Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients With Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant
Phase: PHASE2
Conditions: Parkinson's Disease
Sponsor: Genzyme, a Sanofi Company

 
 
 
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affiliated companies). The use of such confidential information must be restricted to the recipient for the agreed purpose and must not be 
disclosed, published or otherwise communicated to any unauthorized persons, for any reason, in any form whatsoever without the prior written 
consent of Sanofi (or the concerned affiliated company); ‘affiliated company’ means any corporation, partnership or other entity which at the date 
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direct or indirect ownership of more than 50% of the capital stock or the voting rights in such corporation, partnership or other entity 
 
According to template: QSD-003152 VERSION N°3.0 (04-FEB-2016) 
Page 1 
 
AMENDED CLINICAL TRIAL PROTOCOL 06 
COMPOUND: GZ/SAR402671  
Multicenter, randomized, double-blind, placebo-controlled study to assess the 
efficacy, safety, pharmacokinetics, and pharmacodynamics of GZ/SAR402671 in 
patients with early-stage Parkinson’s disease carrying a GBA mutation or other 
prespecified variant 
Multicenter pharmacOkinetics and interVEntional Study in Parkinson’s Disease  
STUDY NUMBER: ACT14820 
STUDY NAME: MOVES-PD 
Version number: 
1  
EudraCT number: 
2016-000657-12 
NCT: 
NCT02906020 
IND number: 
129426 
WHO universal trial number: 
U1111-1180-6918 
Date:09-Feb-2021  
Total number of pages: 
198 

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Page 2 
NAMES AND ADDRESSES OF 
COORDINATING 
INVESTIGATOR 
 
Name: 
Address: 
 
 
Tel: 
Fax: 
E-mail: 
 
 
MONITORING TEAM’S 
REPRESENTATIVE 
 
Name: 
Address: 
 
 
 
Tel: 
Fax: 
E-mail: 
 
 
SPONSOR 
 
Company: 
Address: 
 
 
 
 
Genzyme Corporation 
50 Binney Street 
Cambridge, MA 02142 
USA 
 
OTHER EMERGENCY 
TELEPHONE NUMBERS 
 
 
 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES  
DOCUMENT HISTORY 
 
Document 
Country/ 
countries 
impacted by 
amendment 
Date, version 
Amended Clinical Trial Protocol 06 (Global) 
Amended Clinical Trial Protocol 05 (Global) 
All 
All 
09-Feb-2021, Version 01 (electronic 6.0) 
03-Sep-2020, version 01 (electronic 5.0) 
Amended Clinical Trial Protocol 04 (Global) 
All 
21-May-2020, version 01 (electronic 4.0) 
Amended Clinical Trial Protocol 03 (Global) 
All 
20-Jul-2018, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 04 (JP) 
Japan only 
06-Jun-2017, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 03 (ISR) 
Israel only 
06-Jun-2017, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 02 (Global) 
All 
06-Jun-2017, version 01 (electronic 1.0) 
Protocol Amendment 05 (Global) 
All 
06-Jun-2017, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 03 (JP) 
Japan only 
01-Feb-2017, version 01 (electronic 4.0) 
Protocol Amendment 04 (JP) 
Japan only 
01-Feb-2017, version 01 (electronic 4.0) 
Amended Clinical Trial Protocol 02 (ISR) 
Israel only 
08-Dec-2016, version 01 (electronic 2.0) 
Amended Clinical Trial Protocol 02 (JP) 
Japan only 
08-Dec-2016, version 01 (electronic 3.0) 
Amended Clinical Trial Protocol 01 (Global) 
All 
08-Dec-2016, version 01 (electronic 1.0) 
Protocol Amendment 03 (Global) 
All 
08-Dec-2016, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 02 (ISR) 
Israel only 
15-Aug-2016, version 01 (electronic 1.0) 
Protocol Amendment 02 (ISR) 
Israel only 
15-Aug-2016, version 01 (electronic 1.0) 
Amended Clinical Trial Protocol 01 (JP) 
Japan only 
15-Nov-2016, version 01 (electronic 1.0) 
Protocol Amendment 01 (JP) 
Japan only 
15-Nov-2016, version 01 (electronic 2.0) 
Clinical Trial Protocol 
 
30-Jun-2016, version 01 (electronic 1.0) 

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Amended clinical trial protocol 06 (09 February 2021) 
This amended protocol (amendment 06) is considered to be non substantial based on the criteria 
set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The protocol is being amended to add MDS-UPDRS and BDI-II assessments at Visit 16 (Follow-
up visit) and to increase the wash-out period before Visit 16 while allowing more flexibility on the 
visit window. This will help to better document the course of the disease after study treatment 
discontinuation.   
Protocol amendment summary of changes table 
Section # and Name 
Description of 
Change 
Brief Rationale 
Clinical trial summary: Study design, Assessment schedule, 
Duration of the study; Section 1.2 Graphical study design for part 
2; Section 1.3.3, Part 2: study schedule of assessments (Periods 3 
and 4); Section 6.1 Description of the study; Section 6.2.1 
Duration of study participation for each patient; Section 8.3.2 
Randomization code breaking during Part 2; Section 9.1.2 
Treatment phase; Section 9.3.3.3 Vital signs; Section 9.3.3.4 
Physical examination, Section 9.3.3.5 Neurological examination; 
Section 9.3.3.6 Ophthalmological examination; Section 10.1.2 Part 
2 : Treatment phase; Section 10.1.2.11 Eight week follow-up visit; 
Section 10.3.3 List of criteria for permanent discontinuation; 
Section 10.3.4 Handling of patients after permanent 
discontinuation; Section 10.3.5 Procedure and consequence for 
patient withdrawal from study;  
 
 
 
 
Appendix U Protocol amendment history 
Sections updated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised to reflect current 
updates 
 
Week 214 (Visit 16) changed 
to Week 216 with visit window 
increased to ± 2 weeks 
instead of ± 1 week. MDS-
UPDRS and BDI-II added at 
Visit 16. 
 
 
 
 
 
 
 
 
 
 
Administrative changes  
 
 
 
 

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CLINICAL TRIAL SUMMARY 
COMPOUND: GZ/SAR402671 
STUDY No.: ACT14820 
STUDY NAME: MOVES-PD 
TITLE 
Multicenter, randomized, double-blind, placebo-controlled study to 
assess the efficacy, safety, pharmacokinetics, and 
pharmacodynamics of GZ/SAR402671 in patients with early-stage 
Parkinson’s disease carrying a GBA mutation or other prespecified 
variant. 
INVESTIGATOR/TRIAL LOCATION 
International, multicenter trial. 
PHASE OF DEVELOPMENT 
Phase 2 
STUDY OBJECTIVES  
 
Part 1:  Dose escalation phase 
Primary objective: 
• 
To determine the safety and tolerability of 4, 8, and 15 mg 
of GZ/SAR402671, as compared to placebo, when 
administered orally daily for 4 weeks in early-stage 
Parkinson’s disease (PD) patients carrying a 
glucocerebrosidase gene (GBA) mutation or other pre-
specified sequence variants (from now on both mutation 
types are referred to as ‘GBA mutation’). This will allow 
selection of the dose for the second part of this study (this 
does not apply to Japanese patients). 
 
Secondary objectives: 
• 
To assess the pharmacokinetic (PK) profile of daily oral 
dosing of GZ/SAR402671 in plasma when administered at 
doses of 4, 8, or 15 mg over a 4-week period in early-stage 
PD patients carrying a GBA mutation. 
• 
To assess the exposure of GZ/SAR402671 in cerebrospinal 
fluid (CSF) when administered at doses of 4, 8, or 15 mg 
over a 4-week period in early-stage PD patients carrying a 
GBA mutation. 
 
Exploratory Objectives: 
• 
To assess the pharmacodynamic response of daily oral 
dosing of GZ/SAR402671 in plasma and CSF when 
administered at doses of 4, 8 or 15 mg over a 4-week 
period, as measured by glucosylceramide (GL-1) in 
early-stage PD patients carrying a GBA mutation. 
• 
To explore the effect of GZ/SAR402671 on scores from 
selected scales and questionnaires which will be used in 
this study over an 8-week period in early stage PD patients 
carrying a GBA mutation. 
 
Part 2: Treatment phase 
Primary objective: 
• 
To determine the efficacy of GZ/SAR402671 in patients 
with early-stage PD carrying a GBA mutation when 

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administered orally daily at the dose selected in Part 1, over 
a 52-week period, as compared to placebo. 
 
Secondary objectives: 
• 
To demonstrate the overall safety and tolerability of 
GZ/SAR402671 administered orally daily for 52 weeks in 
early-stage PD patients carrying a GBA mutation as 
compared to placebo. 
• 
To assess the pharmacodynamic response to daily oral 
dosing of GZ/SAR402671 in plasma and CSF as measured 
by GL-1 in early-stage PD patients carrying a GBA mutation 
over a 52-week period. 
 
Exploratory objectives: 
• 
To explore the effect of GZ/SAR402671 on scores from 
selected scales and questionnaires which will be used in 
this study. Of note, for patients receiving levodopa or other 
PD medication, assessment of scales and questionnaires 
will be performed during the OFF state (ie, no PD 
medication may be taken for at least 12 hours prior to the 
efficacy assessments) except for the Hoehn & Yahr (H&Y) 
scale which will be completed in "ON" state only at baseline 
visit (see inclusion criteria I 05). 
• 
To assess the effect of GZ/SAR402671 on neurologic 
functional status via functional neuroimaging over a 
52-week period. 
• 
To assess the PK profile of GZ/SAR402671 in plasma and 
CSF of early-stage PD patients carrying a GBA mutation. 
• 
To evaluate the pharmacodynamic response to 
GZ/SAR402671 in plasma and CSF as measured by 
glucosylsphingosine (lyso-GL-1) in early-stage PD patients 
carrying a GBA mutation. 
• 
To explore the effect of GZ/SAR402671 on CSF biomarkers 
related to PD or neurodegeneration, including total 
α-synuclein (α-Syn), neurofilament light chain (NFL), tau, 
phospho-tau, as well as beta-amyloid (1-40 and 1-42). 
• 
To develop a Parkinson’s disease progression model in 
early-stage PD patients carrying a GBA mutation. 
• 
To assess the long-term safety and efficacy of 
GZ/SAR402671 over a 156-week period. 
STUDY DESIGN 
This is a two-part, multicenter, multiple-country, randomized, 
double-blinded, placebo-controlled study in early-stage PD patients 
carrying a GBA mutation. The study will be divided into 2 consecutive 
parts. Part 1 will be a randomized, double-blinded, placebo-controlled 
dose escalation study, utilizing a sequential cohort design. Part 1 will 
allow selection of the dose of GZ/SAR402671 for Part 2, a 
randomized, double-blind, placebo-controlled, 2-arm study of the 
efficacy and safety of GZ/SAR402671. Part 1 will be conducted only 
in selected sites (approximately 20 sites [including 4 Japanese sites]); 
Part 2 will be conducted at multiple sites (approximately 50). Part 2 
will start after the appropriate dose for Part 2 is selected in Part 1. 

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In Part 1, during the screening/baseline period, from Day -60 to 
Day -1, patients will provide informed consent and undergo screening 
assessments to determine trial eligibility and undergo baseline 
measurements. If all eligibility criteria are met, patients will enter the 
study. Part 1 will determine the safety and tolerability of 
GZ/SAR402671 at 4, 8, and 15 mg in early-stage PD patients 
carrying a GBA mutation by using a dose escalation scheme. There 
will be 3 sequential cohorts that will be placebo-controlled: 
• 
Cohort 1: 4 patients on GZ/SAR402671 4 mg and 1 patient 
on placebo. 
• 
Cohort 2: 4 patients on GZ/SAR402671 8 mg and 1 patient 
on placebo. 
• 
Cohort 3: 4 patients on GZ/SAR402671 15 mg and 
1 patient on placebo. 
No additional dose escalation of GZ/SAR402671 will occur above the 
highest proposed dose of 15 mg. All patients must complete the first 
4-week course of therapy with subsequent data review, 
demonstrating safety/tolerability before dose escalation to the next 
higher level can occur. Patients will continue to be dosed daily and 
will be followed every 4 weeks until the completion of Part 1, allowing 
for additional safety and other exploratory endpoints to be collected. 
Each cohort will have a 4:1 randomization ratio, and the total sample 
size will be approximately 15 patients (including 12 on 
GZ/SAR402671 and 3 on placebo). In Japan, each cohort will have a 
3:1 randomization ratio, and the total sample size will be 
approximately 12 Japanese patients (including 9 on GZ/SAR402671 
and 3 on placebo). Therefore, the total sample size in Part 1 will be 
approximately 27 patients. 
If a serious adverse event (SAE) or ≥Grade 3 adverse event (AE, 
National Cancer Institute (NCI), Common Terminology Criteria for 
Adverse Events [CTCAE] Version 4.03) that is considered by the 
Investigator to be related to GZ/SAR402671 and not to underlying 
disease or concomitant medication is observed, the case will be 
communicated to the internal review committee and a decision should 
be reached regarding escalation to the next dose with 
GZ/SAR402671. If 2 patients receiving GZ/SAR402671 within the 
same cohort develop the same SAE or AE (≥Grade 3), dosing within 
the cohort will be stopped. After stopping, the internal review 
committee will review the data and provide recommendations on how 
to proceed. In addition, SAE/adverse events of special interest 
(AESIs) will be communicated to the Data Monitoring Committee 
(DMC). 
At the end of 4 weeks of treatment during the dose escalation part, 
patients in each cohort will have a lumbar puncture (LP); CSF 
exposure of GZ/SAR402671 will be measured at 2 time points in 
Part 1: at pretreatment and Week 4. If there is no CSF exposure at 
the highest dose level, the study will be stopped. 
In Part 2, the GZ/SAR402671 dose will be the highest dose 
determined to be safe and well tolerated in Part 1. If patients from 
Part 1 continue to meet eligibility requirements, they may enroll in 
Part 2, but re-randomization will be required; furthermore, they will 
have to sign another informed consent form. All screening 
assessments will need to be repeated, except for the genetic 

