Screening or Baseline Visit, he/she will 
need to have negative test results for 2 weeks (2 weeks 
since the last positive test result and 2 negative test results a 
minimum of 14 days apart, with the second negative test 
result no more than 72 hours prior to surgery) before 
receiving gene therapy. This requirement was included in the 
Letter of Clarification #3, dated 11 January 2021, and the 
criterion added to the protocol covers all requirements stated 
in the Letter of Clarification (ie, that a subject tests negative 
prior to receiving gene therapy). 
Update. 
Section 4.3  
Rescreening language was revised to include subjects who 
test positive for COVID-19. 
Update. 
Section 5.4 
Language describing the permissibility of COVID-19 vaccines 
as concomitant therapy was added. 
Update. 
Section 5.5 
A new section, Organ Donation, was added to provide 
guidance about donation of organs, tissues, blood, and body 
fluids during and after the study. 
Update. 
Section 6.1 
The occurrence of any significant procedural deviation or 
violations (eg, dosing error or equipment failure) was 
removed from the list of events that would lead to halting of 
study enrollment. 
Update. 

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Protocol Section 
Amendment/Update 
Reason/Rationale 
Section 7.1 
The baseline MRI assessment (T1-MPRAGE and T2-FLAIR 
sequences) was removed from the Schedule of Events for 
the Trial Phase. 
The assessment 
was removed to 
streamline and 
simplify the 
Screening and 
Baseline Visits, 
and to limit the 
subjects’ 
exposure to 
sedation. 
Section 7.1 
A footnote was added to describe flexibility around the 
Screening Visit window if there are unforeseen 
circumstances that impact the subject’s ability to adhere to 
the window. 
Update. 
Section 7.1 
COVID-19 testing was added to the Baseline Visit. A footnote 
explaining that the subject must test negative for COVID-19 a 
maximum of 72 hours before receiving gene therapy was 
added. If a subject tests positive for COVID-19 at the 
Screening or Baseline Visit, he/she will need to have 
negative test results for 2 weeks (2 weeks since the last 
positive test result and 2 negative test results a minimum of 
14 days apart, with the second negative test result no more 
than 72 hours prior to surgery) before receiving gene 
therapy. 
Update. 
Section 7.1 
Pregnancy testing was added to Dosing Day (D1) and 
removed from Discharge Day (Day 3). 
Update. 
Section 7.1 
βHCG was removed from the required pregnancy test. 
Update. 
Section 7.1 
Pregnancy testing was added to the Week 12 and Week 36 
visits. 
Update. 
Section 7.1 
Lumbar puncture was added to footnote n in Table 1 and 
footnote g in Table 2.  
Update. 
Section 7.1 
Footnote r for Table 1 was updated to include “for each OGC 
occurrence”. 
Update. 
10.6. 
Version 6.0: 16 August 2021 
Overall reason for Version 6.0: To update the study stopping rules and Schedule of Events. 
Protocol 
Section 
Amendment/Update 
Reason/Rationale 
Protocol 
Document date/version and abbreviations were updated; minor 
grammatical changes, format changes, and clarifications were 
made throughout.  
Update. 
Section 1.2  
 
Information for the ongoing clinical Studies AADC-010 and 
AADC-011 was updated. 
Update. 
Synopsis, 
Section 2  
 
Language describing the primary objective was revised for 
clarity. No change to the primary objective was made. 
Update. 
Synopsis, 
Section 2  
The Bayley-III and EQ-5D-5L were added as other exploratory 
endpoints. 
Update. 
Synopsis, 
Section 3.1, 
Section 7.5.8, 
Section 9.1.5  
The timing of DSMB reviews was revised to at least 3 weeks 
after the first subject is dosed, at least 3 weeks after the third 
subject is dosed, and at least 3 weeks after every third subject 
thereafter is dosed. 
Update. 

