Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
Phase: PHASE3
Conditions: Spinal Muscular Atrophy
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
OAV101 
Clinical Trial Protocol COAV101B12302 / NCT05386680
Phase IIIb, open-label, single-arm, multi-center study to 
evaluate the safety, tolerability and efficacy of OAV101 
administered intrathecally (1.2 x 1014 vector genomes) to 
participants 2 to < 18 years of age with spinal muscular 
atrophy (SMA) who have discontinued treatment with 
nusinersen (Spinraza®) or risdiplam (Evrysdi®) 
Document type: 
Clinical Trial Protocol (Clean) 
EUDRACT number: 
2021-006709-31 
Version number: 
01 (Amended Protocol) 
Clinical Trial Phase: 
IIIb 
Release date: 
17-May-2023 (content final)
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 4.0 dated 15-Feb-2021 

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 6 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ............................................................................................................... 11 
Amendment 1 (17-May-2023) ........................................................................................... 14 
Protocol summary .............................................................................................................. 18 
1 
Introduction ....................................................................................................................... 23 
1.1 
Background ............................................................................................................ 23 
1.2 
Purpose .................................................................................................................. 26 
2 
Objectives, endpoints and estimands ................................................................................. 26 
2.1 
Primary estimands ................................................................................................. 28 
2.2 
Secondary estimands ............................................................................................. 29 
3 
Study design ...................................................................................................................... 29 
4 
Rationale ............................................................................................................................ 30 
4.1 
Rationale for study design ..................................................................................... 30 
4.1.1 
Rationale for choice of background therapy ......................................... 31 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 31 
4.3 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ...................................................................................................................... 32 
4.4 
Purpose and timing of interim analyses/design adaptations .................................. 32 
4.5 
Risks and benefits .................................................................................................. 32 
4.6 
Rationale for Public Health Emergency mitigation procedures ............................ 34 
5 
Study Population ............................................................................................................... 34 
5.1 
Inclusion criteria .................................................................................................... 34 
5.2 
Exclusion criteria ................................................................................................... 35 
6 
Treatment ........................................................................................................................... 37 
6.1 
Study treatment ...................................................................................................... 37 
6.1.1 
Investigational and control drugs .......................................................... 37 
6.1.2 
Additional study treatments .................................................................. 38 
6.1.3 
Treatment arms/group ........................................................................... 38 
6.1.4 
Treatment duration ................................................................................ 38 
6.2 
Other treatment(s) .................................................................................................. 38 
6.2.1 
Concomitant therapy ............................................................................. 39 
6.2.2 
Prohibited medication ........................................................................... 39 

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6.3 
Preparation and dispensation ................................................................................. 40 
6.3.1 
Handling of study treatment and other treatment .................................. 41 
6.4 
Participant numbering, treatment assignment, randomization .............................. 41 
6.4.1 
Participant numbering ........................................................................... 41 
6.4.2 
Treatment assignment, randomization .................................................. 42 
6.5 
Treatment blinding ................................................................................................ 42 
6.6 
Dose escalation and dose modification.................................................................. 42 
6.6.1 
Definitions of dose limiting toxicities (DLTs) ...................................... 42 
6.6.2 
Dose modifications ................................................................................ 42 
6.6.3 
Follow-up for toxicities ......................................................................... 42 
6.7 
Additional treatment guidance ............................................................................... 43 
6.7.1 
Treatment compliance ........................................................................... 43 
6.7.2 
Administration procedures .................................................................... 43 
6.7.3 
Post-administration monitoring ............................................................. 43 
6.7.4 
Recommended treatment of adverse events .......................................... 43 
6.7.5 
Emergency breaking of assigned treatment code .................................. 43 
7 
Informed consent procedures ............................................................................................ 43 
8 
Visit schedule and assessments ......................................................................................... 46 
8.1 
Screening ............................................................................................................... 54 
8.1.1 
Inclusion and exclusion criteria ............................................................ 54 
8.1.2 
Information to be collected on screening failures ................................. 54 
8.1.3 
Prior medications .................................................................................. 55 
8.1.4 
Medical history and current medical conditions ................................... 55 
8.1.5 
Screening laboratory tests ..................................................................... 55 
8.1.6 
Virus serology ....................................................................................... 55 
8.1.7 
Ventilatory support................................................................................ 56 
8.1.8 
Radiological evaluations ....................................................................... 56 
8.2 
Participant demographics/other baseline characteristics ....................................... 56 
8.3 
Efficacy .................................................................................................................. 57 
8.3.1 
Secondary efficacy assessments ............................................................ 57 
8.3.2 
Appropriateness of efficacy assessments .............................................. 58 
 
 58 
8.4 
Safety ..................................................................................................................... 62 
8.4.1 
Laboratory evaluations .......................................................................... 62 
8.4.2 
Cardiac evaluations ............................................................................... 65 

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8.4.3 
Pregnancy testing .................................................................................. 66 
8.4.4 
Suicidal ideation and behavior assessment ........................................... 67 
8.4.5 
Clinical safety evaluations .................................................................... 68 
8.4.6 
Anthropometry ...................................................................................... 70 
8.4.7 
Appropriateness of safety measurements .............................................. 71 
8.5 
Additional assessments .......................................................................................... 71 
8.5.1 
Clinical Outcome Assessments (COAs) ............................................... 71 
 
 72 
 
 73 
 
 74 
9 
Discontinuation and completion ........................................................................................ 74 
9.1 
Discontinuation from study treatment and from study .......................................... 74 
9.1.1 
Discontinuation from study treatment ................................................... 74 
9.1.2 
Discontinuation from study ................................................................... 75 
9.1.3 
Lost to follow-up ................................................................................... 75 
9.2 
Withdrawal of informed consent/Opposition to use data/biological samples ....... 75 
9.3 
Study completion and post-study treatment .......................................................... 76 
9.4 
Early study termination by the sponsor ................................................................. 76 
10 Safety monitoring, reporting and committees ................................................................... 77 
10.1 
Definition of adverse events and reporting requirements ...................................... 77 
10.1.1 
Adverse events ...................................................................................... 77 
10.1.2 
Serious adverse events .......................................................................... 78 
10.1.3 
SAE reporting........................................................................................ 79 
10.1.4 
Pregnancy reporting .............................................................................. 80 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 81 
10.2 
Additional Safety Monitoring ................................................................................ 81 
10.2.1 
Liver safety monitoring ......................................................................... 81 
 
 82 
10.2.3 
Post-mortem data collection .................................................................. 82 
10.3 
Committees ............................................................................................................ 82 
10.3.1 
Data Monitoring Committee ................................................................. 82 
11 Data Collection and Database management ...................................................................... 82 
11.1 
Data collection ....................................................................................................... 82 
11.2 
Database management and quality control ............................................................ 83 
11.3 
Site monitoring ...................................................................................................... 83 

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12 Data analysis and statistical methods ................................................................................ 84 
12.1 
Analysis sets .......................................................................................................... 84 
12.2 
Participant demographics and other baseline characteristics ................................. 84 
12.3 
Treatments ............................................................................................................. 84 
12.4 
Analysis supporting primary objectives ................................................................ 85 
12.4.1 
Definition of primary endpoint(s) ......................................................... 85 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 85 
12.4.3 
Handling of intercurrent events of primary estimand ........................... 85 
12.4.4 
Handling of missing values not related to intercurrent event ............... 85 
12.4.5 
Sensitivity analyses ............................................................................... 85 
12.4.6 
Supplementary analysis ......................................................................... 85 
12.5 
Analysis supporting secondary objectives ............................................................. 85 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 86 
 
 86 
12.7 
Interim analyses ..................................................................................................... 88 
12.8 
Sample size calculation.......................................................................................... 88 
 
 88 
13 Ethical considerations and administrative procedures ...................................................... 89 
13.1 
Regulatory and ethical compliance ........................................................................ 89 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 89 
13.3 
Publication of study protocol and results............................................................... 89 
13.4 
Quality Control and Quality Assurance ................................................................. 90 
13.5 
Participant Engagement ......................................................................................... 90 
14 Protocol adherence ............................................................................................................ 90 
14.1 
Protocol amendments............................................................................................. 91 
15 References ......................................................................................................................... 92 
16 Appendices ........................................................................................................................ 96 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 96 
16.2 
Appendix 2: Liver laboratory triggers & follow-up monitoring requirements ...... 97 
16.2.1 
Liver laboratory triggers ....................................................................... 97 
16.2.2 
Follow-up requirements for liver laboratory triggers ALT and AST, 
with and without TBL ........................................................................... 97 
16.2.3 
Follow-up requirements for liver laboratory triggers - isolated 
hyperbilirubinemia ................................................................................ 98 
16.2.4 
Prednisolone dosing ............................................................................ 100 
16.3 
Appendix 3: Specific Renal Alert Criteria and Actions and Event Follow-up .... 101 

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List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 26 
Table 4-1 
Rationale for study design ..................................................................... 30 
Table 6-1 
Investigational drug ............................................................................... 37 
Table 6-2 
Prednisolone prophylaxis ...................................................................... 38 
Table 8-1 
Assessment Schedule ............................................................................ 47 
 
 59 
Table 16-1 
Follow-up requirements for liver laboratory triggers – ALT and 
AST, with and without TBL.................................................................. 97 
Table 16-2 
Follow-up requirements for liver laboratory triggers - isolated 
hyperbilirubinemia ................................................................................ 98 
 
List of figures 
Figure 1-1 
Clinical classifications according to onset, milestones achieved, 
and clinical presentation - typically associated SMN2 copy 
numbers are displayed ........................................................................... 24 
Figure 1-2 
OAV101 vector construct ..................................................................... 26 
Figure 3-1 
Study design .......................................................................................... 30 
Figure 8-1 
Timing of study procedures .................................................................. 66 
 

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List of abbreviations 
AAV 
Adeno-associated Virus 
AAV9 
adeno-associated virus serotype 9 
ACEND 
Assessment of Caregiver Experience in Neuromuscular Disease 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ASO 
Antisense oligonucleotide 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
Beta-hCG 
Blood beta-human chorionic gonadotropin 
BIL 
Bilirubin 
BMI 
Body Mass Index 
 
 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CB 
Chicken-β-Actin-Hybrid 
cDNA 
Complementary Deoxyribonucleic Acid 
CE 
Clinical Evaluator 
CFR 
Code of Federal Regulations 
 
 
 
 
 
 
CI 
confidence interval 
CK 
Creatine Kinase 
ClinRO 
Clinician Reported Outcomes 
CMO&PS  
Chief Medical Office and Patient Safety 
CMV 
Cytomegalovirus 
CNS 
Central Nervous System 
CO 
Country Organization 
COA 
Clinical Outcome Assessment 
COVID-19 
Coronavirus disease of 2019 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CSF 
Cerebrospinal fluid 
 
 
CSR 
Clinical study report 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic Acid 
DRG 
Dorsal Root Ganglia 
EBV 
Epstein Barr Virus 
ECG 
Electrocardiogram 
eCOA 
Electronic Clinical Outcome Assessment 
eCRF 
electronic Case Report Form 

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eCRS 
electronic Case Retrieval Strategy 
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
EOS 
End of Study 
eSAE 
Electronic Serious Adverse Event 
ESE2 
Exonic splicing enhancer 2 
eSource 
Electronic Source 
eTMF 
Electronic trial master file 
EU 
European Union 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials Database 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in the first second 
FIVC 
forced inspiratory vital capacity 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GLDH 
Glutamate Dehydrogenase 
HAV 
Hepatitis A Virus 
HBc 
Hepatitis B core 
HBsAg 
Hepatitis B virus surface antigen 
HBV 
Hepatitis B Virus 
hCG 
human chorionic gonadotropin 
HCO3 
Bicarbonate 
HCV 
Hepatitis C Virus 
HEENT 
Head, Eyes, Ears, Nose and Throat 
HEV 
Hepatitis E 
HFMSE 
Hammersmith Functional Motor Scale Expanded 
HIV 
Human immunodeficiency virus 
HSV 
Herpes Simplex Virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP 
Investigational Medicinal Product 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IT 
intrathecal 
ITR 
Inverted terminal repeats 
IUD 
Intrauterine device 

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IV 
intravenous 
kg 
kilogram(s) 
LDH 
lactate dehydrogenase 
LFT 
Liver function test  
LLN 
lower limit of normal 
LP 
lumbar puncture 
LS 
least squares (LS) 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical dictionary for regulatory activities  
mg 
milligram(s) 
 
 
mL 
milliliter(s) 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger ribonucleic acid 
 
 
ObsRO 
Observer Reported Outcomes 
PA 
posterior to anterior 
PICU 
Pediatric intensive care unit 
PIP 
Paediatric Investigation Plan 
PNCR 
Pediatric Neuromuscular Clinical Research 
PT 
prothrombin time 
QMS 
Quality Management System 
QTcF 
QT interval corrected by Fridericia’s formula 
rAAV 
Recombinant adeno-associated virus 
 
 
RNA 
Ribonucleic acid 
RULM 
Revised Upper Limb Module 
SAE 
Serious Adverse Event 
SAF 
Safety analysis set 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SMA 
Spinal muscular atrophy 
SMN 
Survival of Motor Neuron 
SMN1 
Survival of Motor Neuron 1 
SMN2 
Survival of Motor Neuron 2 
SmPC 
Summary of Product Characteristics 
SNAP 
Sensory nerve action potential 
SOC 
System organ class 
SOP 
standard operating procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TBL 
Total bilirubin 
ULN 
upper limit of normal 

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US 
United States 
vg 
vector genome 
WBC 
White blood cells 
WHO 
World Health Organization  
WOB 
work of breathing 
WoC 
Withdrawal of Consent 

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Glossary of terms 
(5q)SMA 
Spinal muscular atrophy caused by bi-allelic defects in the survival motor neuron 1 
(SMN1) gene on chromosome 5q13.2 leading to a deficiency in the SMN1 protein 
Additional treatment 
Medicinal products that may be used during the clinical trial as described in the 
protocol, but not as an investigational medicinal product (e.g. any background 
therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, 
tissue, urine, stool, etc. taken from a study participant  
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, functions, or survives 
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting of all 
clinical trial activities. Examples of team members include the Study Lead, Medical 
Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center team by 
replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, experience or 
characteristic, or a group of individuals followed-up or traced over time 
Control drug 
A study drug (active or placebo) used as a comparator to reduce assessment bias, 
preserve blinding of investigational drug, assess internal study validity, and/or 
evaluate comparative effects of the investigational drug 
Discontinuation from 
study 
Point/time when the participant permanently stops receiving the study treatment 
and further protocol required assessments or follow-up, for any reason. No specific 
request is made to stop the use of their samples or data. 
Discontinuation from 
study treatment 
Point/time when the participant permanently stops receiving the study treatment 
for any reason (prior to the planned completion of study drug administration, if 
any). Participant agrees to the other protocol required assessments including 
follow-up. No specific request is made to stop the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 100 mg 
once a day, 75 mg twice a day) 
Electronic Data Capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data 
using data collection systems, such as Web-based applications, interactive voice 
response systems and clinical laboratory interfaces. EDC includes the use of 
Electronic Case Report Forms (eCRFs) which are used to capture data transcribed 
from source data/documents used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last participant 
Enrollment 
Point/time of participant entry into the study at which informed consent must be 
obtained. The action of enrolling one or more participants 
eSource (DDE) 
eSource Direct Data Entry (DDE) refers to the capture of clinical study data 
electronically, at the point of care. eSource Platform/Applications combines source 
documents and case report forms (eCRFs) into one application, allowing for the 
real time collection of clinical trial information to sponsors and other oversight 
authorities, as appropriate 
Estimand 
As defined in the ICH E9(R1) addendum, estimand is a precise description of the 
treatment effect reflecting the clinical question posed by the trial objective. It 
summarizes at a population-level what the outcomes would be in the same 
participants under different treatment conditions being compared. Attributes of an 
estimand include the population, variable (or endpoint) and treatment of interest, 
as well as the specification of how the remaining intercurrent events are addressed 
and a population-level summary for the variable. 
Intercurrent events 
Events occurring after treatment initiation that affect either the interpretation or the 
existence of the measurements associated with the clinical question of interest. 