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screening, magnetic resonance imaging (MRI), LP, and ioflupane 
I-123 injection DaTSCAN (DAT scan), to confirm eligibility of patients 
from Part 1 to enroll in Part 2. 
In Part 2, eligible patients will be stratified based on use of 
levodopa/PD medication (yes/no), cognitive function (Montreal 
Cognitive Assessment [MoCA]) score <26 [yes/no]), and severe GBA 
mutation (yes/no). Patients will be randomized in a 1:1 ratio to receive 
GZ/SAR402671 or placebo for 52 weeks. 
Part 2 will include 4 main periods: the up to 60-day screening period 
(Period 1), the 52-week blinded treatment period (Period 2), the 
156-week duration long-term follow-up (LTFU) period (Period 3), and 
the 8-week post-treatment observation period (Period 4).  
All patients who continue to meet inclusion criteria I 06, I 07, I 08, and 
I 09 and none of the exclusion criteria (exclusion criteria E 02, E 03, 
E 05, and E 06 will not need to be rechecked) at Week 52 will be 
eligible to receive GZ/SAR402671 treatment during the LTFU period 
(Period 3).   
STUDY POPULATION  
 
Main selection criteria: 
Inclusion criteria: 
I 01. 
Male or female subjects with a diagnosis of PD (with at least 
two of the following signs: resting tremor, postural instability, 
akinesia/hypokinesia, and muscle rigidity) and who are 
heterozygous carriers of a GBA mutation.  
Note: If the patient has a GBA mutation that is not on the 
list, a consult will always be required to determine the 
eligibility of the patient. 
OR  
I 02. 
Patients carrying known sequence variants associated with 
GBA-PD, in addition to having a diagnosis of PD (with at 
least 2 of the following signs: resting tremor, postural 
instability, akinesia/hypokinesia or muscle rigidity), must 
also have a diagnosis of rapid-eye movement sleep 
behavior disorder (RBD) confirmed by historically 
documented polysomnography or by RBD screening 
questionnaire. 
I 03. 
Age ≥18 years to 80 years, inclusive, at the time of signing 
the informed consent (FOR JAPANESE PATIENTS ONLY: 
Age ≥20 years to 80 years, inclusive, at the time of signing 
the informed consent. Note: Japanese patients refers only 
to Japanese patients enrolled and living in Japan). 
I 04. 
Has symptoms of PD for ≥2 years. 
I 05. 
Hoehn and Yahr (H&Y) stage of ≤2 for PD at baseline; for 
patients on a stable dose of PD medication, this should be 
done in the “ON” state. 
I 06. 
If on levodopa or any other PD medication (such as a 
dopamine agonist), the medication regimen must be stable 
for at least 30 days (at least 60 days for rasagiline) prior to 
randomization. 
I 07. 
Cooperative, able to ingest oral medication, and able to 
complete all aspects of the study and capable of doing so, 
alone, according to the Investigator’s judgment. 
I 08. 
The patient is willing to abstain from consumption of 
grapefruit, grapefruit juice, and/or grapefruit containing 

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products for 72 hours prior to administration of the first dose 
of GZ/SAR402671 and for the duration of the entire 
treatment period (Part 1 and Part 2, Periods 2 and 3). 
I 09. 
Able to provide a signed written informed consent. 
 
Exclusion criteria: 
Exclusion criteria related to study methodology: 
E 01. 
Parkinsonism due to drug(s) and/or toxin(s). 
E 02. 
Patients carrying the LRRK2 G2019S mutation. 
E 03. 
Patients with Gaucher disease (GD) as defined by 
clinical signs and symptoms (ie, hepatosplenomegaly, 
cytopenia, skeletal disease) and/or marked deficiency 
of glucocerebrosidase (GCase) activity compatible 
with GD. 
E 04. 
MoCA score of <20.  
E 05. 
Patients who have past surgical history of deep brain 
stimulation. 
E 06. 
Patients who have a baseline MRI without contrast 
showing a structural abnormality that is a possible 
etiology of PD related signs and symptoms. 
E 07. 
Any medical disorders and/or clinically relevant 
findings in the physical examination, medical history, 
or laboratory assessments that, in the opinion of the 
Investigator, could interfere with study-related 
procedures (eg, heart failure, hypokalemia, etc). This 
includes condition(s) that precludes the safe 
performance of routine LP, such as prohibitive lumbar 
spinal disease, bleeding diathesis, or clinically 
significant coagulopathy or thrombocytopenia. 
E 08. 
Current participation in another investigational 
interventional study.  
E 09. 
Current treatment with anticoagulants (eg, coumadin, 
heparin) that might preclude safe completion of the 
LP. 
E 10. 
An investigational medicinal product (IMP), including 
ambroxol, within 3 months or 5 half-lives, whichever is 
longer, before study inclusion. 
E 11. 
Presence of severe depression as measured by Beck 
Depression Inventory, second edition (BDI-II) >28 
and/or a history of a major affective disorder within 
1 year of screening examination. 
E 12. 
A history of drug and/or alcohol abuse within the past 
year prior to the first screening visit. 
E 13. 
A known hypersensitivity to DAT scan (either the 
active substance of ioflupane I-123 or to any of the 
excipients). 
E 14. 
The patient is sexually active and is not willing to use 
2 forms of birth control during the study and up to 
90 days after the day of last dose. 
- 
Women of childbearing potential (WOCBP) not 

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protected by 2 highly effective methods of birth control 
and/or who are unwilling or unable to be tested for 
pregnancy for up to 45 days after the day of last dose.  
- 
Male participants must use 2 forms of birth control 
during the study and refrain from donating sperm up to 
90 days after the day of last dose. If the patient has a 
female partner of childbearing potential, the patient 
must wear a condom and female partner must use at 
least 1 highly effective method of birth control. 
E 15. 
The patient is scheduled for in-patient hospitalization 
including elective surgery during the study.  
E 16. 
The patient, in the opinion of the Investigator, is 
unable to adhere to the requirements of the study. 
This includes any patient who, in the judgment of the 
Investigator, is likely to be noncompliant during the 
study, or unable to cooperate because of a language 
problem or poor mental development. 
E 17. 
Any country-related specific regulation that would 
prevent the subject from entering the study. 
E 18. 
Any patient who is the Investigator or any 
Sub-Investigator, research assistant, pharmacist, 
study coordinator, other staff or relative thereof 
directly involved in the conduct of the study. 
E 19. 
Know hypersensitivity to GZ/SAR402671 or any 
component of the excipients. 
 
Exclusion related to active comparator and/or mandatory background 
therapies: 
E 20. 
Use of any medication specifically used for treating 
memory dysfunction, such as, but not limited to 
cholinesterase inhibitors or memantine within 30 days 
or 5 half-lives, prior to randomization, whichever is 
longer. 
E 21. 
The use of concomitant medications that prolong the 
time from ECG Q wave to the end of the T wave or 
corrected T wave corresponding to electrical systole 
(QT/QTc interval). 
Exclusion criteria related to current knowledge of GZ/SAR402671 
IMP: 
E 22. 
Liver enzymes (alanine aminotransferase [ALT] 
/aspartate aminotransferase [AST]) or total bilirubin 
>2 times the upper limit of normal (ULN) at the time of 
screening. Patients with Gilbert’s disease are 
excluded only from Part 1 participation. 
E 23. 
Renal insufficiency as defined by creatinine 
>1.5 times ULN at the screening visit. 
E 24. 
The patient has a documented diagnosis, as per local 
regulations, of any of the following infections: 
hepatitis B, hepatitis C, human immunodeficiency 
virus 1 or 2. 
E 25. 
The patient has received strong or moderate inducers 

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or inhibitors of CYP3A4 within 30 days or 5 half-lives 
of these medications, prior to randomization, 
whichever is longer.  
E 26. 
Use of the following medications within 5-elimination 
half-lives prior to the DAT neuroimaging evaluation: 
amoxapine, amphetamine, benztropine, bupropion, 
buspirone, cocaine, mazindol, methamphetamine, 
methylphenidate, norepinephrine, phentermine, 
phenylpropanolamine, selegiline, sertraline, 
citalopram, and paroxetine. 
E 27. 
The patient has, according to World Health 
Organization Grading, a cortical cataract >one-quarter 
of the lens circumference (Grade cortical cataract-2) 
or a posterior subcapsular cataract >2 mm (Grade 
posterior subcapsular cataract-2). Patients with 
nuclear cataracts will not be excluded. 
E 28. 
The patient is currently receiving potentially 
cataractogenic medications, including a chronic 
regimen (more frequently than every 2 weeks) of any 
dose or route of corticosteroids or any medication that 
may cause cataract or worsen the vision of patients 
with cataract (eg, glaucoma medications) according to 
the Prescribing Information. 
E 29. 
If female, pregnant (defined as positive beta-human 
chorionic gonadotropin blood test) or lactating or 
breastfeeding. 
E 30. 
A marked baseline prolongation of QT/QTc interval on 
screening electrocardiogram (ECG) (such as a QTc 
interval >450 msec in male subjects and >470 msec 
in female subjects).  
Total expected number of patients: 
Approximately 27 (12 Japanese and 15 non-Japanese) patients will 
be treated in Part 1 of the study. The total number of patients will 
depend on the number of dose levels tested in Part 1. Patients who 
do not complete a minimum number of scheduled doses of study 
drug in Part 1 and withdraw for reasons other than safety may be 
replaced. At the end of Part 1, if patients continue to meet eligibility 
requirements, and are willing to continue in the study, they will be 
re-randomized and enrolled in Part 2. It is expected that an additional 
216 patients (108 on active treatment and 108 on placebo), for a total 
of approximately 243 patients, will be enrolled into Part 2 of this 
study.   
Expected number of sites: 
Approximately 50 sites may be selected to participate in this study 
over the entire course of this trial.  
STUDY TREATMENT(s) 
 
Investigational medicinal product:  
 
Formulation: 
GZ/SAR402671  
 
GZ/SAR402671 is provided in capsule formulation containing 4 mg or 
15 mg of GZ/SAR402671 (active moiety).  
Route of administration: 
Oral administration. 
Dose regimen: 
Part 1: placebo or 4, 8, or 15 mg of GZ/SAR402671 once per day for 
up to 36 weeks (or 52 weeks for Japanese patients). 

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Part 2: placebo or GZ/SAR402671 once per day (dose to be 
determined in Part 1) for 52 weeks (Period 2) and GZ/SAR402671 
once per day for an additional 104 weeks (Period 3, LTFU). 
ENDPOINTS 
 
Part 1:  Dose escalation phase 
Safety: 
• 
Physical examination 
• 
Neurological examination 
• 
Clinical laboratory evaluations including hematology, 
biochemistry, urinalysis, serology 
• 
Vital signs 
• 
Assessment of AEs and concomitant medication 
• 
Ophthalmic examination  
• 
ECG 
Pharmacodynamic: 
• 
In plasma, GL-1 and lyso-GL1. Additional plasma and 
serum biomarkers may be included. 
• 
In CSF, GL-1 and lyso-GL1. Additional CSF biomarkers 
may be included. 
Pharmacokinetic: 
Plasma parameters include: 
• 
Day 1 (single dose administration): Maximum plasma 
concentration observed (Cmax), time to reach Cmax (tmax), 
and area under the plasma concentration versus time curve 
calculated using the trapezoidal method over a pre-defined 
time period (from time t= 0 to 24 hours [AUC0-24], and from 
t= 0 to 48 hours [AUC0-48]) 
• 
Week 2: Plasma concentration observed just before 
treatment administration during repeated dosing (Ctrough) 
• 
Week 4: Ctrough, Cmax, tmax, AUC0-24, and apparent total body 
clearance of a drug at steady state after oral administration 
(CLss/F; calculated using the following equation:  
CLss/F = Dose/AUCτ, where τ is the dosing interval) 
• 
Week 8: Ctrough 
Cerebrospinal fluid (CSF) parameters include: 
• 
Day -14 to Day 1: pre-dose concentration 
• 
Week 4: Concentration at any time within 2 to 4 hours after 
administration of GZ/SAR402671 
NOTE: Plasma and CSF collections for the same time points at 
Week 4 should be performed in as close succession as possible.  
Efficacy: 
• 
Change in Movement Disorder Society-Unified Parkinson’s 
Disease Rating Scale (MDS-UPDRS) PART II+III score, 
performed during the OFF state, from baseline to 4 weeks. 
• 
Change in MDS-UPDRS PART II+III score, performed 
during the OFF state, from baseline to 8 weeks. 
• 
Change in MDS-UPDRS PART I+II+III, performed during 
the OFF state, from baseline to 4 weeks. 