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Protocol 
Section 
Amendment/Update 
Reason/Rationale 
Section 3.1, 
Section 7.1  
The Screening Window was extended from -6 to -2 weeks prior 
to dosing to -10 to -2 weeks prior to dosing. The total length of 
study, including the Screening Window, is now 58 weeks. The 
footnote describing the Screening Window was updated. 
Update. 
Section 3.1  
Details pertaining to the length of the long-term follow-up study 
were updated. 
Update. 
Section 6.1  
The subject-level and study-level stopping rules were updated 
to include presence of a clinically significant CSF leak, in the 
opinion of the investigator. 
Update. 
Section 7.1 
A COVID-19 test was added to the Schedule of Events for the 
Trial Phase at Dosing Day. 
Update. 
Section 7.1 
A footnote clarifying that P-A and lateral chest x-rays will be 
performed was added. 
Update. 
Section 7.1 
Text clarifying that the CMP portion of the laboratory test will 
include total bilirubin was added to the Schedule of Events for 
the Trial Phase and the Extension Phase. 
Update. 
Section 7.1, 
Section 7.5.1.1  
T-cell sample collection was added to the Schedule of Events 
at Screening, Dosing Day, Visit 4, Visit 6, Visit 9, Visit 11, Visit 
14, Visit 17, and Visit 20. 
Update. 
Section 7.1 
Details pertaining to collection of urine for viral shedding 
assessments were added in a footnote to the Schedule of 
Events for the Trial Phase and the Extension Phase. 
Update. 
Section 7.1 
Activated partial thromboplastin time (aPTT) was added to the 
list of coagulation tests in the laboratory tests in the Schedule 
of Events for the Trial Phase and the Extension Phase. 
Update. 
Section 7.1, 
Section 7.3  
A statement about Bioclinica performing central reads on PET 
scans was added. 
Update. 
Section 7.1, 
Section 7.3.3  
The Bayley-III assessment was added to the Schedule of 
Events at Baseline, Visit 14, and Visit 20, and a description of 
the assessment was added. 
Update. 
Section 7.1, 
Section 7.3.4  
The EQ-5D-5L was added to the Schedule of Events at 
Baseline, Visit 14, and Visit 20, and a description of the 
assessment was added.  
Update. 
Section 7.5.3.1  Language related to reporting AESIs related to the 
neurosurgical procedure to PTC Pharmacovigilance was 
revised to capture events specific to the neurosurgical 
procedure and not general risks associated with surgery. Other 
AEs that may occur during the surgical procedure will be 
captured as general AEs as described in Section 7.6.8. 
This language was 
updated to ensure 
that risks 
associated 
specifically with the 
neurosurgical 
procedure are 
reported to PTC 
Pharmacovigilance. 
Section 8.3  
The General Approach section of the Statistical Methods and 
Data Analysis was updated to reflect changes to study 
assessments (Bayley-III, EQ-5D-5L, and body weight) in this 
amendment. Other revisions were made for clarity. 
Update. 