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Study treatment 
Any drug or combination of drugs or intervention administered to the study 
participants as part of the required study procedures; includes investigational 
drug(s), control(s) or background therapy 
Tele-visit 
Procedures or communications conducted using technology such as telephone or 
video-conference, whereby the participant is not at the investigative site where the 
investigator will conduct the trial. 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the combination, and may 
consist of 1 or more cohorts. 
Treatment of interest 
The treatment of interest and, as appropriate, the alternative treatment to which 
comparison will be made. These might be individual interventions, combinations of 
interventions administered concurrently, e.g. as add-on to standard of care, or 
might consist of an overall regimen involving a complex sequence of interventions. 
This is the treatment of interest used in describing the related clinical question of 
interest, which might or might not be the same as the study treatment. 
Variable (or endpoint) 
The variable (or endpoint) to be obtained for each participant that is required to 
address the clinical question. The specification of the variable might include 
whether the participant experiences an intercurrent event. 
Withdrawal of consent 
(WoC) / Opposition to 
use of data /biological 
samples 
Withdrawal of consent from the study occurs when the participant explicitly 
requests to stop use of their data and biological samples (opposition to use data 
and/or biological samples) AND no longer wishes to receive study treatment, AND 
does not agree to further protocol required assessments. This request should be in 
writing (depending on local regulations) and recorded in the source 
documentation. 
Opposition to use data/biological samples occurs in the countries where collection 
and processing of personal data is justified by a different legal reason than 
consent. 
 

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incorporation of AAV vector DNA into chromosomal DNA that has been noted based 
on published literature for AAV-based therapies. 
• Risk terminology has been updated to “transient thrombocytopenia”  to align with 
eCRS.  
• Maximum blood volume withdrawn for patients has been added. In line with EU 
Regulation No 536/2014 (European Commission 2017).  
• Section 4.6 Rationale for Public Health Emergency Mitigation Procedures: 
• Rationale for Public Health Emergency mitigation procedures – wording revision to 
align with the latest Novartis Protocol template. 
• Section 5 Study Population:  
• The total population age group has expanded from 2-12 years to 2-<18 years. The 
sample size remains the same at approximately 28 patients. Age of participants 
enrolled will be stratified as 2-5 years or  6-< 18 years, with approximately 12 
subjects in each stratum. 
• Section 5.1 Inclusion Criteria:  
• Inclusion criterion #3 has been amended to include patients from 2 to < 18 years of 
age to cover the full pediatric age range and for consistency with the study population 
age range for another Novartis ongoing Phase 3 COAV101B2301 trial in treatment 
naïve patients aged 2 to <18 years. Sample size assumptions remain unchanged. 
• Section 5.2 Exclusion Criteria: 
• Exclusion criterion #6 has been clarified to specify exclusion of ‘clinically 
significant’ abnormal results to allow investigator discretion in case of minimally 
abnormal coagulation results.  
• Exclusion criterion #14 has been edited to apply if an infection is present within 30 
days prior of OAV101 versus “at any time” during screening and additionally for 
febrile illnesses  “within two weeks prior to Screening visit 1” to conform to program 
standards.  
• Exclusion criterion #23 has been clarified in order to specify that ‘systemic’ 
immunosuppressive therapy is excluded. 
• Exclusion criterion #26 has been edited to remove ‘and/or sponsor’ as the sponsor 
will not make decisions on eligibility. 
• Table 6-1 Investigational Drug: 
• More details regarding the investigational drug have been added to align with the 
latest Novartis protocol template. 
• Section 6.2.1.1 Permitted concomitant therapy requiring caution and/or action: 
• Instances of ‘should’ have been changed to ‘must’ as vaccination guidance is 
mandatory to adhere to. 
• Section 6.2.2 Prohibited medication: 
• Instances where prohibited concomitant medications may be allowed, have been 
clarified. Prohibited medications are still allowed post-treatment, if medically 
indicated. 

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Protocol summary 
Protocol number 
C0AV101B12302 
Full Title 
Phase IIIb, open-label, single-arm, multi-center study to evaluate the 
safety, tolerability and efficacy of OAV101 administered intrathecally 
(1.2 x 1014 vector genomes) to participants 2 to < 18 years of age with 
spinal muscular atrophy (SMA) who have discontinued treatment with 
nusinersen (Spinraza®) or risdiplam (Evrysdi®) 
Brief title 
Safety, tolerability and efficacy study of OAV101 administered 
intrathecally to participants 2 to <18 years of age with spinal muscular 
atrophy (SMA) who have discontinued treatment with nusinersen 
(Spinraza®) or risdiplam (Evrysdi®) 
Sponsor and 
Clinical Phase 
Novartis 
Phase III 
Investigation type 
Biological 
Study type 
Interventional 
Purpose 
To characterize the safety, tolerability and efficacy of OAV101 (1.2 x 
1014 vector genomes) administered by one-time lumbar intrathecal (IT) 
injection over a 52-week period, in participants who have discontinued 
treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®). 
Primary Objective(s) 
The primary objective of this study is to characterize the safety and 
tolerability of OAV101 IT over a 52-week period in patients with SMA 
aged 2 to < 18 years who have discontinued treatment with nusinersen 
(Spinraza®) or risdiplam (Evrysdi®). 
The primary endpoints for the primary objective are: the number and 
percentage of participants reporting adverse events (AEs), related AEs, 
serious AEs and adverse events of special interest (AESIs) over a 52-
week period. 
Secondary Objectives 
The secondary objective of this study is to assess the efficacy of 
OAV101 IT on motor function and caregiver impact over a 52-week 
period in patients with SMA aged 2 to < 18 years who have 
discontinued treatment with nusinersen (Spinraza®) or risdiplam 
(Evrysdi®). 
The secondary endpoints for the secondary objective questions of 
interest are: 
● What is the change from baseline to Week 52 visit in the 
Hammersmith Functional Motor Scale Expanded (HFMSE) total score? 
● What is the change from baseline to Week 52 visit in the Revised 
Upper Limb Module (RULM) total score? 
● What is the change from baseline to Week 52 visit in Assessment of 
Caregiver Experience in Neuromuscular Disease (ACEND) instrument 
score? 

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Study design 
This is an open-label, single arm, multi-center study. Approximately 28 
participants aged 2 to < 18 years will be enrolled stratified as 2 to 5 
years and 6 to < 18 years. The study is comprised of 3 periods, 
Screening (up to 45 days), Treatment (1 day), and Follow-up (52 
weeks). 
During the Screening period and on Day -1 (Baseline), eligibility will be 
assessed, including confirmation that nusinersen 
(Spinraza®) or risdiplam (Evrysdi®) have not been used for the defined 
period (4 month and 15 days prior to Day -1 respectively). On Day - 1 
(Baseline) participants will be admitted to the hospital for pre-treatment 
baseline procedures. Prednisolone (or equivalent) will be given and 
continued as per the study protocol. 
Participants who meet eligibility criteria at Screening and Baseline will 
receive a single dose of OAV101 (1.2 x 1014 vector genomes) by lumbar 
IT injection on Day 1 (Treatment) and will then undergo in-patient safety 
monitoring over at least the next 48 hours, after which the participant 
may be discharged according to Investigator judgement. 
During Follow-up, safety monitoring will continue as per the visits 
defined in the Assessment Schedule. Safety for participants enrolled will 
be evaluated by the study team together with the Data Monitoring 
Committee (DMC) as described in the DMC charter. 
Final analysis will be performed after all participants have completed 
Week 52 or discontinued prior to Week 52. At the end of study, 
participants will be invited to enroll in a Novartis-sponsored long-term 
follow-up study to monitor long-term safety and efficacy. 
Rationale 
The data from this study will expand on the data generated from other 
studies of OAV101 IT in the treatment naive SMA population. 
Specifically, data from this study may provide safety, tolerability, and 
efficacy evidence in support of management and monitoring for patients 
with SMA who discontinue nusinersen (Spinraza®) or risdiplam 
(Evrysdi®) to receive OAV101 IT. 
Study population 
Participants with SMA with bi-allelic mutations in the survival of motor 
neuron 1 (SMN1) gene, and any number of copies of survival of motor 
neuron 2 (SMN2) gene, aged 2 to <18 years will be enrolled. The 
population will be stratified by age (2 to 5 years and 6 to <18 years with 
approximately 12 subjects in each stratum). Participants must be able to 
sit independently, but never have taken steps independently and must 
have received at least four loading doses of nusinersen (Spinraza®) or 
at least 3 months of risdiplam (Evrysdi®) to be eligible for this study. 
Key Inclusion criteria 
● Written informed consent 
● SMA diagnosis based on gene mutation analysis with bi-
allelic SMN1 mutations and any copy of SMN2 gene 
● Aged 2 to <18 years (screening visit must occur before the patient’s 
18th birthday) at time of Screening Visit 1 
● Have had at least four loading doses of nusinersen (Spinraza®) or at 
least 3 months of treatment with risdiplam (Evrysdi®) at Screening 
● Must be able to sit independently but must never have taken steps 
independently 
● Diagnosed through newborn or neonatal screening or patients 
clinically diagnosed must have age of clinical symptom onset < 18 
months 
● Meets age-appropriate institutional criteria for use of 
anesthesia/sedation 
● Female participants who are sexually active or have reached 
menarche must have a negative pregnancy test at Screening. Those 

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females who are sexually active must also agree to use highly effective 
methods of contraception. 
Key Exclusion criteria 
● Excluding SMA, any medical condition considered clinically 
significant 
● Positive for human immunodeficiency virus (HIV), hepatitis B or 
hepatitis 
●  Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using 
an immunoassay is reported as elevated at Screening (reference 
to >1:50 or a validated result consistent with being elevated) 
● Clinically significant abnormalities in test results during screening 
period and/or at Baseline 
● Platelet count less than the lower limit of normal (LLN), or platelet 
transfusion within 1 month at Screening Visit 1 
● Clinically significant abnormal coagulation panel results at 
Screening 
● Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total 
bilirubin (TBL), gamma-glutamyl transferase (GGT) or glutamate 
dehydrogenase (GLDH) > upper limit of normal (ULN) at Screening 
(with the exception of isolated AST elevation: in the absence of other 
liver laboratory abnormalities, isolated elevated AST is not considered 
exclusionary) 
● Contraindications for lumbar puncture procedure 
● At Baseline (Day-1), participants are excluded if they received: 
● 
nusinersen (Spinraza®) within 4 months at Baseline 
● 
risdiplam (Evrysdi®) within 15 days at Baseline 
● Vaccinations 2 weeks prior to administration of OAV101 
● Hospitalization for a pulmonary event, or for nutritional support 
within 2 months prior to Screening or inpatient major surgery planned. 
● Presence of the following: 
● 
An active infectious process requiring systemic antiviral or 
antimicrobial therapy up to 30 days prior to OAV101 administration, 
or 
● 
An active but untreated viral or bacterial infectious process up 
to 30 days prior to administration of OAV101, or 
● 
Any febrile illness up to 30 days prior to administration of 
OAV101 
● Requiring invasive ventilation, awake noninvasive ventilation for > 6 
hours during a 24-hour period, noninvasive ventilation for >12 hours 
during a 24-hour period or requiring tracheostomy, at Screening and up 
to OAV101 administration 
● Concomitant use of any of the following medication categories within 
90 days prior to administration of OAV101 
● 
Ongoing systemic immunosuppressive therapy (e.g., 
corticosteroids, cyclosporine, tacrolimus, methotrexate, 
cyclophosphamide, intravenous immunoglobulin, rituximab), 
plasmapheresis, immunomodulators (e.g., adalimumab) 
● History of hypersensitivity to any of the study treatments or its 
excipients or drugs of similar chemical classes 
Study treatment 
OAV101 
Treatment of interest 
Single IT administration of OAV101 at a dose of 1.2 x 1014 vector 
genomes 
Key efficacy assessments 
● HFMSE total score 

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● RULM total score 
● ACEND instrument total score 
Key safety assessments 
● Adverse event monitoring 
● Physical examination, inlcuding neurological examination 
● Vital signs 
● Laboratory values (hematology, chemistry including liver function 
tests (LFTs) and troponin I, coagulation, urinalysis) 
● Electrocardiogram 
● Echocardiogram 
● Columbia Suicide Severity Rating Scale (C-SSRS) 
● Pregnancy tests as applicable 
Other assessments 
Data analysis 
The primary estimand is described by the following attributes: 
● Population: Patients with SMA aged 2 to <18 years who were 
treated with OAV101 IT administration after the discontinuation of 
nusinersen (Spinraza®) or risdiplam (Evrysdi®). 
● Endpoint (the primary variable): AEs, related AEs, serious adverse 
events (SAEs) and AESIs. 
● Treatment of interest: OAV101 IT 
Handling of intercurrent events (including receiving prohibited 
concomitant medications): 
Treatment policy strategy, i.e., reporting all observed AEs, related AEs, 
SAEs (including death) and AESIs during the trial period, regardless 
whether intercurrent events occurred or not. Loss to follow-up does not 
impact primary estimand under treatment policy strategy. 
Summary measures: The number and percentage of participants 
reporting AEs, related AEs, SAEs and AESIs will be summarized by 
strata and overall. Summaries will also be provided by the Medical 
Dictionary for Regulatory Activities (MedDRA) system organ 
class (SOC) and preferred term. 
The secondary endpoints include change from baseline to Week 52 in 
the HFMSE total score, change from baseline to Week 52 in the RULM 
total score and change from baseline to Week 52 in the ACEND 
instrument score. 
Change from baseline to Week 52 in the HFMSE total score, change 
from baseline to Week 52 in the RULM total score and change from 