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• 
Change in MDS-UPDRS PART I+II+III, performed during 
the OFF state, from baseline to 8 weeks. 
 
Part 2: Treatment phase 
Primary endpoint 
• 
Change in MDS-UPDRS PART II+III score, performed 
during the OFF state, from baseline to Week 52. 
 
Secondary endpoints 
• 
Change in Parkinson's Disease-Cognitive Rating Scale 
(PD-CRS; total score) from baseline to Week 52.  
• 
Change in MDS-UPDRS PART I+II+III, performed during 
the OFF state, from baseline to Week 52. 
• 
Change in H&Y score from baseline to Week 52. 
Exploratory endpoints 
Changes from baseline to Week 26 in the following (all patients): 
• 
Biomarkers GL-1 and lyso-GL-1 levels in plasma. 
Changes from baseline to Week 52 in the following (all patients): 
• 
Change in DAT scan assessment score in predefined areas 
of interest, such as the caudate nucleus. 
• 
Time to initiation of levodopa or other PD therapy (for 
patients not on levodopa/other PD therapy at baseline) or to 
increased dose of levodopa/other PD therapy (for patients 
on levodopa/other PD therapy at baseline). 
• 
Reduction of levodopa/PD therapy (for patients on 
levodopa/other PD therapy at baseline). 
• 
GL-1, lyso-GL-1 levels in CSF and plasma. 
• 
GCase activity in CSF and dried blood spot. 
• 
Biomarkers related to neurodegeneration in plasma and/or 
in CSF, such as α-Syn, NFL, tau, phospho-tau, as well as 
beta amyloid (1-40, and 1-42). 
• 
Change in MDS-UPDRS (total score), performed during the 
OFF state. 
• 
Change in MDS-UPDRS individual subscores (Parts I, II, III, 
and IV). 
• 
PD-CRS subscores (the subcortical scale [items 1, 3, 4, 5, 
7, 8, 9]) and the cortical scale (items 2 and 6). 
• 
MoCA score. 
• 
Symbol Digit Modalities Test (SDMT) oral score.  
• 
Trail-Making Test A (TMT-A) and Trail-Making Test B 
(TMT-B) score including the change in the difference 
between TMT-B minus TMT-A score. 
• 
Clinical Global Impression (CGI) scale subscores (such as 
CGI of Improvement). 
• 
Beck Depression Inventory, second edition. 
• 
Parkinson's Disease Questionnaire - 39 (PDQ-39) score. 
• 
EuroQol five dimensions questionnaire (EQ-5D). 

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• 
Health-Related Productivity Questionnaire (HRPQ). 
• 
Falls Efficacy Scale (FES) 
Changes from baseline to Week 104, Week 156, and Week 208 in 
the following (all patients): 
• 
Change in MDS-UPDRS PART II+III score, performed 
during the OFF state. 
• 
Change in PD-CRS; total score. 
• 
Change in MDS-UPDRS PART I+II+III, performed during 
the OFF state. 
• 
Change in H&Y score. 
• 
Change in DAT scan assessment score in predefined areas 
of interest, such as the caudate nucleus. 
• 
Time to initiation of levodopa or other PD therapy (for 
patients not on levodopa/other PD therapy at baseline) or to 
increased dose of levodopa/other PD therapy (for patients 
on levodopa/other PD therapy at baseline). 
• 
Reduction of levodopa/PD therapy (for patients on 
levodopa/other PD therapy at baseline). 
• 
GL-1, lyso-GL-1 levels in plasma. 
• 
GCase activity in dried blood spot. 
• 
Biomarkers related to neurodegeneration in plasma, such 
as α-Syn, NFL, tau, phospho-tau, as well as beta amyloid 
(1-40, and 1-42). 
• 
Change in MDS-UPDRS (total score), performed during the 
OFF state. 
• 
Change in MDS-UPDRS individual subscores (Parts I, II, III, 
and IV). 
• 
PD-CRS subscores (the subcortical scale [items 1, 3, 4, 5, 
7, 8, 9]) and the cortical scale (items 2 and 6). 
• 
MoCA score. 
• 
SDMT oral score.  
• 
TMT-A and TMT-B score including the change in the 
difference between TMT-B minus TMT-A score. 
• 
Beck Depression Inventory, second edition. 
• 
PDQ-39 score. 
• 
EQ-5D. 
• 
HRPQ. 
• 
FES. 
 
The data collected during the study will be used to develop a 
Parkinson’s disease progression model in early stage PD patients 
carrying a GBA mutation. 
Pharmacokinetic assessments 
Plasma parameters include: 
• 
Day 1 (single dose administration): Cmax, tmax, AUC0-24  
• 
Week 2: Ctrough 

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• 
Week 26:  
- 
Ctrough 
- 
Concentration at any time within 2 to 4 hours after 
administration of GZ/SAR402671 on visit day.  
• 
Week 52:  
- 
Ctrough 
- 
Concentration at any time within 2 to 4 hours after 
administration of GZ/SAR402671 on visit day. 
Cerebrospinal fluid parameters include: 
• 
Day -14 to Day 1: pre-dose concentration 
• 
Week 52 (all patients):  concentration at any time within 2 to 
4 hours after administration of GZ/SAR402671 on visit 
days.   
NOTE: Plasma and CSF collections for the same time points at 
Week 52 should be performed in as close succession as 
possible.  
Exploratory GZ/SAR402671 metabolite PK profiling and/or metabolite 
exposure analysis may be performed on plasma and CSF samples 
collected during Part 1 and Part 2 of the study. 
Safety endpoints 
• 
Incidence, relationship to study drug and resolution of 
treatment-emergent adverse events (TEAEs), SAE, 
TEAE/SAE leading to study drug or study discontinuation. 
• 
Ophthalmological assessments. Visual acuity and lens 
evaluation will be performed according to the Lens Opacity 
Classification System II (LOCSII) for monitoring potential 
cataract development. 
ASSESSMENT SCHEDULE 
See Study Flowcharts (Section 1.3).  
For Part 1, the study will comprise of at least 9 visits including the 
screening visit (V1: Day -60 to Day -1); V2 (Day 1), V3 (Day 2), V4 
(Day 3), V5 (Week 2), V6 (Week 4/Day 1), V7 (Week 4/Day 2), V8 
(Week 8), and V9. Visit 8 will be repeated every 4 weeks until the 
completion of Part 1. Visit 9 is a safety follow-up completion visit. See 
note below for further instructions for premature treatment 
discontinuation.  
Using Day 1 as reference, a time frame of ± 3 days is acceptable for 
Visits 5 to 9 of Part 1 study visits. (If one visit date is 
skipped/missed/changed, the next visit should take place according 
to the original schedule). 
Note: If there is no CSF exposure, the study may be stopped. 
For Part 2, the study will comprise 16 visits (22 visits in Japanese 
patients) including the screening visit (V1: Day -60 to Day -1); V2 
(Day 1) through V9 (Week 52) for safety assessments and efficacy 
evaluations in the blinded treatment period; V10 (Week 78) 
(V9.1: Week 65 in Japanese patients) through V15 (Week 208) for 
safety assessments and efficacy evaluations in the LTFU period; and 

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V16 (Week 216) for the post-treatment observation visit.  
Note: At the end of the 52-week blinded treatment period, all patients 
will be evaluated for safety and efficacy, and for eligibility to transition 
to the LTFU period and receive GZ/SAR402671. 
Note: For patients transitioning to a long-term study with 
GZ/SAR402671, Week 208 (V15) will be the last study visit. 
Using Day 1 as reference, a time frame of ± 3 days is acceptable from 
Visit 4 to 8 of Part 2 study visits, and ± 14 days for Visit 9 and 16. (If 
one visit date is skipped/missed/changed, the next visit should take 
place according to the original schedule).  
Patients will be followed in the LTFU period for 36 months 
(156 weeks).  
Note: All patients who prematurely discontinue study medication prior 
to Week 8 (Visit 8) in Part 1, or Week 52 (Visit 9) in Period 2 or 
Week 208 (Visit 15) in Period 3 of Part 2 will be asked to continue 
study visits for safety and efficacy assessments up to and including 
the last scheduled visit. At a minimum, the patient should be followed 
up for at least 8 weeks after their last scheduled received dose. 
Patients who prematurely and permanently discontinue study 
medication should complete an end of treatment assessment visit 
(similar to Week 8/Visit 8 in Part 1 or Week 52/Visit 9 in Part 2 [for 
either Period 2 or 3]) followed by a 8-week post-treatment follow-up 
visit (similar to Visit 9 in Part 1 or Visit 16 in Part 2 [for either Period 2 
or 3]). If the following examinations including lumbar puncture, DAT 
scan, and PK analyses on plasma and CSF have been performed 
recently, then the Investigator can discuss with Sponsor the need to 
repeat these examinations. Repeat examination(s) will be done on a 
patient by patient basis. 
STATISTICAL CONSIDERATIONS 
 
Sample size determination  
Part 1: Dose escalation phase 
As Part 1 is an exploratory, dose-escalation study, the sample size is 
not based on the statistical power calculation. Each cohort (for 
non-Japanese patients only) will have a 4:1 randomization ratio, and 
the total sample size will be approximately 15 patients (including 
12 on GZ/SAR402671 and 3 on placebo).  
For Japanese patients only, each cohort will have a 
3:1 randomization ratio, and the total sample size will be 
approximately 12 Japanese patients (including 9 on GZ/SAR402671 
and 3 on placebo). This sample size in Japanese Part 1 is considered 
based upon empirical and feasibility considerations. 
The total sample size in Part 1 will be approximately 27 patients. 
Part 2: Treatment phase 
Approximately 216 PD patients carrying a GBA mutation in total will 
be randomized in a 1:1 ratio to the GZ/SAR402671 or placebo group. 
A sample size of 108 patients for the GZ/SAR402671 group and 
108 for the placebo group provides at least 80% power to detect a 
4.06 points improvement compared to the placebo mean change in 
MDS-UPDRS Parts II+III score over 52 weeks. This sample size 
calculation assumes a 2-sided alpha = 0.05, a standard deviation for 
the change from baseline to Week 52 in MDS-UPDRS Part II+III of 
10.01 points (estimated from the Parkinson's Progression Markers 
Initiative [PPMI] database), and allows for an approximate 10% early 

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terminations/unevaluable patients.  
Of note, the approximate 27 early-stage PD patients carrying a GBA 
mutation from Part 1 may be re-randomized and participate in all of 
the assessments in Part 2 of this study; however, they will not 
contribute to the primary efficacy, safety, PK and pharmacodynamics 
analyses, and will be described separately. 
Analysis populations 
Part 1: Dose escalation phase 
The Part 1 safety population is defined as all randomized patients in 
Part 1 who received at least 1 dose of study medication. All safety 
analyses in Part 1 will be performed on the Part 1 safety population. 
Patients will be summarized based on the treatment they received. 
The Part 1 Japanese safety population will be defined as all 
Japanese randomized patients in Part 1 who received at least 1 dose 
of study medication in Part 1 of the study. All safety analyses in 
Japanese Part 1 of the study will be performed on the Part 1 
Japanese safety population. 
The Part 1 pharmacodynamics and PK populations will be defined as 
all patients in Part 1 who received at least 1 dose of GZ/SAR402671 
and who have at least one pharmacodynamics or PK assessment, 
respectively. 
The Part 1 Japanese pharmacodynamics and PK populations will be 
defined as all Japanese patients in Part 1 who received at least 
1 dose of GZ/SAR402671 and who have at least one 
pharmacodynamics or PK assessment, respectively. 
Part 2: Treatment phase 
The Part 2 intent-to-treat (ITT) population is defined as all 
randomized patients in Part 2. Patients from Part 1 who are re-
randomized in Part 2 will not be included in Part 2 ITT population. 
The Part 2 ITT population is the primary analysis population for all 
efficacy endpoints. Patients will be analyzed in the treatment group to 
which they were randomized. 
The Part 2 safety population is defined as all randomized patients in 
Part 2 who received at least 1 dose of study medication in Part 2 of 
the study. Patients from Part 1 who are re-randomized in Part 2 will 
not be included in Part 2 safety population, and will be described 
separately. All safety analyses in Part 2 will be performed on the 
Part 2 safety population. Patients will be summarized based on the 
treatment they received. 
The Part 2 pharmacodynamics and PK populations will be defined as 
all patients in Part 2 who received at least 1 dose of GZ/SAR402671 
and who have at least one pharmacodynamics or PK assessment, 
respectively. Patients from Part 1 who are re-randomized in Part 2 will 
not be included in Part 2 pharmacodynamics and PK populations, 
and will be described separately. 
The Part 2 Japanese pharmacodynamics and PK populations will be 
defined as all Japanese patients in Part 2 who received at least 
1 dose of GZ/SAR402671 and who have at least one 
pharmacodynamics or PK assessment, respectively. Patients from 
Part 1 who are rerandomized in Part 2 will not be included in Part 2 
Japanese pharmacodynamics and PK populations, and will be 
described separately. 