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10.7. 
Version 7.0: 11 November 2021 
Overall reason for Version7.0: To update the protocol to align with administrative letters and 
assessment updates. 
Protocol 
Section 
Amendment/Update 
Reason/ 
Rationale 
Protocol 
Document date/version were updated, and minor 
typographical/formatting changes were made. 
Update. 
Synopsis 
The length of time for the long-term follow-up study was updated to 10 
years for consistency with the rest of the document. 
Update. 
Synopsis, 
Section 2.3.2, 
Section 7.1, 
Section 7.3.4, 
Section 8.3.4  
The EQ-5D-5L assessment was changed to the EQ-5D-Y assessment 
for subjects in the study. 
Update. 
Synopsis, 
Section 3.1, 
Section 7.5.8, 
Section 9.1.5 
The language describing the timing of DSMB reviews and general 
information about DSMB reviews was revised. 
Update. 
Section 1.2 
Description of completed clinical Study AADC-010 was updated. 
Update. 
Synopsis, 
Section 4.1  
The new inclusion criterion #8 was added: Subject must be on stable 
dosage for 3 months prior to baseline for all medications related to 
treatment of AADC deficiency, including dopamine agonists, monoamine 
oxidase inhibitors, anticholinergic drugs, and vitamin B6. 
Update. 
Section 5.3.4  
The formulation, appearance, packaging, and labeling section was 
updated to align with the most recent IB and Chemistry, Manufacturing 
and Controls module documents. 
Update. 
Section 6.1  
Language to include applicable country health authorities was added. 
Update. 
Section 7.1  
Footnote a in the Schedule of Events for the Trial Phase was updated to 
include which Screening assessments (local laboratory assessments, 
physical examination, and vital signs) need to be repeated if the Baseline 
Visit does not occur within 9 weeks after the Screening Visit per the 
Screening Window. 
Update. 
Section 7.1  
Footnote c in the Schedule of Events for the Trial Phase were revised for 
clarity. 
Update. 
Section 7.1  
Footnote d in the Schedule of Events for the Trial Phase was added to 
provide exemption from genetic testing in cases where subjects have 
available genetic enzyme testing results. 
Update. 
Section 7.1, 
Section 7.3.6 
Language describing the OGC eDiary was revised and updated to 
describe both an eDiary and a paper diary and to include that in the 
event that the eDiary cannot be used, a paper diary will be provided. 
Update. 
Section 7.3.2 
A description of the motor achievement for a score of 1 for each of the 
motor milestones was added. 
The language describing the scores of “1” and “2” for PDMS-2 skill items 
was revised such that scores of “1” are defined as achieving an 
emerging skill and scores of “2” are defined as mastery of the skill to 
align with how PDMS-2 subject data are analyzed. 
Update. 
Section 7.5.3, 
Section 7.5.3.1 
Instructions for reporting AESIs using the SAE form and clarification 
about reporting AESIs related specifically to the neurosurgical procedure 
were added. 
Update. 

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10.8. 
Version 8.0: 22 March 2022 
Overall reason for Version 8.0: To add the optional Long-Term Extension Phase of the study to 
the protocol and to update to align with procedural clarifications. 
Protocol Section 
Amendment/Update 
Reason/ Rationale 
Protocol 
The version number and date were updated throughout. 
Editorial and administrative revisions (eg, typographical 
error, punctuation, tenses, abbreviations) were incorporated 
to provide clarity. The synopsis and Schedule of Events 
were updated to be consistent with changes in the protocol. 
Update. 
Protocol 
Identifiers and 
Study Personnel 
Study personnel were updated. 
Update. 
Section 1.2  
The duration of Study 011 was updated to 13 months.  
Update. 
Section 3.1, 
Section 3.3  
The protocol was amended to include an optional 
Long-Term Extension Phase in order to capture long-term 
safety and efficacy data for subjects treated in the Trial 
Phase and Extension Phase.  
Update. 
Section 4.1  
Inclusion criterion 11 was updated for consistency with 
inclusion criterion 12. The words “with custody” were added 
to the criterion. 
Update. 
Section 4.3 
Language related to rescreening for subjects who withdraw 
consent prior to dosing was added. 
Update. 
Section 7.1  
Footnote a was added to the Schedule of Events for all 
Phases to allow flexibility for timing of study visits. 
Update. 
Section 7.1  
A footnote was added to the to the Schedule of Events for 
all phases of the study to specify the age requirement for 
administering the EQ-5D-Y. 
Update. 
Section 7.1  
Text was added to the footnote pertaining to COVID-19 
testing in the Schedule of Events for the Trial Phase. The 
requirement for pre-consent and a negative test prior to the 
Screening Visit was added. 
Update. 
Section 7.1, 
Section 7.3  
The vendor name (Bioclinica) was removed from the PET 
footnotes in the Schedule of Events for the Trial Phase and 
Extension Phase and from the description of the PET scans 
in Section 7.3. 
Update. 
Section 7.1 
Footnote l was deleted for the CSF neurotransmitter and 
viral shedding (CSF) assessment on the day of surgery in 
the Schedule of Events for the Trial Phase as the timing of 
the assessment is captured in footnote m. 
Clarification. 
Section 8  
The Statistical Methods and Data Analysis Section was 
updated to include information about the optional Long-
Term Extension Phase.  
Edits were also made for clarity in General Approach, and 
Analysis of Safety Endpoints. 
Update. 