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1 
Introduction 
1.1 
Background 
Spinal Muscular Atrophy (SMA) is a neurogenetic disorder caused by a loss or mutation in the 
survival motor neuron 1 gene (SMN1) on chromosome 5q13, which leads to reduced SMN 
protein levels and a selective dysfunction of motor neurons. SMA is an autosomal recessive, 
early childhood disease with an incidence of approximately 1:10,000 live births 
(Ogino et al 2004, Sugarman et al 2012). Prior to available treatments, SMA was the leading 
cause of infant mortality due to genetic disease (Kaufmann et al 2012). A small amount of SMN 
protein (approximately 10 – 15 % of total) is also produced by the SMN2 gene. The SMN2 gene 
is 
almost 
identical 
to 
SMN1, 
but 
only 
partially 
functional 
(Rochette et al 2001, Kolb and Kissel 2011). Disease severity and clinical prognosis generally 
inversely correlate with the variable number of copies of SMN2. In the most common and severe 
form of SMA (Type 1), hypotonia and progressive weakness are recognized in the first few 
months of life, leading to diagnosis by 6 months of age and then death due to respiratory failure 
by 2 years of age. Motor neuron loss in SMA Type 1 is profound in the early postnatal period 
(or may even start in the pre-natal period), whereas patients with Type 2 and 3 SMA adapt and 
compensate during development and persist into adult life. 
In support of the hypothesis that gene copy numbers of SMN2 primarily drive phenotypic 
presentation of SMA, a large review examined the association between SMN2 copy number and 
SMA phenotype (Calucho et al 2018). The authors showed that 79% of patients with two copies 
of SMN2 developed SMA Type I, 16% developed SMA Type 2 and 5% developed SMA Type 
3; 54% of patients with three copies of SMN2 developed SMA Type 2, 31% developed SMA 
Type 3 and 16% developed SMA Type 1; and among patients with four copies of SMN2, most 
had mild SMA variants with only 1% developing SMA Type 1 and 11% developing SMA Type 
2. In keeping with the importance of SMN production by SMN2, few individuals with SMN1 
mutations and ≥6 copies of SMN2 develop symptoms and those who are affected develop only 
milder forms of SMA; while patients with one copy of SMN2 often present with more severe 
forms of SMA (Bernal et al 2010, Riessland et al 2017). 
SMA is conventionally classified into 4 phenotypes on the basis of age of onset and highest 
motor function achieved, with an additional phenotype (Type 0) to describe the severe forms of 
antenatal-onset spinal muscular atrophy (Kolb and Kissel 2011, Mercuri et al 2012). SMA 
Type 1 patients present with symptoms within the first 6 months of life and by definition never 
attain independent sitting. SMA Type 1 is the leading genetic cause of infant death. In contrast, 
SMA Type 2 manifests within the first 18 months of life and follows a slower disease 
progression as compared to SMA Type 1. Children with SMA Type 2 are able to maintain 
sitting unassisted but never walk independently and have a life expectancy of 20-40 years of 
age. SMA Type 3 patients attain the ability to walk unaided (Type 3a have onset <3 years of 
age; Type 3b have onset > 3 years of age), but untreated many of those patients will lose this 
ability at older age. SMA Type 4 is an adult onset form of the disease. Figure 1-1 summarizes 
SMA subtypes and associated clinical features as well as the relationship of the SMA subtypes 
to SMN2 copy numbers. 

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and thereby suppresses the binding of other splice-factors. This results in an increased 
proportion of SMN2-mRNA with included exon 7 and consecutively more functional full-length 
SMN2 protein (Schorling et al 2020). Following four loading doses over 58 days, nusinersen 
(Spinraza®) must be administered indefinitely every 4 months via IT injection. Nusinersen 
(Spinraza®) is approved for pediatric and adult patients with SMA. Risdiplam (Evrysdi®, 
Roche), approved by FDA in 2020 and EMA in 2021, is a small molecule, pyridazine derivative, 
that modulates SMN2 gene splicing, binding two sites in SMN2 pre-mRNA: 50 splice site (50 
ss) of intron 7 and exonic splicing enhancer 2 (ESE2) in exon 7. Risdiplam (Evrysdi®) is 
administered orally once a day and is approved for treatment of SMA in patients 2 months of 
age and older in the US. Unlike OAV101, which is a one-time gene therapy, nusinersen 
(Spinraza®) and risdiplam (Evrysdi®) require lifelong treatment in order to sustain effectiveness. 
Therefore, OAV101, which targets the main source of SMN protein and provides sustained and 
uninterruptible SMN protein levels, may offer an important treatment option to patients who 
are unwilling or unable to commit to a chronic, lifelong therapy. Additionally, individuals with 
SMA may discontinue nusinersen (Spinraza®) or risdiplam (Evrysdi®) due to other reasons (e.g., 
suboptimal efficacy, safety, compliance, burden). Data collected in the real-world show that a 
population of patients who discontinue nusinersen (Spinraza®) exists already in SMA types 1-
3. In a retrospective claims database analysis of over 300 patients, report of persistence rates of 
nusinersen (Spinraza®) use 12 months after treatment initiation is below 56% (Gauthier-
Loiselle et al 2021). The SMA-related comorbidity profile was similar per SMA-type in 
subjects who discontinued and those who did not discontinue nusinersen (Spinraza®), but SMA-
related comorbidities were increased in those patients with non-adherence for which logistical 
challenges were thought to play a role (Hache et al 2016,Gauthier-Loiselle et al 2021). Mean 
adherence rates were 71.84%, 74.37% and 75.57% for SMA Type 1, Type 2 and Type 3 
respectively, and non-adherence also led to higher health care resource utilization days and 
higher health care costs per patient per year (Gauthier-Loiselle et al 2021). Given the shorter 
time that has lapsed since risdiplam (Evrysdi®) approval, similar data on patients who may 
discontinue risdiplam (Evrysdi®) is not yet available. 
OAV101 gene therapy mechanism of action: OAV101 is a single treatment for patients with 
5q SMA. OAV101 is a non-replicating recombinant adeno‑associated virus serotype 9 (AAV9) 
containing the human SMN complementary deoxyribonucleic acid (cDNA) under the control 
of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid (CB) promoter (Figure 1-2). 
One of the two adeno-associated virus (AAV) inverted terminal repeats has been modified to 
promote intramolecular annealing of the transgene, thus forming a double-stranded transgene 
ready for transcription. 

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Objective(s) 
Endpoint(s) 
● Change from baseline to Week 52 visit in 
Assessment of Caregiver Experience in ACEND 
instrument score 

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● Number and percentage of participants with 
suicidal ideation, suicidal behavior, or self-injurious 
behavior as assessed by the C-SSRS 
2.1 
Primary estimands 
The estimand is the precise description of the treatment effect and reflects strategies to address 
events occurring during trial conduct which could impact the interpretation of the trial results. 
The primary clinical question of interest is: What is the effect on safety and tolerability of 
OAV101 IT for patients with SMA who were discontinued from treatment with nusinersen 
(Spinraza®) or risdiplam (Evrysdi®). 
The primary estimand is described by the following attributes: 
1. Population: Patients with SMA aged 2 to <18 years who were treated with OAV101 IT 
administration after the discontinuation of nusinersen (Spinraza®) or risdiplam (Evrysdi®). 
2. Endpoint (the primary variable): AEs, related AEs, SAEs and AESIs. 
3. Treatment of interest: OAV101 IT 
Handling of intercurrent events (including receiving prohibited concomitant medications): 
Treatment policy strategy, i.e., reporting all observed AEs, related AEs, SAEs (including death) 
and AESIs during the trial period, will be used regardless of whether intercurrent events 
occurred or not. Loss to follow-up does not impact primary estimand under treatment policy 
strategy. 
Summary measures: The number and percentage of participants reporting AEs, related AEs, 
SAEs and AESIs will be summarized by strata and overall. Summaries will also be provided by 
MedDRA SOC and preferred term. 

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2.2 
Secondary estimands 
The secondary clinical question of interest is: What is the effect on efficacy of OAV101 IT for 
patients with SMA who were discontinued from treatment with nusinersen (Spinraza®) or 
risdiplam (Evrysdi®). 
The secondary estimand is described by the following attributes: 
1. Population: Patients with SMA aged 2 to < 18 years who were treated with OAV101 IT 
administration after the discontinuation of nusinersen (Spinraza®) or risdiplam (Evrysdi®). 
2. Endpoint (the secondary variable): Change from baseline to Week 52 in the HFMSE total 
score, change from baseline to Week 52 in the RULM total score, and change from 
baseline to Week 52 in the ACEND instrument total score. 
3. Treatment of interest: OAV101 IT 
The intercurrent events will include receiving prohibited concomitant medications, study 
discontinuation due to any reason. All available assessments collected up to Week 52 visit / 
EOS visit regardless intercurrent events will be included in the analyses following a treatment 
policy strategy. 
Summary measures: mean changes from baseline in HFMSE total score, RULM total score as 
well as ACEND instrumental total score. 
3 
Study design 
This is a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability 
and efficacy of OAV101 IT in patients with SMA aged 2 to < 18 years after the discontinuation 
of treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®). The study is comprised of 3 
periods, Screening (includes Baseline), Treatment, and Follow-up (Figure 3-1). 
Screening Period 
Participants will undergo screening procedures for up to 45 days prior to OAV101 IT treatment 
(Screening Visit 1 and Screening Visit 2 as detailed in Table 8-1) during which time initial 
eligibility will be determined (pending confirmation of all criteria including time off nusinersen 
(Spinraza®) or risdiplam (Evrysdi®) treatment at Baseline). 
The eligibility criterion relating to timeframe of nusinersen (Spinraza®) or risdiplam (Evrysdi®) 
discontinuation treatment will be confirmed at Baseline on Day -1. 
On Day -1, eligible participants will be admitted to the hospital for pre-treatment Baseline 
procedures (Table 8-1) including prednisolone treatment per study protocol (or an equivalent 
corticosteroid, Section 6.2). 
Treatment Period 
On Day 1, participants meeting Screening and Baseline eligibility criteria will receive lumbar 
puncture with CSF withdrawal for analyses in accordance with the Assessment Schedule  
(Table 8-1) and receive a single IT injection of OAV101. Following OAV101 administration, 
participants will undergo in-patient safety monitoring over at least the next 48 hours  
(Table 8-1). 

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Duration of prior SMA therapy 
Participants included in this study are required to 
have had at least four loading doses of nusinersen 
(Spinraza®) or at least 3 months of treatment with 
risdiplam (Evrysdi®) prior to Baseline (Day-1). This is 
to ensure the participants are exposed to previous 
treatments of nusinersen (Spinraza®) or risdiplam 
(Evrysdi®), and for clinicians to determine a 
risk/benefit profile of OAV101 in treatment 
experienced patients. 
Time off prior SMA therapy 
Participants should have received their latest dose of 
prior medication at least 4 months prior to the 
Baseline Visit (Day -1) for nusinersen (Spinraza®) 
or at least 15 days prior to the Baseline Visit (Day -1) 
for risdiplam (Evrysdi®). For nusinersen (Spinraza®), a 
period of 4 months will allow participants to receive 
OAV101 at the same time when their next 
maintenance dose of nusinersen (Spinraza®) would 
have been due, though some participants may also 
have discontinued nusinersen (Spinraza®) prior to 
this. For risdiplam (Evrysdi®) (half-life 2 days), a 
period of 15 days will result in >99% of the drug being 
cleared from the plasma. 
4.1.1 
Rationale for choice of background therapy 
The study allows for standard of care, non‑disease modifying SMA therapy, including 
respiratory and nutritional support; physical, occupational, and speech-language therapies; 
other forms of supportive therapies are allowed but the frequency should remain the same 
during the clinical study, if possible. Prevention of infection therapies should be conducted in 
accordance with treatment guidelines and local practice. 
Participants are expected to have access to respiratory equipment (e.g. cough assist machine) in 
the event they are required during the course of the study (e.g. develop a respiratory illness). 
The use of concomitant therapies or procedures must be documented on the appropriate Case 
Report Form (CRF) (see Section 6.2.1) 
4.2 
Rationale for dose/regimen and duration of treatment 
OAV101 will be administered in this trial as a single IT injection as a nominal dose of 1.2 x 
1014 vector genomes (vg). This dose was selected for assessment in this study based on the 
totality of clinical and nonclinical data, taking into consideration well established literature 
showing constant CSF volumes from 2 years of age into adulthood (Matsuzawa et al 2001). The 
AVXS-101-CL-102 trial explored the safety and efficacy of OAV101 IT in SMA type-2 
patients between 6 months and 5 years of age at three doses; Dose A (N=3; 6.0 x 1013 vg), Dose 
B (N=25; 1.2 x 1014 vg) and Dose C (N=4; 2.4 x 1014 vg). Robust motor improvements were 
seen in the older ≥ 24 months to <5-year age group who were treated with dose B (1.2 x 1014 
vg). These improvements were statistically significant and clinically meaningful; the estimated 
difference (95% confidence interval [CI]) relative to the Pediatric Neuromuscular Clinical 
Research (PNCR) dataset for the change in HFMSE from baseline to Month 12 was 5.5 (1.9, 
9.0) points, with a p-value of 0.0027. In these older patients, 11/12 (91.7%) patients achieved 
the ≥3-point change in HFMSE, which is usually accepted to demonstrate clinically meaningful 

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improvement 
in 
the 
HFMSE 
(Krosschell et al 2011, Mercuri et al 2018b). 
Dose 
B 
demonstrated clear clinical efficacy in Study AVXS-101-CL-102. More information on safety 
of OAV101 IT can be found in the Investigator's Brochure. Based on the totality of available 
non-clinical and clinical data, the flat dose of 1.2 x1014 vg patient administered intrathecally is 
appropriate for the patient population in this study. 
4.3 
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs 
Not applicable 
4.4 
Purpose and timing of interim analyses/design adaptations 
Interim analyses may be conducted for internal decision-making purposes, in response to health 
authority requests, and/or for purposes of scientific publication. 
4.5 
Risks and benefits 
OAV101 IT can achieve sustained expression of SMN in motor neurons with one‑time dosing, 
which can fulfil a clear unmet need in SMA patients unable to commit to chronic, lifelong 
therapy. 
Uninterruptable and constant SMN protein production within motor neurons positively impacts 
the clinical phenotype by allowing motor development which leads to stability in motor function. 
Clinical data to date suggest OAV101 is well tolerated with an acceptable benefit/risk profile 
when administered to patients with 5qSMA with 2 or 3 survival motor neuron 2 (SMN2) copies 
or a clinical diagnosis of SMA. Safety and clinically meaningful efficacy with IT delivery of 
OAV101 was observed in the AVXS-101-CL-102 trial. 
The AVXS-101-CL-102 trial explored the safety and efficacy of OAV101 IT in SMA Type-2 
patients between 6 months and 5 years of age at three doses; Dose A (N=3; 6.0 x 1013 vg), Dose 
B (N=25; 1.2 x 1014 vg) and Dose C (N=4; 2.4 x 1014 vg). Robust motor improvements were 
seen in the older ≥ 24 months to <5-year age group who were treated with dose B (1.2 x 1014 vg). 
These improvements were statistically significant and clinically meaningful; the estimated 
difference (95% confidence interval [CI]) relative to the PNCR dataset for the change in 
HFMSE from baseline to Month 12 was 5.5 (1.9, 9.0) points, with a p-value of 0.0027. In these 
older patients, 11/12 (91.7%) patients achieved the ≥3-point change in HFMSE, which is 
usually accepted to demonstrate clinically meaningful improvement in the HFMSE 
(Krosschell et al 2011, Mercuri et al 2018b). Dose B demonstrated clear clinical efficacy in 
Study AVXS-101-CL-102 study. 
Each of the following is an important identified or important potential risk associated with 
OAV101: 
• Hepatotoxicity 
• Transient thrombocytopenia 
• Thrombotic microangiopathy 
• Cardiac adverse events 