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Analysis of efficacy (Part 2 only)  
The primary efficacy endpoint is the change from baseline to 
Week 52 in MDS-UPDRS Part II+III score. 
The primary analysis will be based on an ITT approach, including all 
data regardless of adherence to treatment and protocol. Change from 
baseline in MDS-UPDRS Part II+III score will be analyzed using a 
mixed effect model with repeated measures (MMRM). All 
postbaseline data available within Week 13 to Week 52 analysis 
windows will be used. 
Pharmacodynamics and pharmacokinetics analysis (Part 1 and 
Part 2) 
Pharmacodynamics and PK data will be described separately for 
Part 1 and Part 2 of the study, and separately for Japanese and 
non-Japanese patients. 
Pharmacodynamic parameters will be summarized and compared 
between GZ/SAR402671 and placebo administration using 
descriptive statistics at each time point, including assessment of 
observed values and percent change from baseline. p-Values for 
statistical comparisons will be provided for descriptive purpose. 
Plasma PK parameters will be summarized using descriptive statistics 
and also analyzed using noncompartmental methods. Cerebrospinal 
fluid exposure of GZ/SAR402671 will be summarized using 
descriptive statistics at each time point. 
PK parameters may be estimated for metabolites using 
noncompartmental methods and reported for individual patients and 
summarized using descriptive statistics. 
Safety (Part 1 and Part 2) 
Safety data will be described separately for Part 1, and Part 2 of the 
study, and separately for Japanese and non-Japanese patients. 
Treatment-emergent AEs will be tabulated (counts and percentages). 
Serious adverse events and discontinuations due to AEs will be 
summarized. Descriptive statistics will be generated by time point for 
selected safety parameters of interest. Data may include absolute 
and percent change from baseline values. 
DURATION OF STUDY PERIOD 
(PER PATIENT) 
Part 1 
Total duration: up to approximately 50 weeks (or 68 weeks for 
Japanese patients), in total. Patients will receive either placebo or 
GZ/SAR402671. Dosing will be for minimum 8 weeks per cohort and 
maximum of 36 weeks (or 52 weeks for Japanese patients), for 
Cohort 1. After 4 weeks of dosing, an internal blinded data review will 
occur, ensuring no safety/tolerability issues, the next cohort of 
patients will be dosed.  
Part 2 
Total duration: up to approximately 208 weeks (4 years), excluding 
Periods 1 and 4. 
There are 4 study periods: 
Period 1: up to 60 days of screening period;  
Period 2: up to 52 weeks of blinded treatment period; 
Period 3: up to 156 weeks LTFU period when all patients will be on 
active drug; and, 

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Period 4: 8-week post-treatment observation period/end of study 
visit. 
Therefore, maximum duration for a patient will be approximately 
224 weeks. 
At the end of Period 2, all patients will be evaluated for eligibility to 
transition to the LTFU period (Period 3) where they will continue to 
receive appropriate monitoring and will receive GZ/SAR402671. It is 
important to note that patients will not be informed of when the switch 
will occur, nor will the person(s) performing any of the evaluations. 
 

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1 
FLOW CHARTS 
1.1 
GRAPHICAL STUDY DESIGN FOR PART 1 
  
Screening
60 days max
safety assessment 
to follow
safety assessment 
to follow
GZ/SAR402671
4 mg, PO, qd
N = 4
Placebo
PO, qd
N = 1
enrollment pause
BASELINE:
CSF           Safety
Imaging
Efficacy 
END of 4 WEEKS:
CSF   Safety   MDS-UPDRS
R
END of every 4 WEEKS
until Part 1 completion*:
Safety    MDS-UPDRS
Screening
60 days max
safety assessment 
to follow
safety assessment 
to follow
GZ/SAR402671
8 mg, PO, qd
N = 4
Placebo
PO, qd
N = 1
R
Screening
60 days max
safety assessment 
to follow
safety assessment 
to follow
GZ/SAR402671
15 mg, PO, qd
N = 4
Placebo
PO, qd
N = 1
R
Cohort 1
Cohort 2
Cohort 3
*: daily dosing of 
placebo or GZ/SAR402671
will continue until Part 1
completion; max 36 weeks
of study medication exposure
 
Abbreviations: CSF: cerebrospinal fluid; LP: lumbar puncture; max: maximum; MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; N: number of subjects; PO: oral; qd: once daily; 
R: randomization. 
** The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1 pre-dose). Only 1 sample will be collected, during screening or 
at Day 1. 

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1.2 
GRAPHICAL STUDY DESIGN FOR PART 2 
 
 
Abbreviations: CSF: cerebrospinal fluid; LP: lumbar puncture; max: maximum; N: number of patients; PO: oral; qd: once daily; R = randomized; W = weeks. 
* The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1 pre-dose). Only 1 sample will be collected, during screening or at 
Day 1; LP at baseline will not be required to confirm eligibility of patients from Part 1 to enroll in Part 2. 
** The dose of GZ/SAR402671 will be determined in Part 1. 
R
GZ/SAR402671
PO, qd
N = 108
Screening 
60 days max 
Placebo
PO, qd
N = 108
Baseline *
52 W 
CSF (all)
Imaging
Efficacy 
CSF (all)
Imaging
Efficacy 
26 W 
Efficacy
GZ/SAR402671 **
PO, qd 
208 W 
End of Period 2
Clinic Visits every
6 months 
assessments 
216W 
End of Study 
Visit/
Period 4
End of Period 3
39 W 
Efficacy
Period 1 
Blinded Treatment Period
Long -Term Follow -Up Phase
13 W 
Efficacy
Abbreviations:R: randomization; W: weeks; max: maximum; CSF: cerebrospinal fluid; pts: patients; LP: lumbar puncture. 
• The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of 
randomization (Day 1 pre -dose). Only one sample will be collected, during screening or at Day 1.
• The dose of GZ/SAR402671 will be determined in Part 1.

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1.3 
STUDY FLOW CHART 
1.3.1 Part 1: Study schedule of assessments 
Study Period 
Screening 
D-60 to D-1 
Blinded Treatment Period  
Day (D) or Week (W) (allowed range) 
W0 
         D1                  D2              D3 
W2 
(± 3 days) 
W4 (± 3 days) 
   D1         D2 
W8 
(± 3 days) 
W12-36 (W12-52 for 
Japanese patients 
only) 
(± 3 days)a 
Part 1 Completion  
Visit (± 3 days)b 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
8.1 – 8.7 
(8.1 – 8.11, for 
Japanese patients 
only) 
9 
Site visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Demography 
X 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
GBA complete gene sequencing and LRRK2 
G2019S genotypingc 
X 
 
 
 
 
 
 
 
 
 
Medical/surgical history and PD history 
X 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
RBD history (if applicable)d 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
MRIe (without contrast) 
X 
 
 
 
 
 
 
 
 
 
Lumbar puncturee  
 
Xf 
 
 
 
X 
 
 
 
Study treatment administration 
 
 
 
 
 
 
 
 
 
 
GZ/SAR402671 or placebo  
 
X 
Drug 
holiday 
X 
qd (min 8 weeks per cohort, max 36 weeks for Cohort 1, max 52 
weeks for Japan Cohort 1) 
 
Dispense IMP 
 
X 
 
 
 
X 
 
X 
X 
 
Dispense/check patient diary 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xg 
Safety 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
X 
 
X 
X 
X 
Neurological examination 
X 
X 
 
 
X 
X 
 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
Archival blood sampleh 
 
X 
 
 
 
 
 
 
 
 
Vital signs, body temperaturei 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and biochemistry 
X 
X 
 
 
X 
X 
 
 
X 
X 

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Study Period 
Screening 
D-60 to D-1 
Blinded Treatment Period  
Day (D) or Week (W) (allowed range) 
W0 
         D1                  D2              D3 
W2 
(± 3 days) 
W4 (± 3 days) 
   D1         D2 
W8 
(± 3 days) 
W12-36 (W12-52 for 
Japanese patients 
only) 
(± 3 days)a 
Part 1 Completion  
Visit (± 3 days)b 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
8.1 – 8.7 
(8.1 – 8.11, for 
Japanese patients 
only) 
9 
Urinalysis  
X 
X 
 
 
X 
X 
 
 
X 
X 
Serum β-HCG pregnancy test (for WOCBP) 
X 
 
 
 
 
 
 
 
 
 
Urine pregnancy test (for WOCBP) 
 
X 
 
 
 
 
 
X 
X 
X 
Ophthalmology examinationj 
X 
 
 
 
 
X 
 
X 
X 
X 
12-lead ECG 
X 
Xk 
 
 
 
X 
 
 
Xk 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Biomarkers 
 
 
 
 
 
 
 
 
 
 
Biomarkers: CSFl 
 
Xf 
 
 
 
Xm 
 
 
 
 
Biomarkers: serum and plasman 
 
X 
 
 
X 
X 
 
 
 
 
GCase: dried blood spoto 
X 
 
 
 
 
 
 
 
 
DNA (optional)  
(Not applicable in Israel) 
 
 
 
 
 
 
 
 
 
 
Pharmacogenetics DNA samplep 
 
X 
 
 
 
 
 
 
 
 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
 
Plasma samples 
 
Xq 
X 
X 
X 
Xq 
X 
X 
 
 
CSF samples 
 
Xe,f 
  
 
 
Xm,r 
 
 
 
 
Assessmentss 
 
 
 
 
 
 
 
 
 
 
DAT scan 
 
X 
(Pre-dose) e,t 
 
 
 
 
 
 
 
 
MDS-UPDRS (including H&Y)  
Xu 
X 
 
 
 
X 
 
X 
X 
 
PD-CRS 
X 
X 
 
 
 
 
 
X 
 
 
MoCA 
X 
X 
 
 
 
 
 
X 
 
 
SDMT (Oral) 
 
X 
 
 
 
 
 
X 
 
 
TMT-A; TMT-B 
 
X 
 
 
 
 
 
X 
 
 
BDI-II 
Xv 
X 
 
 
X 
X 
 
X 
X 
X 
CGI 
 
X 
 
 
 
 
 
X 
 
 
PGIC 
 
 
 
 
 
 
X 
 
 
PDQ-39 
 
X 
 
 
 
 
 
X 
 
 

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Study Period 
Screening 
D-60 to D-1 
Blinded Treatment Period  
Day (D) or Week (W) (allowed range) 
W0 
         D1                  D2              D3 
W2 
(± 3 days) 
W4 (± 3 days) 
   D1         D2 
W8 
(± 3 days) 
W12-36 (W12-52 for 
Japanese patients 
only) 
(± 3 days)a 
Part 1 Completion  
Visit (± 3 days)b 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
8.1 – 8.7 
(8.1 – 8.11, for 
Japanese patients 
only) 
9 
EQ-5D 
 
X 
 
 
 
 
 
X 
 
 
HRPQ 
 
X 
 
 
 
 
 
X 
 
 
Abbreviations: α-Syn: α-synuclein; β-HCG: beta-human chorionic gonadotropin; AE: adverse event; BDI-II: Beck Depression Inventory, second edition; CGI: Clinical Global Impression; CSF: cerebrospinal fluid; 
DAT: dopamine transporters; DAT scan, ioflupane I-123 injection DaTSCAN; DBS: dried blood spot; ECG: electrocardiogram; EQ-5D: EuroQol Five Dimensions questionnaire; GBA: glucocerebrosidase gene; 
GCase: glucocerebrosidase; GL-1: glucosylceramide; H&Y: Hoehn and Yahr; HRPQ: Health-Related Productivity questionnaire; IMP: investigational medicinal product; LP: lumbar puncture; lyso-GL-1: 
glucosylsphingosine; max: maximum; MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; min: minimum; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; 
NFL: neurofilament light chain; PD: Parkinson’s disease; PD-CRS: Parkinson's Disease-Cognitive Rating Scale; PDQ-39: Parkinson's Disease Questionnaire - 39; PGIC: Patient Global Impression of Change; PK: 
pharmacokinetics; qd: once daily; RBD: rapid eye movement sleep behavior disorder; SDMT: Symbol Digit Modalities Test; TMT-A: Trail Making test A; TMT-B: Trail Making test B; WOCBP: women of childbearing 
potential. 
a This visit must be repeated for all ongoing patients every 4 weeks until all patients from Cohort 3 complete Part 1. A maximum of 36 weeks of treatment will be allowed (applicable to patients in Cohort 1), ie, up to 
7 additional visits (8.1-8.7) may be required. In Japan, a maximum of 52 weeks of treatment will be allowed (applicable to patients in Cohort 1), ie, up to 11 additional visits (8.1-8.11) may be required. 
b This is the Part 1 completion visit and it should be done 6 weeks after last IMP dose; this visit also applies to early withdrawal or treatment discontinuation, if applicable.  
c Once the results of the GBA gene sequencing (positive for a GBA mutation) and the LRRK2 genotyping (negative for the G2019S mutation) are confirmed, the remaining of the screening activities can continue.  
d Confirmed by historically documented polysomnography or by RBD screening questionnaire. 
e Once patients demonstrate eligibility based on screening criteria, MRI, LP, and DAT scan will be performed. Baseline MRI must be done at least 7 days prior to the end of the screening period (Day -8). DAT scans 
will be performed only in countries where it is approved. 
f 
The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1 pre-dose). Only one LP will be performed, during screening or at 
Day 1. If the baseline LP coincides with the baseline MRI, MRI must be done prior to LP. 
g Retrieve patient diary. 
h This sample will be collected and stored for use if any unexpected safety issue occurs to ensure that a pre-dose baseline value is available for previously nonassessed parameters (eg, serology). 
i 
In addition to body temperature, other vital signs to be captured include: respiratory rate, heart rate, systolic, and diastolic blood pressure. 
j 
Full ophthalmology examination and photography must be done during screening, at Week 36 (or Week 52 for Japanese patients), if applicable, and at the completion visit, early withdrawal or treatment 
discontinuation, if applicable. Visual acuity check, slit lamp examination and fundoscopy without pupil dilation are only required at Week 4, and at Weeks 12 and 28 (Week 36 for Japanese patients only), if 
applicable. Pupil dilation/full evaluation can be performed at any time if deemed medically necessary. When neurological and ophthalmological examinations are performed on the same day, the neurological 
examination should be performed before the ophthalmological examination. Please see Section 9.3.3.6 for more details. 
k Electrocardiograms to be performed at multiple timepoints on Day 1: pre-dose, and 2, 4, and 6 hours postdose.  If applicable, an ECG should be performed at Week 28.  
l 
Cerebrospinal fluid biomarkers, including GL-1, lyso-GL-1, α-Syn, NFL, tau, phospho-tau, as well as beta-amyloid (1-40, and 1-42). 
m Sample to be collected within 2 to 4 hours post GZ/SAR402671 administration (plasma and CSF samples in the same patient should be collected as close as possible). See detailed flowcharts in Section 1.4.1 for 
timing of assessments. 
n Plasma or serum biomarkers, including plasma GL-1, lyso-GL-1. With respect to an unscheduled visit, plasma or serum biomarker samples should only be taken if the patient has a known AE. 
o One whole blood sample will be collected and spotted on cards at the clinical site and both the sample and the card must be sent to the laboratory doing the genetic testing.  
p DNA sample will be stored to support possible future investigation of potential biomarkers for response to GZ/SAR402671. The patient must sign a separate and optional consent form for pharmacogenetics (DNA) 
analysis only. Of note, the DNA sample should be collected at the baseline, but it may be collected at any visit during the study.  
q Multiple plasma PK assessments occur on this study day. See detailed flowcharts in Section 1.4.1 for timing of assessments.  