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10.9. 
Version 9.0: 20 July 2022 
Overall reason for Version 9.0: To update the protocol to align with administrative letters and 
procedural updates. 
Protocol Section 
Amendment/Update 
Reason/ Rationale 
Protocol 
The version number and date were updated throughout.  
Update. 
Section 7.1  
Footnote o in Table 1 and footnote i in Table 2 were 
updated in the Schedule of Events to allow for an additional 
day of flexibility for timing of study visits and to add clinical 
assessment details. 
Update. 
Section 7.3  
Language regarding the PET tracer dose was updated to 
align with the PET Imaging manual instructions. Edits 
resulted in the removal of references.  
Update. 
Section 11  
Removed references related to the updated paragraph in 
Section 7.3 as those citations are no longer relevant. 
Update. 
10.10. 
Version 10.0: 28 April 2023 
Overall reason for Version 10.0: To reposition the assessment of HVA levels as a primary 
endpoint. 
Protocol Section 
Amendment/Update 
Reason/ Rationale 
Protocol 
The version number and date were updated throughout. 
Editorial and administrative revisions (eg, typographical 
error, punctuation, tenses, abbreviations) were incorporated 
to provide clarity. The synopsis was updated to be 
consistent with changes in the protocol. 
Update 
Section 1.1.1  
The current treatments for AADC deficiency were updated 
to reflect that eladocagene exuparvovec has approval in the 
European Union and United Kingdom. 
Update 
Section 1.2  
The status of ongoing and completed studies was updated.  
Update 
Section 1.3  
The rationale for using HVA level as an endpoint was 
added. 
Update  
Section 1.4  
Evaluation of HVA levels was added as a purpose of this 
study.  
Update  
Section 2, 
Section 3.1, 
Section 7.2, 
Section 7.3, and 
Section 8  
The objectives and endpoints were amended so that HVA 
level at Week 8 is a primary endpoint, and all previous 
exploratory endpoints are now secondary endpoints.  
Update  
Table 3  
The window for the final visit (Week 96) was extended to 2 
weeks following feedback on practicability.  
Update  
Section 7.5.5  
Clarification was added that adverse events can be 
attributed to either the gene therapy, the cannula, or 
surgery. 
Clarification 

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10.11. 
Version 11.0: 01 September 2023 
Overall reason for Version 11.0: To extend the study duration to a total of 60 months (5 years). 
Protocol Section 
Amendment/Update 
Reason/ 
Rationale 
Protocol 
The version number and date were updated throughout. 
Editorial and administrative revisions (eg, typographical 
error, punctuation, tenses, abbreviations) were 
incorporated to provide clarity. The objectives and 
endpoints were amended to reflect the change in the 
length of the study.The study length was revised to 5 
years (60 months) and the word “optional” was removed 
from the description of the Long-Term Extension Study. 
The synopsis was updated to be consistent with changes 
in the protocol. 
Update to reflect 
change in study 
length.  
Section 1.2  
Details pertaining to the ongoing Study 1602 were 
updated to reflect the most recent data.  
Update 
Section 2.2, 3.3 
and 7.5.8  
Added long-term efficacy through Month 60 to the 
description of secondary endpoints. 
Update  
Section 7.1, Table 3  
Additional phone and in-person visits were added to 
reflect the extension of the total length of the study to 5 
years (60 months) and capture the assessments that will 
be performed during those visits.  
Update  

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11. 
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APPENDIX 1. 
PDMS-2 SCORE SHEET 

Signature Page for Global PTC-AADC-GT-002 Clinical Protocol V11.0 - 01SEP2023 v1
Signature Page for VV-CLIN-003803 v16.0
Clinical Approval
I approve the document(s)
03-Sep-2023 13:43:53 GMT+0000
Clinical Approval
I approve the document(s)
04-Sep-2023 09:49:42 GMT+0000
Statistics Approval
I approve the document(s)
05-Sep-2023 12:08:55 GMT+0000