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Summary 
In summary, available data suggest OAV101 IT one-time administration can provide a stable 
source of SMN protein via replacement of SMN1, and has the potential to improve the SMA-
related comorbidity profile in these patients, as well as removing issues such as compliance and 
long-term burden associated with chronic therapies. 
4.6 
Rationale for Public Health Emergency mitigation procedures 
During a Public Health emergency as declared by Local or Regional authorities i.e. pandemic, 
epidemic, or natural disaster, mitigation procedures to ensure participant safety and trial 
integrity may be implemented. Notification of the Public health emergency as declared by local 
or regional authorities should be discussed among investigators and Novartis. All procedures 
adapted to the situation must be submitted, if required as per local regulations, through a 
protocol amendment for approval by local or regional Health Authorities and Ethics 
Committees prior to implementation of mitigation procedures. 
5 
Study Population 
Approximately 28 participants with SMA with bi-allelic mutations in the SMN1 gene aged 2 to 
< 18 years (screening visit must occur before the patient’s 18th birthday) will be enrolled 
stratified as 2 to 5 years and 6 to < 18 years with approximately 12 subjects in each stratum. 
Participants must have received at least four loading doses of nusinersen (Spinraza®) or at least 
3 months of risdiplam (Evrysdi®) for the treatment of SMA. 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Written informed consent must be obtained before any assessment is performed 
2. SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations and any 
copy of SMN2 gene 
3. Aged 2 to <18) years of age at time of Screening Visit 1 
4. Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of 
treatment with risdiplam (Evrysdi®) at Screening 
5. Must be able to sit independently but must never have taken steps independently 
• Definition of sitting independently: Child sits up straight with the head erect for at 
least 10 seconds. Child does not use arms or hands to balance body or support 
position (Wijnhoven et al 2004). 
6. Diagnosed through newborn or neonatal screening or patients clinically diagnosed must 
have age of clinical symptom onset < 18 months 
7. Meets age-appropriate institutional criteria for use of anesthesia/sedation as assessed by 
the physician responsible for administering anesthesia/sedation 
8. Must obtain bilateral radial and sural nerve SNAPs at Screening 
9. Female participants who are sexually active or have reached menarche must have a 
negative pregnancy test at Screening. Those females who are sexually active must also 

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agree to use highly effective methods of contraception (implants, injectables, oral 
contraceptives [hormonal], intrauterine devices (IUDs), total abstinence) as well or limit 
sexual activity to surgically sterilized or contraception-practicing partners during the trial 
and for 24 months after the administration of the investigational product. Female 
participants must agree to refrain from egg freezing and egg donation until 24 months 
after dosing. Note: In case of use of oral contraceptives, females should have been stable 
on the same pill for a minimum of 3 months before OAV101 administration. If local 
regulations deviate from the contraception methods listed above to prevent pregnancy, 
local regulations apply and will be described in the informed consent form (ICF). 
10. Males capable of fathering a child must agree to use barrier contraception (combination of 
a condom and spermicide) or be abstinent for 6 months after OAV101 administration. In 
addition, male patients must agree to refrain from sperm donation or 12 months after 
OAV101 administration. 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
1. Excluding SMA, any medical condition considered clinically significant by the 
Investigator, including permanent ventilatory support, cardiomyopathy, hepatic 
dysfunction, kidney disorder, endocrine disorder including diabetes mellitus, 
gastrointestinal disorders, metabolic disorders, severe respiratory compromise and 
significant brain abnormalities at either Screening or Baseline visits 
2. Positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C 
3. Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is 
reported as elevated at Screening (reference to > 1:50 or a validated result consistent with 
being elevated) 
4. Platelet count less than the lower limit of normal at Screening 
5. Platelet transfusion within 1 month prior to Screening Visit 1 and up to administration of 
OAV101 
6. Clinically significant abnormal coagulation panel results at Screening 
7. Hepatic dysfunction (i.e. ALT, TBL, GGT or GLDH > ULN) at Screening (with the 
exception of isolated aspartate aminotransferase (AST) elevation: in the absence of other 
liver laboratory abnormalities, isolated elevated AST is not considered exclusionary) 
8. Clinically significant abnormalities in test results during screening period and/or at 
Baseline as determined by the Investigator 
9. Contraindications for lumbar puncture procedure (including but not limited to cutaneous 
infection at the treatment site, and signs or symptoms of increased intracranial pressure), 
active administration of any intrathecal therapy, presence of an implanted shunt for the 
drainage of CSF, presence of implanted CNS catheter, or any impediment to CSF access 
10. Conditions, as determined by the investigator, that would interfere with the intrathecal 
administration/lumbar puncture procedure (e.g., severe scoliosis) 
11. At Baseline (Day -1), participants are excluded if they received: 
• nusinersen (Spinraza®) within 4 months at Baseline 

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• risdiplam (Evrysdi®) within 15 days at Baseline 
12. Vaccinations 2 weeks prior to administration of OAV101 
13. Participants will be excluded for hospitalization for a pulmonary event, or hospitalization 
for nutritional support within 2 months prior to Screening and up to administration of 
OAV101. In addition, patients will not be eligible if during Screening, inpatient major 
surgery is planned at any time during the 52-week follow up period of the study 
14. Presence of any of the following: 
• An active infectious process requiring systemic therapy intended to eliminate the 
infection up to 30 days prior to administration of OAV101 
• An active but untreated viral or bacterial infectious process up to 30 days prior to 
administration of OAV101 
• Any febrile illness up to 30 days prior to administration of OAV101 
15. Clinical or radiological signs of aspiration within 4 weeks prior to Screening Visit 1 and 
up to administration of OAV101 
16. Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours during a 24-
hour period, noninvasive ventilation for > 12 hours during a 24-hour period or requiring 
tracheostomy at Screening and up to administration of OAV101 
17. Awake hypoxemia (defined as O2 saturation <95% in room air) at Screening and up to 
administration of OAV101 
• NOTE: For altitudes >1000 m, awake hypoxemia is defined as O2 saturation <92% in 
room air 
18. BMI < 3rd percentile at Screening if considered clinically significant by the investigator 
based on the WHO Child Growth Standards (WHO 2022a) and WHO Growth reference 
data for 5-19 years (WHO 2022b). 
19. Inability to tolerate corticosteroids administered by mouth or gastrostomy tube 
20. History of gene therapy, hematopoietic transplantation, or solid organ transplantation 
21. Current or scheduled participation in another investigational trial in which the participant 
receives treatment, or use of other investigational drugs within 30 days prior to Screening 
Visit 1, 5 half-lives prior to Screening Visit 1 or during the screening period (small 
molecules), or until the expected pharmacodynamic effect has returned to baseline (e.g. 
for biologics), whichever is longer; or longer if required by local regulations. 
• NOTE: Participation in observational cohort studies or non-interventional studies in 
which the participant does not receive treatment or undergo procedures which may 
compromise this study data integrity may be allowed following Sponsor approval. 
22. Plan to take any other investigational therapies relating to SMA while participating in this 
study 
23. Concomitant use of any of the following medication categories within 90 days prior to 
administration of OAV101: 
• Ongoing systemic immunosuppressive therapy (e.g.,corticosteroids [except 
prophylactic use before OAV101 IT injection], cyclosporine, tacrolimus, 

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methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab), 
plasmapheresis, immunomodulators (e.g., adalimumab) 
24. History of hypersensitivity to any of the study treatments or its excipients or drugs of 
similar chemical classes 
25. History of untreated or uncorrected vitamin deficiencies which can produce sensory 
neuropathies such as pyridoxine deficiency (Vitamin B6) 
26. Any medication deemed by Principal Investigator to pose an unacceptable safety risk for 
gene therapy administration 
27. Clinically significant sensory abnormalities in the neurological examination at Screening 
6 
Treatment 
The investigational drug, OAV101, will be prepared by Novartis and supplied to the study-site 
pharmacist or equivalent per local practice. The pharmacist (or equivalently trained individual 
per local practice) will prepare the appropriate dosage (detailed instructions will be provided in 
the Pharmacy Manual). 
6.1 
Study treatment 
For this study, the terms “investigational drug” or “study treatment” refers to OAV101 
administered as a single IT dose of 1.2 x 1014 vector genomes. The investigational drug 
OAV101 will be prepared and supplied by Novartis. See the Pharmacy Manual for OAV101 
storage, preparation, and administration procedures. 
6.1.1 
Investigational and control drugs 
The biological product is a non-replicating recombinant AAV9 containing the cDNA of the 
human SMN gene under the control of the CMV enhancer/CB promoter. The AAV inverted 
terminal repeats (ITR) has been modified to promote intramolecular annealing of the transgene, 
thus forming a double-stranded transgene ready for transcription. This modified ITR, termed a 
“self-complementary” (sc) ITR, has been shown to significantly increase the speed of which 
the transgene is transcribed, and the resulting protein is produced. The biological product, called 
OAV101, expresses the human SMN protein in transduced cells.  
Table 6-1 
Investigational drug 
Treatment title 
OAV101 (formerly AVXS-101) 
Treatment description 
1.2 x 1014 vector genomes in 3 ml, one time 
Type 
Biologic 
Dose Formulation 
Solution 
Route of Administration 
Intrathecal injection 
Use 
Experimental 
IMP 
Yes 
Sourcing 
Provided centrally by the sponsor or locally by designee 
Packaging and Labeling 
Study treatment will be provided in a single vial carton.  
Each vial carton will be labeled as required per country requirement. 

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6.2.1 
Concomitant therapy 
The Investigator should instruct the participant and his/her parent(s)/caregiver(s) to notify the 
study site about any new medications taken by the participant after enrollment into the 
study. All medications, procedures, and significant non-drug therapies administered after the 
participant was enrolled into the study must be recorded on the appropriate CRFs, including 
nusinersen or risdiplam. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication (Section 5.2 and Section 6.2.2). If in doubt, the Investigator should contact the 
Novartis medical monitor before enrollment of a participant or allowing a new medication to 
be started. If the participant is already enrolled, contact Novartis to determine if the participant 
should continue participation in the study. 
Prior medications excluded according to the criteria in Section 5.2 will be recorded within 90 
days prior to Screening and all prior medications will be recorded on the eCRF at all visits prior 
to Baseline. If the participant's last dose of nusinersen or risdiplam was beyond 90 days prior to 
Screening, this must still be recorded on the eCRF. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Participants are encouraged to follow all routinely scheduled immunizations, recommended by 
local health authorities and consistent with  Section 6.2.2, throughout the study. Where feasible, 
the participant’s vaccination schedule should be adjusted to accommodate concomitant 
corticosteroid administration prior to and following OAV101, specifically vaccinations must be 
withheld 2 weeks pre OAV101 administration, and live vaccines must not be administered 
while receiving corticosteroids. 
Participants and caregivers should be advised to follow local site guidelines on vaccination 
against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). For participants 
who are required to receive vaccination for SARS-CoV-2, the vaccination series (if multi-dose 
regimen) must be completed at least 2 weeks prior to OAV101 administration. For participants 
already in the study, potential benefits for vaccination against SARS-CoV-2 should be assessed 
on a case-by-case basis and is at the discretion of the Investigator. If a live/attenuated SARS-
CoV-2 vaccine becomes available, participants are advised to complete the vaccination series 
prior to enrolling in the study, and such vaccines are prohibited while receiving corticosteroids. 
Vaccinations must be recorded as a concomitant medication. 
6.2.2 
Prohibited medication 
Except for concomitant medication allowed per protocol (see Section 6.2.1) and/or any 
non‑excluded medications which may be medically indicated, no medication other than study 
treatment will be allowed from the date the informed consent is signed until all of the study 
completion evaluations have been performed. 
Concomitant use of any of the following medications are prohibited: 
• Concomitant medication with the intent to treat SMA, including nusinersen and risdiplam 
beyond the cut-off time. 

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• Any investigational medication other than OAV101 
• Plasmapheresis and immunomodulators (except prednisolone or equivalent, for 
prophylaxis or treatment of adverse events), unless medically indicated. 
• Use of non-live vaccines 4 weeks after injection of OAV101; unless medically indicated 
• Live vaccines are prohibited while receiving corticosteroids. Participants are advised to 
complete all age-appropriate inoculations with live vaccines prior to enrolling in the study 
if possible. 
• The use of immunosuppressive therapies, including but not limited to, cyclosporine, 
tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulins, rituximab, 
and adalimumab; unless medically indicated. 
• Hepatotoxic agents, unless medically indicated. 
Given the nature and profile of the treatment, i.e., gene therapy, there are no drug interactions 
expected. 
The Investigator should instruct the participant/caregiver to notify the study site about any new 
treatments the participant takes after the start of study treatment. All prohibited medications and 
significant non-drug therapies administered after the participant starts study treatment must be 
recorded in the eCRF. 
6.3 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational 
and control drugs section. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the Interactive Response Technology (IRT) and obtaining the medication 
number(s).As per Section 4.6, during a Public Health emergency as declared by Local or 
Regional authorities i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site 
study visits, at-home visits may be permitted (if allowed by Local or Regional Health 
Authorities and Ethics Committees as appropriate). In this case, regular phone calls or virtual 
contacts per the Assessment Schedule (Table 8-1) will occur between the site and the participant 
for instructional purposes, safety monitoring, drug accountability, investigation of any adverse 
events, ensuring participants continue to benefit from treatment and discussion of the 
participant´s health status until the participants can resume visits at the study site. 
OAV101 will arrive as outlined in the Pharmacy Manual. A single administration of OAV101 
will be prepared by an appropriately trained pharmacist (or equivalent). Preparation of OAV101 
will be done aseptically under sterile conditions at the site per Pharmacy Manual. OAV101 IT 
will be administered in the appropriate setting with immediate access to acute critical care 
management. The investigational delivery system will be prepared and used in accordance with 
the Pharmacy Manual. 