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r 
Cerebrospinal fluid PK assessments. See detailed flowcharts in Section 1.4.1 for timing of assessments. 
s Baseline efficacy assessments should be conducted prior to GZ/SAR402671 administration on Day 1. For patients already on PD medications at the time of randomization, all efficacy assessments must be 
done in the patient’s “OFF” state (no PD medication may be taken for at least 12 hours prior to the first efficacy assessment). See also footnote u. 
t 
Baseline DAT scan may be done within 7 days prior to randomization (Day -7 to Day -1) or on the day of randomization (Day 1 pre-dose). 
u Baseline H&Y for patients on a stable dose of PD medication must be done on the “ON” state (see inclusion criterion I 05). 
v At screening, patients with BDI-II of 20-28, inclusive, should be evaluated by a mental health specialist before the Investigator can determine if the patient would be able to fully participate in the trial. Patients with a 
BDI-II of >28 (severe depression) at screening will be excluded. 
Note: When several items take place at the same time, the following order should be respected: vital signs; plasma sampling for pharmacodynamics, PK, and safety; LP, IMP administration.  
Note: Pregnancy testing after screening will be done by urine dipstick testing and must be conducted prior to imaging; pregnancy testing is required for all female patients capable of bearing children. Pregnancy tests 
may be performed more frequently in some countries due to local legislations related to WOCBP randomized in clinical trials. 
Note: For Japan only, patients should be hospitalized for Visit 2 through 4, in principle; however, if hospitalization does not occur, the Investigator should follow up each day with a phone call to check if the patients 
experience any AEs (patients living alone must be hospitalized for Visit 2 through 4). 

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Page 26 
1.3.2 Part 2: Study schedule of assessments (Periods 1 and 2) 
Study Period 
Screeninga 
Blinded Treatment Period  
Day (D) or Week (W) (allowed range) 
D-60 to  
D-1 
W0 
          D1                   D2 
W2 
(± 3 days) 
W4 
(± 3 days) 
W13u 
(± 3 days) 
W26u 
(± 3 days) 
W39u 
(± 3 days) 
W52b,u 
(± 14 
days) 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Site visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Demography 
X 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
X 
GBA complete gene sequencing and LRRK2 
G2019S genotypinga,c 
X 
 
 
 
 
 
 
 
 
Medical/surgical history and PD history 
X 
 
 
 
 
 
 
 
 
RBD history (if applicable)d 
X 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization  
 
X 
 
 
 
 
 
 
 
MRIa,e (without contrast) 
X 
 
 
 
 
 
 
 
 
Lumbar puncturea,e  
 
Xf 
 
 
 
 
 
 
X 
Study treatment administration 
 
 
 
 
GZ/SAR402671 or placebo  
 
qd 
Dispense IMP 
 
X 
 
 
X 
X 
X 
X 
Xg 
Dispense/check patient diary 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
 
X 
 
 X 
Neurological examination 
X 
X 
 
 
 
X 
X 
X 
 X 
Height 
X 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
X 
Archival blood sampleh 
 
X 
 
 
 
 
 
 
 
Vital signs, body temperaturei 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
Hematology and biochemistry 
X 
X 
 
X 
 
X 
X 
X 
 X 
Urinalysis  
X 
X 
 
X 
 
X 
X 
X 
 X 
Serum β-HCG pregnancy test (for WOCBP) 
X 
 
 
 
 
 
 
 
 

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Page 27 
Study Period 
Screeninga 
Blinded Treatment Period  
Day (D) or Week (W) (allowed range) 
D-60 to  
D-1 
W0 
          D1                   D2 
W2 
(± 3 days) 
W4 
(± 3 days) 
W13u 
(± 3 days) 
W26u 
(± 3 days) 
W39u 
(± 3 days) 
W52b,u 
(± 14 
days) 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Urine pregnancy test (for WOCBP) 
 
X 
 
 
 
X 
X 
X 
X 
Ophthalmology examj 
X 
 
 
 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
 
 
X 
 
X 
 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
Biomarkers 
 
 
 
Biomarkers: CSFk 
 
Xf 
 
 
 
 
 
 
X 
Biomarkers: serum and plasmal 
 
X 
 
X 
X 
X 
X 
X 
X 
GCase: dried blood spota,m 
X 
 
 
 
 
 
 
 
X 
DNA (optional) 
(Not applicable in Israel) 
 
 
 
 
 
 
 
 
Pharmacogenetics DNA samplen 
 
X 
 
 
 
 
 
 
X 
Pharmacokinetics 
 
 
 
Plasma samples 
 
Xo 
X 
X 
 
 
Xo 
 
Xo 
CSF samples 
 
Xf,p 
  
 
 
 
 
 
X 
Assessmentsq 
 
 
 
DAT scana,e 
 
X 
(Pre-dose)e,r  
 
 
 
 
 
 
X 
MDS-UPDRS (including H&Y)  
Xs 
X 
 
 
 
X 
X 
X 
X 
PD-CRS 
X 
X 
 
 
 
X 
X 
X 
X 
MoCA 
X 
X 
 
 
 
X 
X 
X 
 X 
SDMT (oral) 
 
X 
 
 
 
X 
X 
X 
X 
TMT-A; TMT-B 
 
X 
 
 
 
X 
X 
X 
 X 
BDI-II 
Xt 
X 
 
X 
X 
X 
X 
X 
X 
CGI 
 
X 
 
 
 
 
 
 
X 
PGIC 
 
 
 
 
 
X 
X 
X 
X 
PDQ-39 
 
X 
 
 
 
X 
X 
X 
X 
EQ-5D 
 
X 
 
 
 
X 
X 
X 
X 
FES 
 
X 
 
 
 
X 
X 
X 
X 
HRPQ 
 
X 
 
 
 
X 
X 
X 
X 

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Property of the Sanofi Group - strictly confidential 
Page 28 
Abbreviations: α-Syn: α-synuclein; β-HCG: beta-human chorionic gonadotropin; AE: adverse event; BDI-II: Beck Depression Inventory, second edition; CGI: Clinical Global Impression; CSF: cerebrospinal fluid; 
DAT: dopamine transporters; DAT scan, ioflupane I-123 injection DaTSCAN; DBS: dried blood spot; ECG: electrocardiogram; EQ-5D: EuroQol Five Dimensions questionnaire; FES: Falls Efficacy Scale; GBA: 
glucocerebrosidase gene; GCase: glucocerebrosidase; GL-1: glucosylceramide; H&Y: Hoehn and Yahr; HRPQ: Health-Related Productivity Questionnaire; IMP: investigational medicinal product; LP: lumbar puncture; 
lyso-GL 1: glucosylsphingosine; MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; NFL: neurofilament 
light chain; PD: Parkinson’s disease; PD-CRS: Parkinson's Disease-Cognitive Rating Scale; PDQ-39: Parkinson's Disease Questionnaire - 39; PGIC: Patient Global Impression of Change; PK: pharmacokinetics; qd, 
daily; RBD: rapid eye movement sleep behavior disorder; SDMT: Symbol Digit Modalities Test; TMT-A: Trail Making test A; TMT-B: Trail Making test B; WOCBP: women of childbearing potential. 
a For patients who have previously completed Part 1, the following will NOT have to be repeated: GBA mutation and LRRK2 screening, GCase: dried blood spot, MRI, LP, and DAT scan. 
b This visit will serve as the screening for patients enrolling into Period 3. 
c Genetic screening will not need to be repeated to confirm eligibility of patients from Part 1 to enroll in Part 2. Once the results of the GBA gene sequencing (positive for a GBA mutation) and the LRRK2 genotyping 
(negative for the G2019S mutation) are confirmed, the remaining of the screening activities can continue.  
d Confirmed by historically documented polysomnography or by RBD screening questionnaire.  
e Once patients demonstrate eligibility based on screening criteria, MRI, LP, and DAT scan will be performed, except for the patients who completed these baseline assessments in Part 1. Baseline MRI must be 
done at least 7 days prior to the end of the screening period (Day -8). DAT scans will be performed only in countries where it is approved. 
f 
The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1, pre-dose). Only one LP will be performed, during screening or at 
Day 1. If the baseline LP coincides with the baseline MRI, MRI must be done prior to LP. LP at baseline will not be required to confirm eligibility of patients from Part 1 to enroll in Part 2. 
g This dispensing is only for patients moving on to Period 3. 
h This sample will be collected and stored for use if any unexpected safety issue occurs to ensure that a preadministration baseline value is available for previously nonassessed parameters (eg, serology). This 
sample will not be required for patients from Part 1 to enroll in Part 2. 
i 
Multiple assessments occur on this study day. In addition to body temperature, other vital signs to be captured include: respiratory rate, heart rate, systolic, and diastolic blood pressure. Orthostatic vital signs will 
be done at screening, Weeks 4 and 52; at all other time points, vital signs will be done in the supine position.  
j 
Full ophthalmology examination and photography must be done during screening and at Week 52, early withdrawal or treatment discontinuation, as applicable. Visual acuity check, slit lamp examination and 
fundoscopy without pupil dilation are only required at Week 4, Week 13, Week 26, and Week 39. Pupil dilation/full evaluation can be performed at any time if deemed medically necessary. At Visits 1, 6, 7, 8, and 9, 
when neurological and ophthalmological examinations are performed on the same day, the neurological examination should be performed before the ophthalmological examination. 
k Cerebrospinal fluid biomarkers, including GL-1, lyso-GL-1, α-Syn, NFL, tau, phospho-tau, as well as beta-amyloid (1-40, and 1-42).  
l 
Plasma or serum biomarkers, including plasma GL-1, lyso-GL-1. With respect to an unscheduled visit, plasma or serum biomarker samples should only be taken if the patient has a known AE. 
m One whole blood sample will be collected and spotted on cards at the clinical site and both the sample and the card must be sent to the laboratory doing the genetic testing.  
n DNA sample will be stored to support possible future investigation of potential biomarkers for response to GZ/SAR402671. The patient must sign a separate and optional consent form for pharmacogenetics (DNA) 
analysis only. Of note, the first DNA sample should be collected at baseline after eligibility criteria are met, but it may be collected at any visit during the study. This sample will not be required for patients from Part 
1 to enroll in Part 2. The second DNA sample should be collected at Week 52 or at any visit after Week 52. 
o Multiple plasma PK assessments occur on this study day. See detailed flowcharts in Section 1.4.2 for timing of assessments.  
p Cerebrospinal fluid PK assessments. See detailed flowcharts in Section 1.4.2 for more detail with respect to the timing of assessments. 
q Baseline efficacy assessments should be conducted prior to GZ/SAR402671 administration on Day 1. For patients already on PD medications at the time of randomization, all efficacy assessments must be 
done in the patient’s “OFF” state (no PD medication may be taken for at least 12 hours prior to the first efficacy assessment). See also footnote s.   
r 
Baseline DAT scan may be done within 7 days prior to randomization (Day -7 to Day -1) or on the day of randomization (Day 1 pre-dose). 
s Baseline H&Y for patients on a stable dose of PD medication must be done on the “ON” state (see inclusion criterion I 05). 
t 
At screening, patients with BDI-II of 20-28, inclusive, should be evaluated by a mental health specialist before the Investigator can determine if the patient would be able to fully participate in the trial. Patients with a 
BDI-II of >28 (severe depression) at screening will be excluded.  
u Visit window extended up to 3 months, during Covid-19 outbreak (Section 10.1.2). 
Note: When several items take place at the same time, the following order should be respected: vital signs; plasma sampling for pharmacodynamics, PK, and safety; LP, IMP administration.  
Note: Pregnancy testing after screening will be by urine dipstick testing and must be conducted prior to imaging; pregnancy testing is required for all female patients capable of bearing children. Pregnancy tests may 
be performed more frequently in some countries due to local legislations related to WOCBP randomized in clinical trials. 
 