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6.3.1 
Handling of study treatment and other treatment 
6.3.1.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only designated site personnel have 
access. Upon receipt, all study treatment must be stored according to the instructions 
specified in the Pharmacy Manual. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Country Organization (CO) Quality 
Assurance. Please refer to procedures as outlined in the Pharmacy Manual. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 
The designated site personnel must maintain an accurate record of the shipment and dispensing 
of study treatment in a drug accountability log. Monitoring of drug accountability will be 
performed by monitors during site visits or remotely and at the completion of the trial. 
At the conclusion of the study, and as appropriate during the course of the study, the designated 
site personnel will return the completed drug accountability log to the Novartis monitor or to 
the Novartis address provided in the investigator folder at each site. 
OAV101 kits will be stored in a locked, limited access room under the responsibility of the 
Investigator or other authorized persons (e.g., pharmacists) in accordance with local regulations, 
policies, and procedures. Control of storage conditions, especially control of temperature (e.g., 
refrigerated/freezer storage) and information on in-use stability and instructions for handling 
prepared OAV101 should be managed in accordance with the Pharmacy Manual. 
Any quality issue noticed with the receipt or use of OAV101 (e.g., deficiency in condition, 
appearance, pertaining to documentation, labeling, expiration date, etc.) should be promptly 
reported to the Sponsor in accordance with procedures outlined in the Pharmacy Manual. 
Under no circumstances will the Investigator supply OAV101 to a third party, allow OAV101 
to be used other than as directed by this clinical trial protocol, or dispose of OAV101 in any 
other manner. 
6.3.1.2 
Handling of other treatment 
Not applicable 
6.4 
Participant numbering, treatment assignment, randomization 
6.4.1 
Participant numbering 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. A new Participant No. will be assigned at every 
subsequent enrollment if the participant is re-screened, as a result of screen failure. The 

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Participant No. consists of the Center Number (Center No.) (as assigned by Novartis to the 
investigative site) with a sequential participant number suffixed to it, so that each participant’s 
participation is numbered uniquely across the entire database. Upon signing the informed 
consent form, the participant is assigned to the next sequential Participant No. available. 
The Investigator or designated staff will contact the IRT and provide the requested identifying 
information to register the participant. Once assigned, the Participant No. must not be reused 
for any other participant and the Participant No. for that individual must not be changed unless 
the participant is re-screened. The site should select the eCRF book with a matching Participant 
Number from the EDC system to enter data. If the participant fails to be treated for any reason, 
the IRT must be notified within 2 days that the participant was not treated. Re-screening is 
allowed once for participants that were initially screen failures for any reason. All eligibility 
criteria must be re-checked and met prior to enrollment of the participant into the study. A new 
Participant No. should be assigned for all re-screened participants. 
A new ICF will need to be signed if the investigator chooses to re-screen the participant after a 
participant has screen failed, and the participant will be assigned a new Participant No. 
6.4.2 
Treatment assignment, randomization 
This is an open-label study where all eligible participants will receive OAV101 IT. No 
randomization will be performed. 
6.5 
Treatment blinding 
Not applicable 
6.6 
Dose escalation and dose modification 
Investigational or other study treatment dose adjustments and/or interruptions are not permitted. 
OAV101 is administered once intrathecally at a fixed dose of 1.2 x 1014 vector genomes. 
6.6.1 
Definitions of dose limiting toxicities (DLTs) 
Not applicable 
6.6.2 
Dose modifications 
Not applicable 
6.6.3 
Follow-up for toxicities 
Not applicable 

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6.7 
Additional treatment guidance 
6.7.1 
Treatment compliance 
OAV101 will be administered as a one-time IT injection. If the dose is not fully completed, the 
site personnel will need to reflect total volume administered as well as the date and time of 
administration in the CRF page. 
6.7.2 
Administration procedures 
For details on sedation/anesthesia, setting, and IT administration, please refer to the Pharmacy 
Manual. 
6.7.3 
Post-administration monitoring 
Following OAV101 administration participants will return to a designated pediatric intensive 
care unit (PICU) bed, or other appropriate setting, with close monitoring of vital signs. 
Concomitant medications and all adverse events/serious adverse events will also be monitored 
and documented following dosing procedures. Participants will be kept in the PICU patient 
room or other appropriate setting with immediate access to acute critical care management for 
at   least 48 hours for closer monitoring of mental status. If there are suspected complications 
related to post- LP as assessed by the Investigator and/or proceduralist, local standard practice 
should be followed. Optional assessments will be based on local and institutional standards, and 
may include safety assessments such as magnetic resonance imaging (MRI) of brain and spine 
(Table 8-1). Other assessments should be performed as deemed necessary based on the 
Investigator and/or proceduralist discretion. Reports will be retained as source data and adverse 
events will be entered in the eCRF if applicable. 
For full details on post-administration procedures please refer to the Pharmacy Manual. 
6.7.4 
Recommended treatment of adverse events 
The Investigator will use his/her medical judgement in accordance with standard of care to treat 
adverse events. Medication and/or intervention used to medically manage AEs must be recorded 
on the appropriate CRF. At present there is insufficient information to provide specific 
recommendations regarding treatment of adverse events other than prednisolone (or an 
equivalent) used to dampen the immune reaction directed against OAV101 (Table 6-2). 
6.7.5 
Emergency breaking of assigned treatment code 
Not applicable 
7 
Informed consent procedures 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation) Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)-approved informed consent. 

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Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g., the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent, etc.). 
8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1) lists type and timing of all assessments. All data obtained 
from these assessments must be supported in the participant’s source documentation. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
(Table 8-1) or as close to the designated day/time as possible. The efficacy assessments HFSME 
and RULM may occur over more than 1 day within the visit window, but must not exceed 4 
days. Missed or rescheduled visits should not lead to automatic discontinuation. Participants 
who discontinue from the study or withdraw their consent/oppose the use of their 
data/biological samples should be scheduled for a final evaluation visit if they agree as soon as 
possible, at which time all of the assessments listed for the final visit will be performed. At this 
final visit, the AE and concomitant medications not previously reported must be recorded on 
the CRF. 
The “X” in the table denotes the assessments to be recorded in the clinical database or received 
electronically from a vendor. The “S” in the table denotes the assessments that are only in the 
participant’s source documentation and do not need to be recorded in the clinical database. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e., pandemic, epidemic or natural disaster that limits or prevents on-site study visits, 
alternative methods of providing continuing care may be implemented by the Investigator as 
the situation dictates. If allowable by a local Health Authority, national and local regulations 
and depending on operational capabilities, phone calls, virtual contacts (e.g., tele consultation) 
or visits by site staff/ off-site healthcare professional(s) to the participant´s home, can replace 
certain protocol assessments, for the duration of the disruption until it is safe for the participant 
to visit the site again. If the Investigator delegates tasks to an off-site healthcare professional, 
the Investigator must ensure the individual(s) is/are qualified and appropriately trained to 
perform assigned duties. The Investigator must oversee their conduct and remain responsible 
for the evaluation of the data collected. 

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Table 8-1 
Assessment Schedule 
Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
Informed 
consent/assent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demography 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical history/current 
medical conditions 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Information to be 
collected on screening 
failures 
X4 
X4 
X4 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
IRT contact 
X 
X 
  
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion / Exclusion 
criteria 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Sensory Nerve Action 
Potential 
(SNAP)/Electrophysiolo
gy 
X 
X5 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Chest X-ray 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prophylactic 
prednisolone 
  
  
X6 
X 
X 
X 
X 
X 
X 
X 
X 
X7 
  
  
  
  
  
  
OAV101 IT 
administration 
  
  
  
X8 
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
Post-administration 
monitoring9 
  
  
  
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
Prior medications 
X 
X 
X10 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Concomitant 
medications and 
therapies 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X11 
X11,12 X11 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BMI 
X 
 
X 
  
  
  
  
  
  
X 
  
X 
  
  
X 
X 
X 
X 
Body Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body Height 
(Segmental by Tibial 
Length) 
X 
  
X 
  
  
  
  
  
  
X 
  
X 
  
  
X 
X 
X 
X 
Neurological 
Examination13 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination14 
S 
  
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Adverse events/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Columbia Suicide 
Severity Rating Scale 
(C-SSRS)15 
  
  
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hammersmith 
Functional Motor Scale 
Expanded (HFMSE)16 
X 
  
X 
  
  
  
  
  
  
X 
  
X 
  
X 
X 
X 
X 
X 
Revised Upper Limb 
Module (RULM)16 
X 
  
X 
  
  
  
  
  
  
X 
  
X 
  
X 
X 
X 
X 
X 

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Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
ACEND 
  
  
X 
  
  
  
  
  
  
X 
  
X 
  
X 
X 
X 
X 
X 
BLOOD: Serum beta-
human chorionic 
gonadotropin 
pregnancy test 
(Quantitative). Female 
participants only17 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
URINE beta-human 
chorionic gonadotropin 
pregnancy test 
(Qualitative). Female 
participants only17 
  
  
  
S 
  
  
  
  
  
S 
S 
S 
S 
S 
S 
S 
S 
S 
Hepatitis Panel 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
HIV Screen 
(Antigen/Antibody with 
reflex to confirmation) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology 
X 
  
X 
  
X18 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Chemistry 
X 
  
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Troponin I 
X 
  
X 
  
  
  
X 
  
  
X 
  
X 
  
X 
  
  
  
X 
Coagulation Panel 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urinalysis 
X 
  
X 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
5q SMA Genetic 
Testing (SMN1 and 
SMN2) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
Survival Motor Neuron 
(SMN) Testing 
[BLOOD] 
  
X 
  
  
  
  
  
  
  
  
X 
  
  
X 
X 
  
  
X 
Electrocardiogram 
(ECG) 
X 
  
X 
  
  
  
X 
  
  
X 
  
X 
  
  
X 
  
  
X 
Echocardiogram 
X 
  
  
  
  
  
X 
  
  
X 
  
X 
  
  
X 
  
  
X 
Study completion 
information 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 

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Period 
Screening 
Baselin
e 
Treatment 
Period 
Follow-up Period 
Visit Name 
Visi
t 1 
Visi
t 2 
Baselin
e Visit  
Da
y 1 
Da
y 2 
Da
y 3 
Wee
k 1 
Wee
k 2 
Wee
k 3 
Wee
k 4 
Wee
k 6 
Wee
k 8 
Wee
k 10 
Wee
k 12 
Wee
k 22 
Wee
k 32 
Wee
k 42 
Week 
52/EOS
1 
Days 
-45 
-0 
+15 
-21 
±2 
-1 
1 
2 
to 
2 
3 
to 
3 
8 ±2 
15 
±2 
22 
±2 
29 
±2 
43 
±2 
57 
±2 
71 
±2 
85 
±7 
155 
±7 
225 
±7 
295 
±14 
365 
±21 
Medical resource 
utilization 
  
  
  
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X Assessment to be recorded in the clinical database or received electronically from a vendor 
1 If discontinuation, all efforts should be made to complete the End of Study (EOS) assessments prior to study discontinuation. 
2 This assessment is conditional on availability 
3 
 
4 If applicable, reason for screen failure should be entered on the corresponding Case Report Form. Assessments and other eCRF pages must also be completed if data 
is available. 
5 SNAP is not performed at Screening Visit 2 if a SNAP score was obtained at Screening Visit 1 
6 Prophylactic prednisolone (or an equivalent) must be administered approximately 24 hours prior to OAV101 injection 
7 Prophylactic prednisolone (or an equivalent) may need to be continued beyond Week 8 Visit as described in Section 6.2 
8 Clinical and laboratory results must be consistent with institutional guidelines for lumbar puncture before proceeding with OAV101 IT administration. 
9 Refer to Section 6.7.3 for details of post-administration monitoring and optional assessments such as MRI or other safety assessments, based on Investigator 
discretion 
10 Exclusion criteria 11 and 12 must be confirmed for eligibility prior to OAV101 IT administration 
11 Participants will be hospitalized on Day 1 for inpatient OAV101 IT administration on Day 1, and in-patient observation will continue through Day 1, Day 2, and through 
part of   Day 3 (for at least 48 hours post-treatment).   
12 Vital signs to be performed pre-dose and post-dose as described in Section 8.4.5.4 
13 Refer to Section 8.4.5.1 for details 
14 S = assessment to be recorded in source documentation only 
15 C-SSRS is only to be performed in participants ≥ 7 years of age. For participants < 7 years old at Screening Visit 1 who will not turn 7 before the EOS Visit (Week 52), 
no C-SSRS assessment will be performed. For participants < 7 years old at Screening Visit 1 who will turn 7 before the EOS Visit (Week 52), C-SSRS assessments will 
commence at the visit following the participant's 7th birthday. 
16 Assessments may occur over more than 1 day within the visit window, but must not exceed 4 days 
17 Female participants of child bearing potential  
18 Hematology assessment at Day 2 should be performed locally; further, close monitoring of platelets should be performed locally as needed in the first two weeks 
following infusion. 

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8.1 
Screening 
Screening 
Written informed consent must be obtained prior to any screening procedures. Please refer to 
Section 7 for the Informed Consent procedures. After informed consent is collected, the 
participant must be registered in IRT, eligibility reviewed and, once eligible (all exclusion 
criteria must be confirmed at this point) study treatment can be pre-ordered. Assessments that 
confirm participant eligibility into the study will occur at Screening Visits 1 and 2 and at 
Baseline Visit (Table 8-1). The exact sequence of Screening assessments is at the discretion of 
the Site. It is recommended to obtain the anti-AAV9 antibody screening results first for timely 
completion of the eligibility assessment. 
For participants who have abnormal screening assessments that may be a temporary condition 
(e.g. viral illness, concomitant medication, or laboratory values, etc.) respective eligibility 
assessments can be repeated within the screening window up to two times; however, each case 
must be discussed and agreed with the Sponsor. Repeated assessments must be documented and 
eCRFs need to be completed for any additional visit. 
Participants who fail eligibility for a temporary condition exceeding the screening visit window 
will be considered screen failed and may be re-screened once. Re-screened participants must be 
re-consented and a new Participant number will be assigned (link to numbering section). All 
screening tests must be repeated as per inclusion/exclusion requirements and re-screening must 
be documented in the medical records. 
8.1.1 
Inclusion and exclusion criteria 
The Investigator must ensure that all participants being considered for the study meet 
the inclusion criteria and do not meet any exclusion criteria. A relevant record (e.g., checklist) 
must be stored with the source documentation at the study site. Deviation from any entry 
criterion excludes a participant from enrollment into the study. The Investigator or his/her 
deputy must promote compliance to inclusion and exclusion criteria for the duration of the study. 
8.1.2 
Information to be collected on screening failures 
Participants who sign an informed consent form and are subsequently found to be ineligible 
will be considered as screen failures. The reason for screen failure should be entered on the 
applicable CRF. 
The following eCRF pages must also be completed for screen failure participants if applicable 
and data is available: 
• Informed consent  
• Demography  
• Inclusion/Exclusion Criteria  
• SMA diagnosis 
• Assessments completed prior to screen failing 

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• Withdrawal of consent 
• Rescreen  
• Anti-AAV9 Antibody Testing (Blood)  
• 5q SMA Genetic Testing (SMN1 and SMN2) 
• AE page if seriousness criteria is Death 
No other data will be entered into the clinical database for participants who are screen failures, 
unless the participant experienced a serious adverse event during the screening phase (see SAE 
Section 10.1.3 for reporting details) or protocol-related adverse event. Data and samples 
collected from participants prior to screen failure may still be analyzed. 
8.1.3 
Prior medications 
Prior medications entered into the database will be coded using the WHO Drug Reference List, 
which employs the Anatomical Therapeutic Chemical (ATC) classification system. 
8.1.4 
Medical history and current medical conditions 
Relevant medical history, hospitalizations, and current medical conditions will be recorded on 
the eCRF. Where possible, diagnoses and not symptoms will be recorded. Any event or change 
in the participant's condition or health status occurring prior to informed consent will be 
reported in the Relevant medical history / Current medical conditions section of the eCRF. 
SMA HISTORY 
SMA history may include the following: 
• Type of SMN1 pathogenic variants on each allele (e.g., deletion, point mutation) 
• SMN2 gene copy number 
• Age at SMA symptom onset 
• Date of SMA diagnosis 
• Highest motor function achieved 
• Type and frequency of physical therapy 
• Number of hospitalizations for pneumonia with or without respiratory failure 
• Familial history of SMA, including parent carriers and affected sibling(s) 
• Prior SMA treatment, duration of treatment, and reason for discontinuation  
8.1.5 
Screening laboratory tests 
Laboratory testing performed during the Screening Period is described in Table 8-1. 
All laboratory results from Screening Visit 2 must be confirmed to be normal before proceeding 
with ordering drug in the system. 
8.1.6 
Virus serology 
The administration of an AAV vector has the risk of causing immune-mediated hepatotoxicity. 
For participants who have active or chronic Hepatitis B or Hepatitis C, or known history of or 

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Therapy for further details on what information must be recorded on the appropriate page of the 
eCRF. 
8.3 
Efficacy 
The primary endpoint in this study is safety. The secondary endpoint efficacy assessments, 
HFMSE and the RULM, are chosen based on their acceptability to health authorities, extensive 
validation and clinical and trial use, and proof of utility for efficacy assessment in other trials 
(Mercuri et al 2018b).
 
The secondary efficacy endpoints rely on data collected by trained and qualified site clinical 
evaluators (physical or occupational therapist, or national equivalent) administering HFMSE 
and RULM during the screening period, and over a 52-week period after OAV101 
administration. 
8.3.1 
Secondary efficacy assessments 
8.3.1.1 
HFMSE 
HFMSE was devised for use in children with SMA Type 2 and Type 3 to give objective 
information on motor ability and clinical progression (Glanzman et al 2011) and has been used 
in a double blinded clinical trial of Type 2 SMA to demonstrate efficacy of SMN-targeting 
therapy (Mercuri et al 2012) 
HFMSE is a SMA-specific 33-item assessment that is administered by clinical evaluators in a 
short period of time, requires minimal equipment, and is designed to factor in patient fatigue. 
Each motor skill item is scored on a 3-point Likert scale from 0 (no response) to 2 (full response), 
with a total score range of 0 to 66. A higher score indicates a higher ability level. 
HFMSE assessment will be administered by a qualified site clinical evaluator (CE) in 
accordance with the Assessment Schedule (Table 8-1) for all participants. A CE is defined as a 
physical or occupational therapist, or national equivalent, and holds a valid physical or 
occupational therapy license in the state in which they are practicing, or country equivalent if 
outside the United States. 
8.3.1.2 
RULM 
RULM is a validated, SMA-specific assessment that measures motor performance in the upper 
limbs from childhood through adulthood in ambulatory and never ambulatory individuals with 
SMA, and weaker individuals who have a floor effect or very low score on the Hammersmith 
Functional Motor Scale (HFMS) (Mazzone et al 2017). RULM administration is recommended 
for assessment of patients >2 years of age with the ability to sit by the SMArtCare-project 
(Pechmann et al 2019, Schorling et al 2020). 
The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 
2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item 
scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting 
poorer ability. RULM consists of upper limb performance items that are reflective of reachable 

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If participants cannot visit the site for protocol specified safety lab assessments, an alternative 
lab (local) collection site may be used. 
All local labs should be reported on the respective eCRF page. 
Clinically significant abnormalities must be recorded as either medical history/current medical 
conditions or adverse events as appropriate. 
8.4.1.1 
Hematology 
Hematology analysis will include a complete blood count with differential and platelet count. 
Samples will be collected and shipped in accordance with the laboratory manual provided by 
the central laboratory. Blood samples for hematology analysis will be collected as specified 
in Table 8-1. 
Hematology analysis will include the following at all trial visits: 
• Hematocrit 
• Hemoglobin 
• Mean corpuscular hemoglobin (MCH) 
• Mean corpuscular hemoglobin concentration (MCHC) 
• MCV 
• Platelets 
• Red blood cells 
• White blood cells 
• Differential (Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Bands) 
Transient decreases in platelet counts, some of which met the criteria for thrombocytopenia, 
were observed in OAV101 clinical studies with intravenous administration. In most cases, the 
lowest platelet value occurred the first week following OAV101 administration. Platelet counts 
should be obtained before OAV101 administration and should be closely monitored in the first 
two weeks following infusion and on a regular basis afterwards, weekly for the first month and 
every 
other 
week 
for 
the 
second 
and 
third 
months 
as 
specified 
in  
Table 8-1, until platelet counts return to baseline 
To monitor platelet counts, hematology analyses are required on Day 2 prior to discharge and 
will be performed as per investigational site standard procedures at the local laboratory. As 
determined by the Investigator, further hematology tests should be done in the first two weeks 
following OAV101 administration as per investigational site standard procedures at the local 
laboratory. Local labs should be entered on the respective eCRF page. Investigators will receive 
hematology results from all other study visits from the central laboratory. 
8.4.1.2 
Coagulation panel 
Coagulation testing including prothrombin time (PT), international normalized ratio (INR) and 
activated partial thromboplastin time (aPTT) will be measured at Screening Visit 2. 

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8.4.1.3 
Clinical chemistry 
Samples will be collected and shipped in accordance with the laboratory manual provided by 
the central laboratory. Blood samples for chemistry analysis will be collected as specified in the 
Assessment Schedule (Table 8-1). 
Clinical chemistry is recommended to be evaluated in the non-fasted state. 
If immediate/same-day chemistry analyses are required, as determined by Investigator, tests 
will be performed as per investigational site standard procedures at the local laboratory. Local 
labs should be recorded on the respective eCRF page. If liver aminotransferase elevations 
occur post OAV101 administration, the process outlined in Section 10.2.1 should be 
followed. 
Chemistry analysis will include the following analytes: 
• Albumin 
• Alkaline phosphatase (ALP) 
• ALT 
• AST 
• GGT 
• Lactate dehydrogenase (LDH) 
• Glutamate dehydrogenase 
• serum HCO3− (bicarbonate) 
• Calcium 
• Phosphorus 
• Chloride 
• Sodium 
• Potassium 
• Creatinine 
• Creatine kinase 
• Blood urea nitrogen 
• TBL (NOTE: If the total bilirubin concentration is increased above 1.5 times the upper 
limit of normal, the test should be repeated so that direct and indirect reacting bilirubin 
can be differentiated.) 
• Direct bilirubin (if TBL is >1.5 x ULN) 
• Indirect bilirubin (if TBL is >1.5 x ULN) 
• Glucose 
Residual serum (including from screen failures) may also be used towards the development of 
an in vitro test and/or a companion diagnostic assay. 

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8.4.1.4 
Troponin I 
Samples will be collected and shipped in accordance with the laboratory manual provided by 
the central laboratory. Blood samples for Troponin I will be collected as specified in the 
Assessment Schedule (Table 8-1). 
If immediate/same-day Troponin I analyses are required, as determined by Investigator, tests 
will be performed as per investigational site standard procedures at the local laboratory. Local 
labs should be recorded on the respective eCRF page. 
8.4.1.5 
Urinalysis 
Dipstick measurements for protein, blood, and WBC/leukocytes will be performed. If dipstick 
measurement results are abnormal, results will be sent to the central laboratory for microscopic 
evaluation in accordance with the Laboratory Manual. 
8.4.1.6 
Serum beta-human chorionic gonadotropin pregnancy test 
(Quantitative). 
Serum beta-human chorionic gonadotropin (Beta-hCG) testing (Quantitative) will be performed 
at Screening Visit 2. Serum Beta-hCG testing will be performed on females of childbearing 
potential (See Section 8.4.3). 
8.4.1.7 
Urine beta-human chorionic gonadotropin pregnancy test 
(Qualitative). 
All female participants who are sexually active or have reached menarche will have pregnancy 
testing. Additional pregnancy testing might be performed if requested by local 
requirements. The cultural differences as well as standard of care approaches across 
participating countries must be taken into account in order to appropriately manage 
contraception and pregnancy considerations. 
Urine human chorionic gonadotropin (hCG) dipstick testing will be performed on females of 
child-bearing potential. First-morning urine is the preferred specimen; however, any specimen 
is suitable for testing (See Section 8.4.3). Results of hCG dipstick testing will be captured on 
source documentation only. 
8.4.2 
Cardiac evaluations 
8.4.2.1 
Electrocardiogram 
This study is centrally evaluated and thus, full details of all procedures relating to the ECG 
collection and reporting will be contained in the technical manual which is provided to the site 
by the core laboratory. 
In the event that a clinically significant ECG abnormality is identified at the site (e.g., severe 
arrhythmia, conduction abnormality of QT interval corrected by Fridericia’s formula (QTcF) > 
500 ms), a copy of the assessment is sent to the core laboratory for expedited central review if 
applicable. The Investigator or a medically qualified person will repeat the ECG to confirm the 
diagnosis, and initiate further work-up as needed. If the participant is hemodynamically 

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potential, qualitative beta-human chorionic gonadotropin in urine will be performed at Day 1, 
Week 4, and at all subsequent visits during the trial (See Section 8.4.1.7). It is important that 
participants on Day 1 are instructed to perform the urine pregnancy test first and only if the test 
result is negative proceed with the administration of the study treatment. Note that a positive 
urine test should be confirmed with a serum pregnancy test. In case of a positive test, 
the participant must contact the investigator immediately. In this fashion, the pregnancy 
discussion will become an additional point at each visit, serving to increase compliance with 
contraception. 
Additional pregnancy testing may be performed if requested per local requirements. The 
cultural differences across participating countries need to be taken into account and it is 
acceptable to have both options simultaneously in the protocol to allow for cultural differences 
between participating countries. 
Urine human chorionic gonadotropin (hCG) dipstick testing will be performed on females of 
child-bearing potential. First-morning urine is the preferred specimen; however, any specimen 
is suitable for testing. If participants cannot visit the site to have urine pregnancy dipstick testing, 
participants can perform the urine pregnancy test at home and report the result to the site. A 
communication process should be established with the participant so that the Site is informed 
and can verify the pregnancy test results (e.g., following country specific measures). 
8.4.4 
Suicidal ideation and behavior assessment 
8.4.4.1 
C-SSRS 
The C-SSRS is a tool to assess suicidal ideation and behavior. C-SSRS should be completed as 
per the Assessment Schedule in Table 8-1 and at all unscheduled visits. Four constructs are 
measured: severity of ideation, intensity of ideation, behavior and lethality of actual suicide 
attempts. Binary (yes/no) data are collected for 10 categories, and composite endpoints based 
on the categories are followed over time to monitor participant safety (Posner et al 2011). It 
maps to the Columbia-Classification Algorithm for Suicide Assessment (C-CASA) and meets 
the criteria listed in the Food and Drug Administration (FDA) draft guidance for assessment of 
suicidality in clinical trials (FDA 2012). The C-SSRS will be used to monitor the participants 
throughout the study. 
The C-SSRS is only to be performed in participants ≥ 7 years of age and is completed by proxy 
(caregiver). For participants < 7 years old at Screening Visit 1 who will turn 7 before EOS Visit 
(Week 52), C-SSRS assessment will commence at the visit following the participants 7th 
birthday. 
The “baseline/screening” version of the C-SSRS assesses the lifetime suicidality, while the 
“since last visit” version assesses any new instances of suicidality. 
If, at any time after screening and/or baseline, the score is “yes” on items 'active suicidal 
ideation with some intent to act, without specific plan' or 'active suicidal ideation with specific 
plan and intent' of the suicidal ideation section of the C-SSRS or “yes” on any item of the 
suicidal behavior section, the participant must be referred to a mental health care professional 
for further assessment and/or treatment. The decision on whether prednisolone (or equivalent) 

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treatment should be discontinued or tapered is to be taken by the investigator in consultation 
with the mental health professional to whom the participant is referred. 
In addition, all life-threatening events must be reported as SAEs. For example, if a participant 
answers “yes” to one of the questions in the suicidal behavior section, an SAE must be reported 
if the event was life-threatening. All events of “Non-Suicidal Self-Injurious Behavior” 
(question also included in the suicidal behavior section) should be reported as AEs and assigned 
the appropriate severity grade. 
8.4.5 
Clinical safety evaluations 
8.4.5.1 
Neurological examination 
A complete neurological examination is performed according to the Assessment Schedule 
(Table 8-1), with attention to exam features and participant symptoms consistent with a sensory 
neuropathy. The neurological exam should include detailed, age-appropriate sensory testing 
(such as examination of proprioceptive, vibratory, tactile and pain sensation) at each visit. An 
age appropriate sensory exam is important for sensory neuropathy detection. 
Any clinically significant abnormal finding should be recorded as an AE in the eCRF. 
Further clinical evaluation of somatic sensory abnormalities will be conducted per local 
standard of care, including but not limited to nerve conduction studies such as sensory nerve 
action potential (SNAP) and other optional assessments (e.g, MRI) that the Investigator may 
deem necessary for the evaluation. 
8.4.5.2 
Sensory Nerve Action Potential (SNAP) 
Sensory nerve action potential (SNAP) is a conduction study commonly used to evaluate 
suspected peripheral neuropathies. The SNAP provides information on the sensory nerve axon 
and its pathway from the distal receptors in the skin to the dorsal root ganglia to evaluate the 
function, especially the ability of electrical conduction by the sensory nerves of human body. 
The SNAP represents the sum of single nerve fiber action potentials by electrically stimulating 
sensory fibers. 
SNAP will be performed as per local and institutional guidelines at Screening and in the case 
of sensory abnormalities in the neurological examination, and can be initiated based on the 
clinical judgement at any time during the study. Orthodromic or antidromic SNAPs are 
acceptable depending on the institutional protocol. Performance of sensory nerve action 
potentials 
(SNAPs) 
should 
comply 
with 
professional 
society 
standards 
(Stålberg et al 2019, AANEM (2020)). The SNAP will be scored as “Present” or “Absent” or 
"Unable to obtain". Results will be entered in the eCRF and as an adverse event if applicable. 
Pre-treatment: SNAP must be performed for all participants at Screening Visit 1. If the SNAP 
is scored as “Unable to obtain” at Screening Visit 1, then SNAP must be performed at Screening 
Visit 2. Bilateral radial and sural nerve SNAPs must each be obtained at least once at one of the 
two screening visits for trial eligibility. Rescheduling is warranted when any factor impedes the 
ability to obtain SNAP data. 