Amended Clinical Trial Protocol 06   
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GZ/SAR402671 - ACT14820  
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Property of the Sanofi Group - strictly confidential 
Page 29 
1.3.3 Part 2: Study schedule of assessments (Periods 3 and 4) 
Study Period 
Long-Term Follow-up Period (Period 3) 
8-Week 
Follow-
up Visit 
(Period 
4) 
Day (D) or 
Week (W) 
(allowed 
range) 
W65f 
(± 7 days) 
W78f 
(± 7 days) 
W91f 
(± 7 days) 
W104 (2 
years)f 
(± 7 days) 
W117f 
(± 7 days) 
W130f (± 7 
days) 
W143f 
(± 7 days) 
W156f 
(3 years) 
(± 7 days) 
W169f 
(± 7 
days) 
W182f 
(± 7 
days) 
W195f 
(± 7 
days) 
W208f 
(4 years) 
(± 7 
days)  
W216f 
(± 14 
days)a 
Visit number 
9.1 
(for 
Japanese 
patients 
only) 
10 
10.1 
(for 
Japanese 
patients 
only) 
11 
11.1 
(for 
Japanese 
patients 
only) 
12 
12.1 
(for 
Japanese 
patients 
only) 
13 
13.1 
(for 
Japanese 
patients 
only) 
14 
14.1 
(for 
Japanese 
patients 
only) 
15 
16 
Visit at clinical 
site 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study treatment 
administration 
 
 
GZ/SAR402671 
qd 
 
Dispense IMP 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Dispense/check 
patient diary 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Xb 
Xb 
Biomarkersc 
 
 
Biomarkers: 
serum and 
plasma 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Safety 
 
 
Physical 
examination 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 

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Page 30 
Study Period 
Long-Term Follow-up Period (Period 3) 
8-Week 
Follow-
up Visit 
(Period 
4) 
Day (D) or 
Week (W) 
(allowed 
range) 
W65f 
(± 7 days) 
W78f 
(± 7 days) 
W91f 
(± 7 days) 
W104 (2 
years)f 
(± 7 days) 
W117f 
(± 7 days) 
W130f (± 7 
days) 
W143f 
(± 7 days) 
W156f 
(3 years) 
(± 7 days) 
W169f 
(± 7 
days) 
W182f 
(± 7 
days) 
W195f 
(± 7 
days) 
W208f 
(4 years) 
(± 7 
days)  
W216f 
(± 14 
days)a 
Visit number 
9.1 
(for 
Japanese 
patients 
only) 
10 
10.1 
(for 
Japanese 
patients 
only) 
11 
11.1 
(for 
Japanese 
patients 
only) 
12 
12.1 
(for 
Japanese 
patients 
only) 
13 
13.1 
(for 
Japanese 
patients 
only) 
14 
14.1 
(for 
Japanese 
patients 
only) 
15 
16 
Neurological 
examination 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Vital signs, body 
temperature 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Hematology 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Biochemistry, 
urinalysis  
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Urine pregnancy 
test (for 
WOCBP) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Ophthalmology 
examinationd 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
12-lead ECG 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Adverse event 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessmentse 
 
 
DAT scan 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 

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Page 31 
Study Period 
Long-Term Follow-up Period (Period 3) 
8-Week 
Follow-
up Visit 
(Period 
4) 
Day (D) or 
Week (W) 
(allowed 
range) 
W65f 
(± 7 days) 
W78f 
(± 7 days) 
W91f 
(± 7 days) 
W104 (2 
years)f 
(± 7 days) 
W117f 
(± 7 days) 
W130f (± 7 
days) 
W143f 
(± 7 days) 
W156f 
(3 years) 
(± 7 days) 
W169f 
(± 7 
days) 
W182f 
(± 7 
days) 
W195f 
(± 7 
days) 
W208f 
(4 years) 
(± 7 
days)  
W216f 
(± 14 
days)a 
Visit number 
9.1 
(for 
Japanese 
patients 
only) 
10 
10.1 
(for 
Japanese 
patients 
only) 
11 
11.1 
(for 
Japanese 
patients 
only) 
12 
12.1 
(for 
Japanese 
patients 
only) 
13 
13.1 
(for 
Japanese 
patients 
only) 
14 
14.1 
(for 
Japanese 
patients 
only) 
15 
16 
MDS-UPDRS 
(including H&Y) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
PD-CRS 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
MoCA 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
SDMT (oral) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
TMT-A; TMT-B 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BDI-II 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
PDQ-39 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
EQ-5D 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
FES 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HRPQ 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Abbreviations: AE, adverse event; BDI-II: Beck Depression Inventory, second edition; CGI: Clinical Global Impression; DAT: dopamine transporters; DAT scan, ioflupane I-123 injection DaTSCAN; ECG: 
electrocardiogram; EQ-5D: EuroQol Five Dimensions questionnaire; FES: Falls Efficacy Scale; GL-1: glucosylceramide; H&Y: Hoehn and Yahr; HRPQ: Health-Related Productivity questionnaire; IMP, investigational 
medicinal product; lyso-GL-1: glucosylsphingosine; MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; MoCA: Montreal Cognitive Assessment; PD: Parkinson’s disease; PD-CRS: 
Parkinson's Disease-Cognitive Rating Scale; PDQ-39: Parkinson's Disease Questionnaire – 39; qd, daily; SDMT: Symbol Digit Modalities Test; TMT-A: Trail-Making Test A; TMT-B: Trail Making Test B; WOCBP: 
women of childbearing potential. 

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a This is the study completion visit, and it should be done 8 weeks after last IMP dose; this visit also applies to early withdrawal or treatment discontinuation, if applicable. This does not apply to patients who will 
transition to a long-term study with GZ/SAR402671 (last visit will be week 208). 
b Retrieve patient diary. For patients transitioning to a long-term study with GZ/SAR402671 the patient diary will be retrieved at week 208. 
c Plasma biomarkers, including plasma GL-1 and lyso-GL-1. 
d After 52 weeks, the patient is required to have a full ophthalmological examination at Weeks 104, 156, 208, and early withdrawal or treatment discontinuation, if applicable. Visual acuity check, slit lamp 
examination and fundoscopy without pupil dilation are only required at Weeks 78, 130, 182, and 216 (at the 8-week follow-up [Period 4] visit). Pupil dilation/full evaluation can be performed at any time if deemed 
medically necessary. 
e For patients already on PD medications at the time of randomization, all efficacy assessments must be done in the patient’s “OFF” state (no PD medication may be taken for at least 12 hours prior to the first 
efficacy assessment). 
f 
Visit window extended up to 3 months, during Covid-19 outbreak (Section 10.1.2). 
 
Note: Visits in Weeks 65, 91, 117, 143, 169, and 195 are for Japanese patients only. 
 

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Page 33 
1.4 
PHARMACOKINETIC SAMPLING FLOW CHARTS 
1.4.1 Part 1: Dose escalation phase 
 
Week 0/day 1 
Week 0 
/day 2 
Week 0 
/day 3 
Week 2 
(±3 days) 
Week 4/day 1 
(±3 days) 
Week 4 
/day 2 
Week 8 
(±3 days) 
Time (hour) 
Pre 
dose 
0 h 
1 ha 
2 hb 
4 hc 
8 hd 
24 he 
48 hf 
0 h 
Pre 
dose 
0 h 
Pre 
dose 
0 h 
1 ha 
2 hb 
4 hc 
8 hd 
24 he 
0 h 
Pre 
dose 
0 h 
GZ/SAR402
671 or 
placebo 
 
X 
 
 
 
 
DRUG 
HOLIDAY 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
X 
Plasma 
sample for 
PK 
P01g 
 
 
P02 
P03 
P04 
P05 
P06 
P07g 
 
P08g 
 
P09g 
 
P10 
P11 
P12 
P13 
P14e,g 
 
P15g 
 
CSF 
sample for 
PK 
C01h  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C02i 
 
 
 
 
 
Abbreviations: CSF: cerebrospinal fluid; LP: lumbar puncture; PK: pharmacokinetics. 
a Blood sample must be collected within 1 hour ± 10 minutes. 
b Blood sample must be collected within 2 hours ± 15 minutes. 
c Blood sample must be collected within 4 hours ± 30 minutes. 
d Blood sample must be collected within 8 hours ± 60 minutes. 
e Blood sample must be collected within 24 hours ± 60 minutes after the Day 1 dose. 
f 
Blood sample must be collected within 48 hours ± 120 minutes after the Day 1 dose. 
g Sample must be collected within 1 hour before oral administration of GZ/SAR402671. On these days, patients will take GZ/SAR402671 at the clinical site. 
h The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1, pre-dose). The CSF sample for PK will be done at the same time. 
i 
Sample to be collected within 2 to 4 hours post GZ/SAR402671 administration (plasma and CSF samples in the same patient should be collected as close as possible). 
 

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Page 34 
1.4.2 Part 2: Treatment phase 
 
Week 0/day 1 
Week 0/ 
day 2 
Week 2 
(±3 days) 
Week 26 (±3 days) 
Week 52 (±14 days) 
Time (hour) 
Pre-dose 
0 h 
1 ha 
2 hb 
4 hc 
8 hd 
24 he 
0 h 
Pre-dose 
0 h 
Pre-dose 
0 h 
2b - 4c h 
Pre-dose 
0 h 
2b – 4c h 
GZ/SAR402671 or 
placebo 
 
X 
 
 
 
 
 
X  
(NO DRUG 
HOLIDAY) 
 
X 
 
X 
 
 
X 
 
Plasma sample for PK 
P01f 
 
P02 
P03 
P04 
P05 
P06f 
 
P07f 
 
P08f 
 
P09g 
P10f 
 
P11g 
CSF sample for PK 
C01h 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C02g 
Abbreviations: CSF: cerebrospinal fluid; LP: lumbar puncture; PK: pharmacokinetics. 
a Blood sample must be collected within 1 hour ± 10 minutes. 
b Blood sample must be collected within 2 hours ± 15 minutes. 
c Blood sample must be collected within 4 hours ± 30 minutes. 
d Blood sample must be collected within 8 hours ± 60 minutes. 
e Blood sample must be collected within 24 hours ± 60 minutes after the Day 1 dose. 
f 
Sample must be collected within 1 hour before oral administration of GZ/SAR402671. On these days, patients will take GZ/SAR402671 at the clinical site.  
g Sample to be collected within 2 to 4 hours post GZ/SAR402671 administration (plasma and CSF samples in the same patient should be collected as close as possible).  
h The LP may be done during the screening period within 14 days prior to randomization (Day -14 to Day -1) or on the day of randomization (Day 1, pre-dose). The CSF sample for PK will be done at the same time. LP at 
baseline will not be required to confirm eligibility of patients from Part 1 to enroll in Part 2. 

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2 
TABLE OF CONTENTS 
 
AMENDED CLINICAL TRIAL PROTOCOL 06 .............................................................................................. 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................................................................... 3 
DOCUMENT HISTORY ................................................................................................................................... 3 
OVERALL RATIONALE FOR THE AMENDMENT ........................................................................................ 4 
1 
FLOW CHARTS ............................................................................................................................. 20 
1.1 
GRAPHICAL STUDY DESIGN FOR PART 1 ................................................................................ 20 
1.2 
GRAPHICAL STUDY DESIGN FOR PART 2 ................................................................................ 21 
1.3 
STUDY FLOW CHART .................................................................................................................. 22 
1.3.1 
Part 1: Study schedule of assessments ......................................................................................... 22 
1.3.2 
Part 2: Study schedule of assessments (Periods 1 and 2) ............................................................ 26 
1.3.3 
Part 2: Study schedule of assessments (Periods 3 and 4) ............................................................ 29 
1.4 
PHARMACOKINETIC SAMPLING FLOW CHARTS ..................................................................... 33 
1.4.1 
Part 1: Dose escalation phase ....................................................................................................... 33 
1.4.2 
Part 2: Treatment phase ................................................................................................................ 34 
2 
TABLE OF CONTENTS ................................................................................................................ 35 
3 
LIST OF ABBREVIATIONS .......................................................................................................... 43 
4 
INTRODUCTION AND RATIONALE ............................................................................................. 45 
4.1 
INTRODUCTION ............................................................................................................................ 45 
4.2 
RATIONALE ................................................................................................................................... 46 
4.2.1 
Study rationale ............................................................................................................................... 46 
4.2.2 
Risk assessment ............................................................................................................................ 48 
5 
STUDY OBJECTIVES ................................................................................................................... 49 
5.1 
PART 1: DOSE ESCALATION PHASE ......................................................................................... 49 
5.1.1 
Primary objective ............................................................................................................................ 49 
5.1.2 
Secondary objectives ..................................................................................................................... 49 
5.1.3 
Exploratory objectives .................................................................................................................... 49 
5.2 
PART 2: TREATMENT PHASE ..................................................................................................... 49 

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5.2.1 
Primary objective ............................................................................................................................ 49 
5.2.2 
Secondary objectives ..................................................................................................................... 49 
5.2.3 
Exploratory objectives .................................................................................................................... 50 
6 
STUDY DESIGN ............................................................................................................................ 51 
6.1 
DESCRIPTION OF THE STUDY ................................................................................................... 51 
6.2 
DURATION OF STUDY PARTICIPATION .................................................................................... 52 
6.2.1 
Duration of study participation for each patient ............................................................................. 52 
6.2.2 
Determination of end of clinical trial (all patients) .......................................................................... 53 
6.3 
INTERIM ANALYSIS ...................................................................................................................... 53 
6.4 
STUDY COMMITTEES .................................................................................................................. 53 
6.4.1 
Data monitoring committee ............................................................................................................ 53 
6.4.2 
Scientific advisory committee ......................................................................................................... 53 
6.5 
DISCUSSION OF STUDY DESIGN ............................................................................................... 54 
7 
SELECTION OF PATIENTS .......................................................................................................... 57 
7.1 
INCLUSION CRITERIA .................................................................................................................. 57 
7.2 
EXCLUSION CRITERIA ................................................................................................................ 58 
7.2.1 
Exclusion criteria related to study methodology ............................................................................ 58 
7.2.2 
Exclusion related to active comparator and/or mandatory background therapies ......................... 59 
7.2.3 
Exclusion criteria related to current knowledge of GZ/SAR402671 IMP ....................................... 59 
8 
STUDY TREATMENTS ................................................................................................................. 62 
8.1 
INVESTIGATIONAL MEDICINAL PRODUCT ............................................................................... 62 
8.2 
NONINVESTIGATIONAL MEDICINAL PRODUCT ....................................................................... 62 
8.3 
BLINDING PROCEDURES ............................................................................................................ 62 
8.3.1 
Methods of blinding ........................................................................................................................ 62 
8.3.2 
Randomization code breaking during Parts 1 and 2 ...................................................................... 63 
8.4 
METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUP .............................................. 63 
8.5 
PACKAGING AND LABELING ...................................................................................................... 64 
8.6 
STORAGE CONDITIONS AND SHELF LIFE ................................................................................ 64 
8.7 
RESPONSIBILITIES ...................................................................................................................... 64 
8.7.1 
Treatment accountability and compliance...................................................................................... 65 
8.7.2 
Return and/or destruction of treatments ........................................................................................ 66 

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8.8 
CONCOMITANT MEDICATION ..................................................................................................... 66 
8.8.1 
CYP3A4 inducers or inhibitors ....................................................................................................... 66 
8.8.1.1 
Temporary use of strong or moderate CYP3A4 inducers or inhibitors .......................................... 67 
8.8.2 
Medications with risk to cause or worsen cataract ........................................................................ 67 
8.8.3 
Medications with risk for dopamine transporters scan imaging ..................................................... 67 
8.8.4 
Medication for treating memory dysfunction .................................................................................. 68 
8.8.5 
Medications that can prolong the QT interval ................................................................................ 68 
9 
ASSESSMENT OF INVESTIGATIONAL MEDICINAL PRODUCT .............................................. 69 
9.1 
PRIMARY AND OTHER ENDPOINTS .......................................................................................... 69 
9.1.1 
Part 1: Dose escalation phase ....................................................................................................... 70 
9.1.2 
Part 2: Treatment phase ................................................................................................................ 70 
9.2 
SECONDARY ENDPOINTS .......................................................................................................... 70 
9.2.1 
Part 1: Dose escalation phase ....................................................................................................... 70 
9.2.2 
Part 2: Treatment phase ................................................................................................................ 70 
9.2.3 
Scales and questionnaires (Part 1 and Part 2) .............................................................................. 71 
9.2.3.1 
Parkinson's disease-cognitive rating scale .................................................................................... 71 
9.2.3.2 
Hoehn & Yahr scale ....................................................................................................................... 71 
9.3 
SAFETY ENDPOINTS ................................................................................................................... 72 
9.3.1 
Part 1: Dose escalation phase ....................................................................................................... 72 
9.3.2 
Part 2: Treatment phase ................................................................................................................ 72 
9.3.3 
Safety assessments (Part 1 and Part 2) ........................................................................................ 73 
9.3.3.1 
Adverse events .............................................................................................................................. 73 
9.3.3.2 
Laboratory safety variables ............................................................................................................ 73 
9.3.3.3 
Vital signs ....................................................................................................................................... 73 
9.3.3.4 
Physical examination ..................................................................................................................... 74 
9.3.3.5 
Neurological examination ............................................................................................................... 74 
9.3.3.6 
Ophthalmological examination ....................................................................................................... 75 
9.3.3.7 
Electrocardiogram (ECG) ............................................................................................................... 75 
9.4 
EXPLORATORY AND OTHER ENDPOINTS ................................................................................ 76 
9.4.1 
Pharmacodynamic and exploratory fluid biomarkers ..................................................................... 76 
9.4.2 
Pharmacokinetics ........................................................................................................................... 77 
9.4.2.1 
Sampling time ................................................................................................................................ 77 
9.4.2.2 
Pharmacokinetics handling procedure ........................................................................................... 79 
9.4.2.3 
Bioanalytical method ...................................................................................................................... 79 
9.4.2.4 
Pharmacokinetic parameters ......................................................................................................... 80 
9.4.3 
Dopamine transporters scan assessment ..................................................................................... 80 
9.4.4 
Levodopa or other Parkinson’s disease therapy ............................................................................ 81 
9.4.4.1 
Time to initiation/intensification of levodopa/PD therapy ............................................................... 81 
9.4.4.2 
Reduction of levodopa/PD therapy ................................................................................................ 81 

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9.4.5 
Scales and questionnaires ............................................................................................................. 82 
9.4.5.1 
Montreal cognitive assessment score ............................................................................................ 82 
9.4.5.2 
Oral symbol digit modalities test score .......................................................................................... 82 
9.4.5.3 
Trail making test A and B score ..................................................................................................... 83 
9.4.5.4 
Beck depression inventory, second edition ................................................................................... 83 
9.4.5.5 
Clinical global impression scale ..................................................................................................... 84 
9.4.5.6 
Patient global impression of change scale .................................................................................... 84 
9.4.5.7 
Parkinson's disease questionnaire – 39 score ............................................................................... 85 
9.4.5.8 
EuroQol five dimensions questionnaire ......................................................................................... 85 
9.4.5.9 
Falls efficacy scale ......................................................................................................................... 86 
9.4.6 
Parkinson’s disease progression model ........................................................................................ 86 
9.5 
HEALTH-RELATED PRODUCTIVITY QUESTIONNAIRE ............................................................ 86 
9.6 
PHARMACOGENETIC ASSESSMENT ......................................................................................... 87 
9.6.1 
Optional stored DNA sample (not applicable in Israel) .................................................................. 87 
9.7 
FUTURE USE OF NON-GENOMIC SAMPLES ............................................................................ 88 
10 
STUDY PROCEDURES ................................................................................................................ 90 
10.1 
VISIT SCHEDULE .......................................................................................................................... 91 
10.1.1 
Part 1: Escalated dose phase ........................................................................................................ 92 
10.1.1.1 Visit 1: Screening from Day -60 to -1 ............................................................................................. 92 
10.1.1.2 Visit 2: Randomization/baseline at Week 0/Day 1 ......................................................................... 93 
10.1.1.3 Visit 3: Week 0/Day 2 ..................................................................................................................... 95 
10.1.1.4 Visit 4: Week 0/Day 3 ..................................................................................................................... 96 
10.1.1.5 Visit 5: Week 2 (±3 days) ............................................................................................................... 96 
10.1.1.6 Visit 6: Week 4/Day 1 (±3 days) ..................................................................................................... 97 
10.1.1.7 Visit 7: Week 4/Day 2 (±3 days) ..................................................................................................... 98 
10.1.1.8 Visit 8: Week 8 (±3 days) ............................................................................................................... 98 
10.1.1.9 Visit 9: Safety follow-up completion visit (±3 days) ...................................................................... 100 
10.1.2 
Part 2: Treatment phase .............................................................................................................. 101 
10.1.2.1 Visit 1: Screening from Day -60 to -1 (Period 1) .......................................................................... 102 
10.1.2.2 Visit 2: Randomization/baseline at Week 0/Day 1 ....................................................................... 103 
10.1.2.3 Visit 3: Week 0/Day 2 ................................................................................................................... 105 
10.1.2.4 Visit 4: Week 2 (±3 days) ............................................................................................................. 106 
10.1.2.5 Visit 5: Week 4 (±3 days) ............................................................................................................. 106 
10.1.2.6 Visit 6: Week 13 (±3 days) ........................................................................................................... 107 
10.1.2.7 Visit 7: Week 26 (±3 days) ........................................................................................................... 108 
10.1.2.8 Visit 8: Week 39 (±3 days) ........................................................................................................... 109 
10.1.2.9 Visit 9: Week 52 (±14 days) ......................................................................................................... 110 
10.1.2.10 Long term follow-up period (Period 3).......................................................................................... 112 
10.1.2.11 Eight-week follow-up visit (Period 4, end-of-study visit, Visit 16: Week 216 ±14 days) .............. 114 
10.1.2.12 Contact for IMP dispensing during Covid-19 outbreak ................................................................ 114 
10.2 
DEFINITION OF SOURCE DATA ................................................................................................ 115 

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10.3 
HANDLING OF PATIENT TEMPORARY OR PERMANENT TREATMENT 
DISCONTINUATION AND OF PATIENT STUDY DISCONTINUATION ..................................... 115 
10.3.1 
Temporary treatment discontinuation with investigational medicinal products ............................ 115 
10.3.2 
Permanent treatment discontinuation with investigational medicinal product ............................. 115 
10.3.3 
List of criteria for permanent treatment discontinuation ............................................................... 115 
10.3.4 
Handling of patients after permanent treatment discontinuation ................................................. 117 
10.3.5 
Procedure and consequence for patient withdrawal from study .................................................. 117 
10.4 
OBLIGATION OF THE INVESTIGATOR REGARDING SAFETY REPORTING ........................ 118 
10.4.1 
Definitions of adverse events ....................................................................................................... 118 
10.4.1.1 Adverse event .............................................................................................................................. 118 
10.4.1.2 Serious adverse event ................................................................................................................. 118 
10.4.1.3 Adverse event of special interest ................................................................................................. 119 
10.4.2 
General guidelines for reporting adverse events ......................................................................... 120 
10.4.3 
Instructions for reporting serious adverse events ........................................................................ 120 
10.4.4 
Guidelines for reporting adverse events of special interest ......................................................... 121 
10.4.5 
Guidelines for management of specific laboratory abnormalities ................................................ 121 
10.5 
OBLIGATIONS OF THE SPONSOR ........................................................................................... 122 
10.6 
SAFETY INSTRUCTIONS ........................................................................................................... 122 
10.6.1 
Liver function tests ....................................................................................................................... 123 
10.6.2 
Acute renal failure ........................................................................................................................ 123 
10.7 
ADVERSE EVENTS MONITORING ............................................................................................ 123 
11 
STATISTICAL CONSIDERATIONS ............................................................................................ 124 
11.1 
DETERMINATION OF SAMPLE SIZE ......................................................................................... 124 
11.2 
DISPOSITION OF PATIENTS ..................................................................................................... 125 
11.3 
ANALYSIS POPULATIONS ......................................................................................................... 125 
11.3.1 
Efficacy populations ..................................................................................................................... 125 
11.3.1.1 Intent–to-treat population ............................................................................................................. 125 
11.3.1.2 Per-protocol population ................................................................................................................ 126 
11.3.2 
Safety population ......................................................................................................................... 126 
11.3.3 
Pharmacokinetics/pharmacodynamics population ....................................................................... 126 
11.4 
STATISTICAL METHODS ........................................................................................................... 127 
11.4.1 
Extent of study treatment exposure and compliance ................................................................... 127 
11.4.2 
Analyses of efficacy endpoints ..................................................................................................... 127 
11.4.2.1 Analysis of primary efficacy endpoint........................................................................................... 127 
11.4.2.2 Analyses of secondary efficacy endpoints ................................................................................... 128 
11.4.2.3 Multiplicity considerations ............................................................................................................ 129 