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If the SNAP is scored as “Absent” at any one of the pre-treatment visits, the clinician must 
assess whether the absent SNAP is supported by any clinically significant sensory abnormal 
finding(s) in the neurological examination. 
Post-treatment: Post-treatment, SNAP must be performed if there are sensory abnormalities 
in the neurological examination. A complete neurological examination is performed at visits 
specified in Table 8-1, with attention to exam features and participant symptoms consistent with 
a sensory neuropathy (refer to Section 8.4.5.1).  
Any participant with new post-treatment sensory symptoms with or without loss of a SNAP 
will receive a comprehensive assessment of the differential diagnosis. The differential diagnosis 
should include a careful assessment for sensory neuronopathy (sensory ganglionopathy). CSF 
testing and MRI imaging of brain, spinal cord, and dorsal root ganglia is encouraged. Sensory 
ganglionopathies are usually associated with diffuse SNAP abnormalities but may be patchy 
early, with upper limb involved before lower limb. 
8.4.5.3 
Physical examination 
Physical examinations will be conducted according to the Assessment Schedule (Table 8-1). 
The Baseline (Day -1) physical examination will be performed prior to OAV101 administration. 
A complete review of systems is performed at the time of each physical examination. Physical 
examinations will include each system: head, eyes, ears, nose and throat (HEENT), lungs/thorax, 
cardiovascular, abdomen, musculoskeletal, neurologic, dermatologic, lymphatic, and 
genitourinary. 
Physical examination data will be captured on source documentation only. 
Any clinically significant abnormal finding occurring after signing of the informed consent will 
be recorded as an AE. 
8.4.5.4 
Vital signs 
Vital sign parameters include blood pressure, respiratory rate, pulse, temperature, and pulse 
oximetry. 
Vital signs will be obtained at each visit. Vital signs on Day 1 (OAV101 administration) , with 
the exception of blood pressure, will be recorded pre-dose and then monitored every 15 (± 5) 
minutes for the first 1 hour, every 30 (± 10) minutes until 2 hours, every 2 hours (± 15 minutes) 
until 8 hours, and every 4 hours (± 30 minutes) until 24 hours. Blood pressure will be recorded 
pre-dose and every 8 hours through 24 hours. Patients must be kept in an appropriate setting for 
48 to 72 hours for closer monitoring as per study protocol. After discharge, vital signs will be 
monitored as specified in Table 8-1. Vitals should be measured according to the site's standard 
operating procedure. 
Any clinically significant abnormal finding occurring after signing of the informed consent will 
be recorded as an AE. 

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8.4.6 
Anthropometry 
8.4.6.1 
Body height (segmental tibial length) 
Direct measurement of recumbent length or height may be challenging in children and 
adolescents with physical disabilities due to joint contractures, muscular weakness, scoliosis, 
or poor cooperation. Since participants in the trial are never ambulatory, use the tibial length 
for 
segmental 
height 
assessment 
in 
all 
participants 
(Preedy VR 2012, Samson-Fang and Bell KL 2013, Mokhy et al 2020). 
Tibial 
length 
measurement does not require specialized equipment, is not impacted on by knee and ankle 
contractures and the landmarks are relatively easy to palpate. 
• Use a flexible tape measure that does not stretch. 
• Tibial length is the distance from the superomedial edge of the tibia to the inferior edge of 
the medial malleolus. 
• The measurement should be conducted with the child in a seated position facing the 
observer with the left ankle or calf resting on the right knee so that the medial aspect of 
the tibia faces upwards. Measurements are recorded in centimeters (cm). 
• The calculation should be checked by a different healthcare professional. 
Use the following equation for both males and females to estimate height in males and 
females who are ≥ 2 to ≤ 12 years of age (Stevenson Equation). 
• Height = (3.26 × TL) + 30.8 
• TL=Tibial length 
Use the following equations for males and females to estimate height in males and females 
who are > 12 years of age (Gauld Equation). 
• Males: Height = (2.758 × TL) + (1.717 × A) + 21.818 
• Females: Height = (2.771 × TL) + (1.457 × A) + 37.748 
• TL = Tibial length (cm) 
• A = age in years to one decimal place (e.g 5.3 years) 
8.4.6.2 
Body weight 
Weight measurement for all trial participants should be performed as follows: 
• Remove shoes and heavy clothes. Weights taken with shoes on will be considered invalid. 
A thin set of clothes or examination gown is permitted. 
• Disposable undergarments (e.g., diapers) should be dry. 
• All medical appliances must be removed (e.g., ankle foot orthosis; thoraco-lumbar-sacral 
orthosis) 
• Use appropriately calibrated digital scale 
• Values are recorded in kilograms (kg) to two decimal places (e.g., 15.25 kg). 
• Participants who cannot stand alone on the scale will be weighed with the assistance of an 
adult. In order to obtain the patient weight, the adult weight is subtracted from the total 
weight of the patient+adult. 

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8.4.6.3 
BMI 
BMI is a person’s weight in kilograms divided by the square of height in meters. BMI must be 
calculated using height derived as explained in Section 8.4.6.1, and the calculation should be 
checked by a different healthcare professional. 
Use the following equation: 
• BMI = W / H2 
• W = weight in kilograms (kg) to two decimal places (e.g. 15.25 kg) 
• H = height in meters (m) to two decimal places (e.g. 0.92 m) 
8.4.7 
Appropriateness of safety measurements 
Safety assessments such as AEs, clinical laboratory assessments, ECGs, and vital signs are 
standard for this indication/participant population. 
8.5 
Additional assessments 
8.5.1 
Clinical Outcome Assessments (COAs) 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, 
COA data may be collected remotely (e.g., web portal, telephone interviews) depending on 
local regulations, technical capabilities, and following any applicable training in the required 
process. 
Clinician Reported Outcomes (ClinRO) 
The impact of OAV101 on ClinROs will be assessed by the following measures in order to 
understand clinically meaningful aspects of motor improvements. 
• Hammersmith Functional Motor Scale Expanded (2019 version) (Section 8.3.1.1) 
• Revised Upper Limb Module (16-Dec-2014) (Section 8.3.1.2) 
• 
 
• 
 
• 
 
Data will be captured through the use of an electronic clinical outcome assessment 
(eCOA) device, as provided to sites by selected third‑party vendor. 
Observer Reported Outcomes (ObsRO) 
The impact of OAV101 on caregiver experience will be assessed by the following measure. 
• ACEND instrument Section 8.3.3.6) 
The participant's caregiver is to be provided with the electronic version of the ACEND 
instrument to be completed at the scheduled visit, in accordance with the Assessment Schedule 
(Table 8-1). Data is to be captured through the third-party vendor provided hand-held electronic 

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9.1.2 
Discontinuation from study 
Discontinuation from study is when the participant permanently stops any protocol-required 
assessments or follow-up, for any reason. 
Discontinuation could also occur if, in the judgement of the investigator, an SMA-disease 
modifying drug such as nusinersen or risdiplam is recommended for the benefit of the 
participant or has otherwise been taken. 
If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in the assessment table (refer to Section 8). Participants who 
discontinue or withdraw will be offered to enroll in a long-term follow-up study (up to 15 years) 
to monitor long-term safety and efficacy. 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits or fail to 
respond to any site attempts to contact them without stating an intention to discontinue from the 
study or withdraw consent (or exercise other participants' data privacy rights), the Investigator 
must show "due diligence" by documenting in the source documents steps taken to contact the 
participant, e.g., dates of telephone calls, registered letters, etc. A participant should not be 
considered as lost to follow-up until due diligence has been completed or until the end of the 
study. 
9.2 
Withdrawal of informed consent/Opposition to use 
data/biological samples 
Withdrawal of consent/opposition to use of data and/or biological samples occurs in countries 
where the legal justification to collect and process the data is consent and when a participant: 
• Explicitly requests to stop use of their data 
and 
• No longer wishes to receive study treatment prior to OAV101 administration 
and 
• Does not want any further visits or assessments (including further study-related contacts) 
This request should be per local regulations (e.g. in writing) and recorded in the source 
documentation. 
Withdrawal of consent impacts ability to further contact the participant, collect follow-up data 
(e.g. to respond to data queries) and potentially other country-specific restrictions. It is therefore 
very important to ensure accurate recording of withdrawal vs. discontinuation based on the 
protocol definition of these terms. 
In this situation, the Investigator should make a reasonable effort (e.g., telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/exercise data privacy rights and record this information. The investigator shall clearly 
document if the participant has withdrawn his/her consent for the use of data in addition to a 
study discontinuation. 

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No further assessments must be conducted, and the data that would have been collected at 
subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/exercise data/privacy rights should be made as detailed in the assessment table (refer 
to Section 8). 
Further details on withdrawal of consent or the exercise of participants’ data privacy rights are 
included in the corresponding informed consent form. 
9.3 
Study completion and post-study treatment 
Study completion is defined as when the last participant finishes their last study visit and any 
repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator or, in the event of an early study termination decision, the date 
of that decision. 
9.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. 
Reasons for early termination: 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the study 
• Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data 
• Discontinuation of study drug development 
• Regulatory Authority recommendation 
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a participant who discontinued from study treatment: The investigator may be informed of 
additional procedures to be followed in order to ensure that adequate consideration is given to 
the protection of the participant’s interests. The Investigator or sponsor depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. The 
Principal Investigator or designee will contact the study participant and/or the caregiver and 
provide instructions for returning to the Independent Treatment Site, or the Local Study Site, as 
appropriate. Every effort will be made to complete all end of study visit assessments for all 
treated study participants in the case of early study termination by the sponsor. 

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10 
Safety monitoring, reporting and committees 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event is any untoward medical occurrence (e.g., any unfavorable and unintended 
sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation 
participant after providing written informed consent for participation in the study. Therefore, 
an AE may or may not be temporally or causally associated with the use of a medicinal 
(investigational) product. 
The Investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the participant at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
participant during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 
Adverse events will be assessed as follows: 
1. Severity grade 
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e., progression of the study indication) the assessment of causality 
will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant 
3. Its duration (start and end dates or ongoing) 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken with study treatment 
6. Its outcome (i.e., recovery status or whether it was fatal) 
All adverse events must be treated appropriately. 

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Conditions that were already present at the time of informed consent should be recorded in 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued through the end of study visit. If prednisolone 
(or equivalent) treatment is required after the end of study visit (Week 52), AE monitoring will 
continue for 30 days after the last dose of prednisolone. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent (e.g., continuing at the end of the study), and assessment must be made at each visit 
(or more frequently, if necessary) of any changes in severity, the suspected relationship to the 
interventions required to treat it, and the outcome. 
Information about known adverse drug reactions for the investigational drug can be found in 
the Investigator's Brochure. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in participant 
with the underlying disease. Alert ranges for laboratory and other test abnormalities are included 
in Appendix 1, Section 16.1. 
On the basis of important identified and potential risks associated with OAV101, AESIs are 
determined and categorized as follows. These will be summarized based using Standardized 
MedDRA terminology:  
• Hepatotoxicity 
• Transient thrombocytopenia 
• Thrombotic microangiopathy 
• Cardiac adverse events 
• Dorsal root ganglia toxicity 
• New malignancies 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 

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Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2A Guidelines 1994). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g., defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” 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 dependency or abuse (please refer to the ICH-
E2A Guidelines 1994). 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. Any suspected transmission via a medicinal product of an 
infectious agent is also considered a serious adverse reaction. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and throughout the 52-week duration post study treatment must 
be reported to Novartis safety immediately, without undue delay, but under no circumstances 
later than within 24 hours of obtaining knowledge of the events (Note: If more stringent, local 
regulations regarding reporting timelines prevail). Detailed instructions regarding the 
submission process and requirements are to be found in the Investigator folder provided to each 
site. 
SAEs occurring after the participant has provided informed consent until the time the participant 
is deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 

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immediately, without undue delay, but under no circumstances later than within 24 hours of the 
Investigator receiving the follow-up information (Note: If more stringent, local regulations 
regarding reporting timelines prevail). An SAE occurring at a different time interval or 
otherwise considered completely unrelated to a previously reported one must be reported 
separately as a new event. 
If the SAE is not listed in the Reference Safety Information in the Investigator’s Brochure (IB) 
and is reported or assessed to be related to the study treatment, a Novartis Chief Medical Office 
and Patient Safety (CMO & PS) Department associate may urgently require further information 
from the investigator for health authority reporting. Novartis may need to issue an Investigator 
Notification to inform all Investigators involved in any study with the same study treatment that 
this SAE has been reported. 
Suspected unexpected serious adverse reactions (SUSARs) will be collected and reported to the 
competent authorities and relevant ethics committees in accordance with European Union (EU) 
Clinical Trial Regulation 536/2014 (if submitted under EU CTR) or Guidance 2011/C 172/01 
or as per national regulatory requirements in participating countries. 
Information about all SAEs is collected and recorded on the eSAE with paper backup Serious 
Adverse Event Report Form; all applicable sections of the form must be completed in order to 
provide a clinically thorough report. 
Any SAEs experienced after last follow-up visits should only be reported to Novartis Safety if 
the investigator suspects a causal relationship to study treatment, unless otherwise specified by 
local law/regulations. 
10.1.4 
Pregnancy reporting 
If a female participant becomes pregnant, the pregnancy consent form should be presented to 
the participant. The participant must be given adequate time to read, review and sign the 
pregnancy consent form. This consent form is necessary to allow the investigator to collect and 
report information regarding the pregnancy. To ensure participant safety, each pregnancy 
occurring after signing the informed consent must be reported to Novartis within 24 hours of 
learning of its occurrence. The pregnancy should be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications. Risks 
to the fetus of recombinant AAV gene therapy to the fetus are unknown. 
Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship of OAV101 to any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported. 
If a female partner of a male participant who took study treatment in this study becomes 
pregnant, pregnancy outcomes should be collected. Consent to report information regarding 
these pregnancy outcomes should be obtained from the mother. 
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery. 

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NOTE: Payment for all aspects of obstetrical care, child or related care will be the participant’s 
responsibility. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE and reported to 
safety only if associated with a SAE. For more information on AE and SAE definition and 
reporting requirements, please see the respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
OAV101, a standardized process for identification, monitoring and evaluation of liver events 
has to be followed. 
Please refer to Appendix 2, Section 16.2 for complete definitions of liver laboratory triggers. 
Once a participant is exposed to study treatment, every hepatotoxicity event defined in 
Section 16.2 should be followed up by the Investigator or designated personnel at the trial site, 
as summarized below. Additional details on actions required in case of liver events are outlined 
in Table 16-1 and Table 16-2. 
If elevated, repeat liver chemistry tests (i.e., ALT, AST, total bilrubin (TBL), prothrombin 
time/international (PT/INR), ALP, and GGT) will be performed within 48-72 hours to confirm 
elevation. These liver chemistry repeats will be performed at a local laboratory to monitor the 
safety of the participant. Any local liver chemistry tests should have results recorded on the 
appropriate CRF. 
If the initial elevation is confirmed, the follow-up requirements include (refer to Table 16-1 and 
Table 16-2): 
• Hospitalization of the participant, if appropriate 
• Causality assessment of the liver event 
• Thorough investigation and follow-up of the liver event, which may include, based on 
Investigator’s discretion: serology tests, laboratory tests for other causes of hepatitis, 
including viral hepatitis, imaging such as abdominal ultrasound/elastography and 
pathology assessments 
• Obtaining a more detailed history of signs and symptoms and prior or concurrent diseases. 
• Obtaining a history of concomitant drug use, including nonprescription medications (e.g., 
acetaminophen); and herbal and dietary supplement preparations 
• Exclusion of underlying liver disease 

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Code of Federal Regulations (CFR) Part 11 requirements, Investigator site staff will not be 
given access to the EDC system until they have been trained. Automatic validation programs 
check for data discrepancies in the eCRFs, allow modification and/or verification of the entered 
data by the Investigator staff. 
The Investigator/designee is responsible for assuring that the data (recorded on CRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (or designated Clinical Research Organization (CRO)) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated investigator 
site staff are required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and made available for data analysis. Any changes to 
the database after that time can only be made after written agreement by Novartis development 
management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an Investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e., electronic CRFs 
(eCRFs)) with the Investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of participant records, the 
accuracy of data capture / data entry, the adherence to the protocol and to GCP, the progress of 
enrollment, and to ensure that study treatment is being stored, dispensed, and accounted for 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits. Continuous remote monitoring of each site’s data may be performed by the 
CRAs. 

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The Investigator must maintain source documents for each participant in the study, consisting 
of case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
participant's file. The Investigator must also keep the original informed consent form signed by 
the participant (a signed copy is given to the participant). 
The Investigator must give to the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis monitoring standards require 
full verification for the presence of informed consent, adherence to the inclusion/exclusion 
criteria, documentation of SAEs, and of data that will be used for all primary variables. 
Additional checks of the consistency of the source data with the eCRFs are performed according 
to the study-specific monitoring plan. No information in source documents about the identity 
of the participants will be disclosed. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novartis. No records may be transferred to 
another location or party without written notification to Novartis. 
12 
Data analysis and statistical methods 
12.1 
Analysis sets 
The full analysis set (FAS) is comprised of all participants who are enrolled in this study and 
received OAV101 through IT administration. The safety analysis set (SAF) is defined as the 
same as the FAS, therefore all the efficacy and safety analyses will be conducted using FAS. 
12.2 
Participant demographics and other baseline characteristics 
Demographic and other baseline data including disease characteristics will be listed and 
summarized descriptively by strata and overall for the FAS. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented. For selected parameters, 
25th and 75th percentiles will also be presented. 
Relevant medical histories and current medical conditions at baseline will be summarized by 
system organ class and preferred term by strata and overall for the FAS. 
12.3 
Treatments 
The FAS will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 25th and 
75th percentiles, minimum, and maximum will be presented. 
The details pertaining to the administration of study treatment will be summarized by means of 
descriptive statistics using the FAS. 

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Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be summarized according to the ATC classification system by strata and 
overall. 
12.4 
Analysis supporting primary objectives 
The primary objective of the study is described in Table 2-1. Efficacy analyses will use the FAS. 
A final analysis will be performed after all participants have completed Week 52 or 
discontinued prior to Week 52. 
12.4.1 
Definition of primary endpoint(s) 
The primary endpoint includes the number and percentage of participants reporting AEs, related 
AEs, SAEs, and AESIs. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The number and percentage of participants reporting AEs, related AEs, SAEs and AESIs will 
be summarized by strata and overall in the safety analysis set. Summaries will also be provided 
by MedDRA system organ class and preferred terms. 
No hypothesis testing will be performed. 
12.4.3 
Handling of intercurrent events of primary estimand 
All intercurrent events including receiving prohibited concomitant medications will be handled 
by treatment policy strategy, namely, all AEs, related AEs, SAEs (including death) and AESIs 
observed while/after receiving prohibited concomitant medications will be reported. 
12.4.4 
Handling of missing values not related to intercurrent event 
Not applicable. 
12.4.5 
Sensitivity analyses 
Given the descriptive nature of the summary of primary safety endpoints, no sensitivity analyses 
will be performed. 
12.4.6 
Supplementary analysis 
No supplementary analysis will be performed. 
12.5 
Analysis supporting secondary objectives 
The secondary objective of the study is described in Table 2-1 . Efficacy analyses will use the 
FAS. 
A final analysis will be performed after all participants have completed Week 52 or 
discontinued prior to Week 52. 

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13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, participant recruitment procedures (e.g., 
advertisements) and any other written information to be provided to participants. Prior to study 
start, the investigator is required to sign a protocol signature page confirming his/her agreement 
to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol and to give access to all relevant data and records to Novartis 
monitors, auditors, Novartis Quality Assurance representatives, designated agents of Novartis, 
IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site is 
requested by a regulatory authority, the investigator must inform Novartis immediately that this 
request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in the European Union Drug Regulating Authorities Clinical Trials Database 
(EudraCT). In addition, after study completion (defined as last participant last visit) and 
finalization of the study report the results of this trial will be submitted for publication and 
posted in a publicly accessible database of clinical trial results, such as the Novartis clinical trial 

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results website and all required Health Authority websites (e.g., Clinicaltrials.gov, EudraCT 
etc.). 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial Investigator 
meetings. 
Any data analysis carried out independently by the Investigator should be submitted to Novartis 
before publication or presentation. 
Summary results of primary and secondary endpoints will be disclosed based upon global Last 
Participant Last Visit (LPLV) date, since multinational studies are locked and reported based 
upon the global LPLV. 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis processes. 
13.5 
Participant Engagement 
The following participant engagement initiatives are included in this study and will be provided, 
as available, for distribution to study participants at the timepoints indicated. If compliance is 
impacted by cultural norms or local laws and regulations, sites may discuss modifications to 
these requirements with Novartis. 
• Thank you letter 
• Plain language trial summary - after CSR publication 
14 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 

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Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and Health Authorities, where required, it cannot be implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 

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15 
References 
References are available upon request 
AANEM Professional Practice Committee (2020) Establishing standards for acceptable 
waveforms in nerve conduction studies. Muscle&Nerve;61:280-7.  
Annoussamy M, Seferian AM, Daron A, et al (2021) Natural history of Type 2 and 3 spinal 
muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol; 8(2):359-73. 
Aragon-Gawinska K, Daron A, Ulinici A, et al (2020) Sitting in patients with spinal muscular 
atrophy type 1 treated with nusinersen. Dev Med Child Neurol; 62:310-4. 
Bernal S, Alías L, Barceló MJ, et al (2010) The c.859G>C variant in the SMN2 gene is 
associated with types II and III SMA and originates from a common ancestor. J Med Genet; 
47:640-2. 
Calucho M, Bernal S, Alías L, et al (2018) Correlation between SMA type and SMN2 copy 
number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 
reported cases. Neuromuscul Disord; 28:208-15. 
Chabanon A, Seferian AM, Daron A, et al (2018) Prospective and longitudinal natural history 
study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA 
study.Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history 
study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA 
study. PLoS One; 13(7):e0201004.  
European Commission (2017) Ethical considerations for clinical trials on medicinal products 
conducted with minors (Internet) Available from: < health.ec.europa.eu/system/files/2018-
02/2017_09_18_ethical_consid_ct_with_minors_0.pdf> (Accessed 03-Apr-2023) 
EMA (2001) Note for guidance on clinical investigation of medicinal products in the 
paediatric population (Internet) Available from:<//ema.europa.eu/en/documents/scientific-
guideline/international-conference-harmonisation-technical-requirements-registration-
pharmaceuticals-human-use_en-1.pdf> (Accessed 23-Feb-2022). 
FDA (2009)  Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation (Internet) Available from: <//fda.gov/ media/116737/download> (Accessed 30-
Mar-2023). 
FDA (2012) Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment 
of Occurrence in Clinical Trials (Internet) Available from:<//.fda.gov/regulatory-
information/search-fda-guidance-documents/guidance-industry-suicidal-ideation-and-
behavior-prospective-assessment-occurrence-clinical-trials> (Accessed 05-Dec-2021). 
Fleming S, Thompson M, Stevens R, et al (2011) Normal ranges of heart rate and respiratory 
rate in children from birth to 18 years of age: a systematic review of observational studies. 
Lancet; 377:1011-8. 
Flynn JT, Kaelber DC, Baker-Smith CM, et al (2017) Subcommittee on Screening and 
Management of High Blood Pressure in Children. Clinical Practice Guideline for Screening 

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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs 
Clinically relevant laboratory abnormalities 
Age-appropriate, normal laboratory values and clinical measurements should be used in 
pediatric population. Laboratory tests are commonly interpreted in relation to established 
reference intervals. These limits serve to differentiate between normal and pathological findings, 
and to gauge the severity of any abnormal increases or decreases. As far as laboratory 
parameters are known to characteristically vary with age, pediatric test results are usually 
interpreted in relation to these physiological dynamics. Reference intervals for pediatric patients 
have been calculated by partitioning data from a healthy reference population into age groups, 
so that the corresponding subset-specific percentiles would form step functions of age 
(Hirschmann et al 2017). 
The full list of clinically relevant laboratory abnormalities will be included in the CSR and 
detailed summary methods will be specified in the Statistical Analysis Plan. 
Vital signs 
Within vital signs data, height and weight are commonly collected along with heart rate, 
respiratory rate, and blood pressure. The exam and vital sign data can be interpreted only with 
a thorough understanding of normal values. In pediatrics, normal respiratory rate, heart rate, 
and blood pressure have age-specific norms (Flynn et al 2017, Fleming et al 2011). 
The full list of clinically relevant vital signs will be included in the CSR and detailed summary 
methods will be specified in the Statistical Analysis Plan. 

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16.2 
Appendix 2: Liver laboratory triggers & follow-up monitoring 
requirements 
16.2.1 
Liver laboratory triggers 
Liver laboratory triggers which require follow-up monitoring include: 
• ALT > 3 × ULN 
• TBL > 1.5 × ULN (in the absence of known Gilbert’s syndrome) 
• Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and TBL > 2 × ULN 
[mainly conjugated (direct) fraction] without notable increase in ALP to > 2 × ULN) 
16.2.2 
Follow-up requirements for liver laboratory triggers ALT and AST, with 
and without TBL 
Table 16-1 
Follow-up requirements for liver laboratory triggers – ALT and AST, 
with and without TBL 
ALT 
TBL 
Liver Symptoms 
Actions and Follow-up 
Monitoring 
ALT > 3 x ULN 
● Normal 
● For participants with 
Gilbert’s syndrome: No 
change in baseline TBL 
None 
● Review compliance with 
immunomodulatory therapy 
(Section 6.2) 
● Measure ALT, AST, 
TBL, fractionated bilirubin 
(direct and indirect), INR, 
and GLDH within 48- 72 
hours. 
● Follow-up for 
symptoms. 
ALT > 5 x ULN 
● Normal 
● For participants with 
Gilbert’s syndrome: No 
change in baseline TBL 
With or without 
symptoms 
● Review compliance with 
immunomodulatory therapy 
(Section 6.2.2) 
● Measure ALT, AST, 
TBL, fractionated bilirubin 
(direct and indirect), INR, 
albumin, creatine kinase 
(CK), and GLDH within 48 - 
72 hours of test results. 
ALT or AST > 3 x ULN 
● TBL > 2 x ULN (or 
INR > 1.5) 
● For participants with 
Gilbert’s syndrome: 
Doubling of direct 
bilirubin 
With or without 
symptoms 

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ALT 
TBL 
Liver Symptoms 
Actions and Follow-up 
Monitoring 
ALT > 3 x ULN 
● Normal or elevated 
Severe fatigue, nausea, 
vomiting, and/or right 
upper quadrant pain 
● Follow-up for 
symptoms. 
● Initiate close monitoring 
(hospitalization when 
appropriate) and workup for 
competing etiologiesa 
● Exclude underlying liver 
disease 
● Obtain detailed history 
of concomitant medications 
(e.g acetaminophen) 
● Consult 
pediatric gastroenterologistb 
a Work-up for competing etiologies may include (but not limited to) viral hepatitis panel (IgM anti-hepatitis A 
virus (HAV); hepatitis B virus surface antigen (HBsAg), IgM and total anti-hepatitis B core (HBc), hepatitis B 
virus (HBV) DNA, hepatitis C virus (HCV) ribonucleic acid (RNA), anti-HCV, Immunoglobulin M (IgM) & 
immunoglobulin G (IgG), hepatitis E virus (HEV) RNA, anti-HEV IgM and IgG), viral panel (CMV IgM and IgG, 
Epstein Barr virus (EBV) IgM and IgG, herpes simplex virus (HSV) IgG and Type 1 and 2 DNA), autoimmune 
hepatitis (anti-nuclear antibodies titer and pattern, anti-smooth muscle antibody) 
bConsider appropriate imaging and liver biopsy in consultation with a pediatric gastroenterologist 
16.2.3 
Follow-up requirements for liver laboratory triggers - isolated 
hyperbilirubinemia 
Table 16-2 
Follow-up requirements for liver laboratory triggers - isolated 
hyperbilirubinemia 
Criteria Total Bilirubin (isolated) 
Actions required 
Follow-up monitoring 
>1.5 – 3.0 x ULN 
● Repeat LFTs within 72 hours of 
test results 
● Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline 
> 3 - 10 x ULN (in the absence of 
known Gilbert's syndrome) 
● Repeat LFT within 72 hours of 
test results 
● Hospitalize if clinically 
appropriate 
● Establish causality 
● Record the AE and contributing 
factors (e.g. 
concomitant medications, medical 
history, laboratory results) in the 
appropriate CRF 
● Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline (ALT, AST, TBL, albumin, 
PT/INR) 
● Test for hemolysis (e.g. 
reticulocytes, haptoglobin, 
unconjugated [indirect] bilirubin) 
> 10 x ULN 
● Hospitalize the participant 
● Establish causality 
● Record the AE and contributing 
factors(e.g. 
concomitant medications, medical 
history, laboratory results) in the 
appropriate CRF 
● ALT, AST, TBL, Alb, PT/INR, 
until resolution (frequency at 
Investigator discretion) 
LFT(s) = liver function tests based on Investigator’s discretion; investigation(s) for contributing factors for the 
liver event can include: Serology tests, imaging and pathology assessments, pediatric gastroenterologist's or 

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Criteria Total Bilirubin (isolated) 
Actions required 
Follow-up monitoring 
hepatologist’s consultancy; obtaining more detailed history of symptoms and prior or concurrent diseases, 
history of concomitant drug use, exclusion of underlying liver disease. 

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16.3 
Appendix 3: Specific Renal Alert Criteria and Actions and Event 
Follow-up 
Not applicable