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11.4.3 
Analyses of safety data ................................................................................................................ 129 
11.4.3.1 Adverse events ............................................................................................................................ 130 
11.4.3.2 Laboratory data and vital signs .................................................................................................... 130 
11.4.4 
Analyses of pharmacokinetic and pharmacodynamic variables .................................................. 130 
11.5 
INTERIM ANALYSIS .................................................................................................................... 131 
11.5.1 
Interim efficacy analysis ............................................................................................................... 131 
11.5.2 
Two-step final analysis ................................................................................................................. 131 
12 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................. 132 
12.1 
ETHICAL AND REGULATORY STANDARDS ............................................................................ 132 
12.2 
INFORMED CONSENT ............................................................................................................... 132 
12.3 
HEALTH AUTHORITIES AND INSTITUTIONAL REVIEW BOARD/INDEPENDENT 
ETHICS COMMITTEE (IRB/IEC) ................................................................................................. 132 
13 
STUDY MONITORING................................................................................................................. 134 
13.1 
RESPONSIBILITIES OF THE INVESTIGATOR(S) ..................................................................... 134 
13.2 
RESPONSIBILITIES OF THE SPONSOR ................................................................................... 134 
13.3 
SOURCE DOCUMENT REQUIREMENTS .................................................................................. 135 
13.4 
USE AND COMPLETION OF ELECTRONIC CASE REPORT FORMS (ECRFS) AND 
ADDITIONAL REQUEST ............................................................................................................. 135 
13.5 
USE OF COMPUTERIZED SYSTEMS ........................................................................................ 135 
14 
ADDITIONAL REQUIREMENTS ................................................................................................. 136 
14.1 
CURRICULUM VITAE.................................................................................................................. 136 
14.2 
RECORD RETENTION IN STUDY SITES .................................................................................. 136 
14.3 
CONFIDENTIALITY ..................................................................................................................... 136 
14.4 
PROPERTY RIGHTS ................................................................................................................... 137 
14.5 
DATA PROTECTION ................................................................................................................... 137 
14.6 
INSURANCE COMPENSATION .................................................................................................. 137 
14.7 
SPONSOR AUDITS AND INSPECTIONS BY REGULATORY AGENCIES ............................... 138 
14.8 
PREMATURE DISCONTINUATION OF THE STUDY OR PREMATURE CLOSE-OUT OF 
A SITE .......................................................................................................................................... 138 
14.8.1 
By the Sponsor ............................................................................................................................. 138 
14.8.2 
By the Investigator ....................................................................................................................... 139 

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14.9 
CLINICAL TRIAL RESULTS ........................................................................................................ 139 
14.10 
PUBLICATIONS AND COMMUNICATIONS ............................................................................... 139 
15 
CLINICAL TRIAL PROTOCOL AMENDMENTS ........................................................................ 140 
16 
BIBLIOGRAPHIC REFERENCES ............................................................................................... 141 
17 
APPENDICES .............................................................................................................................. 143 
APPENDIX A 
LIST OF COMMON GBA MUTATIONS ............................................................................ 143 
APPENDIX B 
REM SLEEP BEHAVIOR DISORDER SCREENING QUESTIONNAIRE ......................... 149 
APPENDIX C 
GUIDANCE ON CONTRACEPTIVE METHODS AND COLLECTION OF 
PREGNANCY INFORMATION .................................................................................................... 150 
APPENDIX D 
DRUGS THAT CAN PROLONG THE QT INTERVAL....................................................... 154 
APPENDIX E 
LIST OF KNOWN CYP3A4 INDUCERS/INHIBITORS ...................................................... 155 
APPENDIX F 
MOVEMENT DISORDER SOCIETY-UNIFIED PARKINSON’S DISEASE RATING 
SCALE, INCLUDING HOEHN AND YAHR .................................................................................. 156 
APPENDIX G 
PARKINSON’S DISEASE-COGNITIVE RATING SCALE ................................................. 158 
APPENDIX H 
BODY FLUID BIOMARKERS ............................................................................................ 160 
APPENDIX I 
MONTREAL COGNITIVE ASSESSMENT .......................................................................... 161 
APPENDIX J 
ORAL SYMBOL DIGIT MODALITIES TEST ...................................................................... 162 
APPENDIX K 
TRAIL MAKING TEST PARTS A & B ................................................................................ 165 
APPENDIX L 
BECK DEPRESSION INVENTORY, SECOND EDITION ................................................. 170 
APPENDIX M 
CLINICAL GLOBAL IMPRESSION OF CHANGE ............................................................ 172 
APPENDIX N 
PATIENT GLOBAL IMPRESSION OF CHANGE .............................................................. 173 
APPENDIX O 
PARKINSON'S DISEASE QUESTIONNAIRE – 39 .......................................................... 174 
APPENDIX P 
EUROQOL FIVE DIMENSIONS QUESTIONNAIRE (EQ-5D) .......................................... 177 
APPENDIX Q 
FALLS EFFICACY SCALE ................................................................................................ 179 
APPENDIX R 
HEALTH-RELATED PRODUCTIVITY QUESTIONNAIRE (HRPQ) .................................. 180 
APPENDIX S 
GENERAL GUIDANCE FOR THE FOLLOW-UP OF LABORATORY 
ABNORMALITIES BY SANOFI .................................................................................................... 182 
APPENDIX T 
COUNTRY-SPECIFIC REQUIREMENTS ......................................................................... 187 
APPENDIX U 
PROTOCOL AMENDMENT HISTORY ............................................................................. 188 

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LIST OF TABLES 
Table 1 - Number of samples for pharmacodynamics assessment .............................................................. 77 
Table 2 - Number of samples for pharmacokinetics assessment ................................................................. 78 
Table 3 - Summary of plasma and cerebrospinal fluid samples collected for GZ/SAR402671 concentrations
 ....................................................................................................................................................................... 79 
Table 4 - Summary of handling procedures for stored DNA samples ........................................................... 88 
Table 5 - Summary of adverse event reporting instructions ........................................................................ 122 
 

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3 
LIST OF ABBREVIATIONS 
 
AE: 
adverse event 
AESI: 
adverse event of special interest 
ALP: 
alkaline phosphatase 
ALT: 
alanine aminotransferase 
AST: 
aspartate aminotransferase 
AUCt: 
area under the plasma concentration versus time curve calculated using the 
trapezoidal method over a predefined time period 
BDI-II: 
Beck Depression Inventory, second edition 
CBC: 
complete blood count 
CGI: 
Clinical Global Impression 
CLss/F: 
apparent total body clearance of a drug at steady state after oral administration 
Cmax: 
maximum plasma concentration observed 
CNS: 
central nervous system 
CSF: 
cerebrospinal fluid 
CTCAE: 
Common Terminology Criteria for Adverse Events 
Ctrough: 
plasma concentration observed just before treatment administration during 
repeated dosing 
DAT: 
dopamine transporter 
DAT scan: 
ioflupane I-123 injection DaTSCAN 
DMC: 
Data Monitoring Committee  
DME: 
drug metabolizing enzyme 
ECG: 
electrocardiogram  
eCRF: 
electronic case report form 
EQ-5D: 
EuroQol Five Dimensions Questionnaire 
FDA: 
Food and Drug Administration 
FES: 
Falls Efficacy Scale 
GBA: 
β-glucocerebrosidase gene 
GBA-PD: 
Parkinson's disease patient carrying a GBA mutation 
GCase: 
glucocerebrosidase 
GCP: 
Good Clinical Practice  
GCS: 
glucosylceramide synthase 
GD: 
Gaucher disease 
GD1: 
GD type 1 
GGT: 
gamma-glutamyl transferase 
GL-1: 
glucosylceramide 
H&Y: 
Hoehn and Yahr 
HRPQ: 
Health-Related Productivity Questionnaire 
IB: 
Investigator's brochure 
ICH: 
International Council for Harmonisation 
IEC: 
Independent ethics committee 
IMP: 
investigational medicinal product 
INR: 
international normalized ratio  
IRB: 
Institutional review board 

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ITT: 
intent-to-treat 
IVRS: 
Interactive Voice Response System 
IWRS: 
Interactive Web Response System 
LOCSII: 
Lens Opacity Classification System II 
LP: 
lumbar puncture 
LTFU: 
long-term follow-up 
lyso-GL-1: 
glucosylsphingosine 
MCID: 
minimal clinically important difference  
MDS-UPDRS: 
Movement Disorder Society-Unified Parkinson's Disease Rating Scale 
MMRM: 
mixed effect model with repeated measures 
MoCA: 
Montreal Cognitive Assessment 
MRI: 
magnetic resonance imaging 
NCI: 
National Cancer Institute 
NFL: 
neurofilament light chain 
PCSA: 
potentially clinically significant abnormality  
PD: 
Parkinson's disease 
PD-CRS: 
Parkinson's Disease-Cognitive Rating Scale 
PDQ-39: 
Parkinson's Disease Questionnaire – 39 
PGIC: 
Patient Global Impression of Change 
PI: 
Principal Investigator 
PK: 
pharmacokinetics 
PP: 
per-protocol 
PPMI: 
Parkinson's Progression Markers Initiative  
PR interval: 
the time from the onset of the P wave to the start of the QRS complex 
PT: 
prothrombin time  
PTT: 
partial thromboplastin time 
qd: 
once daily 
QRS interval: 
time from ECG Q wave to the end of the s wave corresponding to ventricular 
depolarization 
QT/QTc interval: time from ECG Q wave to the end of the T wave or corrected T wave 
corresponding to electrical systole 
RBD: 
rapid eye movement sleep behavior disorder 
SAC: 
Scientific Advisory Committee 
SAE: 
serious adverse event 
SAP: 
statistical analysis plan  
SDMT: 
Symbol Digit Modalities Test 
SRT: 
substrate reduction therapy 
ST deviation: 
ECG ST-segment deviation 
SUSAR: 
Suspected Unexpected Serious Adverse Reaction 
TEAE: 
treatment-emergent adverse event 
tmax: 
time to reach Cmax 
TMT: 
Trail-Making Test 
ULN: 
upper limit of normal 
WOCBP: 
women of childbearing potential 
α-Syn: 
α-synuclein 
β-HCG: 
beta-human chorionic gonadotropin 

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4 
INTRODUCTION AND RATIONALE 
4.1 
INTRODUCTION 
Gaucher disease (GD) is the most common lysosomal storage disorder and results from the 
deficiency of the lysosomal enzyme glucocerebrosidase (GCase) that resides in lysosomes. 
Gaucher disease is caused by bi-allelic mutations in the human β-glucocerebrosidase gene (GBA) 
and follows an autosomal recessive mode of inheritance. GCase deficiency leads to the 
accumulation of its major substrate, glucosylceramide (GL-1), within the lysosomes of a variety 
of cell types, including macrophages and neurons (1), which in some patients can lead to rapid 
neurodegeneration with death by late infancy. In addition, glucosylsphingosine (lyso-GL-1), the 
deacylated form of GL-1, also accumulates as a minor substrate.  
The human GBA gene is located on chromosome 1q21 in a gene rich area. The GBA gene 
comprises 11 exons and 10 introns, spanning 7.6 kb of sequence. A nonprocessed pseudogene 
which shares 96% exonic sequence homology is located 16 kb downstream of the functional 
GBA gene (2). The presence of this highly homologous pseudogene along with another 6 genes at 
the locus increases the occurrence of chromosomal rearrangements and misalignments in this 
region. These processes provide an explanation for the high number of complex recombinant 
alleles that have been detected in GD (3). 
Parkinson's disease (PD) is a progressive neurodegenerative condition, which is characterized 
primarily by the 4 cardinal motor symptoms: resting tremor, bradykinesia, rigidity, and postural 
instability. Nonmotor features include cognitive impairment, hallucinations, autonomic 
dysfunction, and sleep disorders.  
Parkinsonism is one of the neurological symptoms described in GD, and affected individuals 
exhibit classical symptoms, including tremor, rigidity, and bradykinesia. An increased frequency 
of typical Parkinsonism was noted among otherwise healthy relatives of Gaucher patients who 
were obligate or confirmed carriers of GBA mutations (4). Further analysis of these Gaucher 
relatives revealed a possible association between heterozygous changes in GBA and 
parkinsonism, leading to subsequent mutational screening in patient cohorts with sporadic PD.  
In 2009, a large international multicenter study with 16 participating centers compared 5,691 PD 
patients of different ethnic origin with 4,898 control individuals without PD. All patients were 
screened for at least the 2 most common GBA mutations (N370S and L444P), which were found 
in 15% of Ashkenazi Jewish PD patients and in 3% of PD patients of other ethnic origin. This 
study confirmed that heterozygous mutations in the GBA gene represent the most common 
genetic factor for PD so far. Carrier frequencies for GBA mutations differed between 10% and 
31% in the Ashkenazi Jewish PD population, and 2.9% and 12% in PD cohorts of 
non-Ashkenazi-Jewish origin, such as North American (with European background), Taiwanese, 
and Italian. The lowest carrier frequency was reported to be 2.3% in Norwegian PD patients as 
compared to 1.7% in controls (5). Overall, approximately 7-10% of PD patients carry a GBA 
mutation (GBA-PD) that predisposes them to an earlier onset of PD symptoms with faster 

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cognitive and motor decline compared to sporadic PD (6), (7), (8), making them numerically the 
most important risk factor for the disease identified to date. Cognitive impairment in GBA-PD is 
characterized by impaired verbal fluency, visuospatial processing, executive planning, sustained 
attention, naming, and memory that declines rapidly over time. 
Glucocerebrosidase is present, along with α-synuclein (α-Syn), in an average of 75% of the Lewy 
bodies in the brains of GBA-PD patients (9). One hypothesis is that GL-1, a substrate of GCase, 
may promote stabilization of α-Syn into oligomers similar to those found in Lewy bodies, and 
mutations in GBA correspondingly are associated with α-Syn accumulation; at the same time, 
α-Syn impairs GCase function within lysosomes, both in PD cells and in normal cells, promoting 
further accumulation of GL-1 (10). Furthermore, the accumulation of GCase lipid substrates (ie, 
GL-1) has been reported in cultured neurons and brain tissues from PD patients carrying GBA 
mutations (11).  
4.2 
RATIONALE 
4.2.1 Study rationale 
GZ/SAR402671 is a novel glucosylceramide synthase (GCS) inhibitor that decreases the synthesis 
of GL-1. In Phase 1 healthy volunteer studies, once daily (qd) oral administration of 
GZ/SAR402671 at free base doses ranging from 3.72 mg to 14.9 mg was shown to be safe and 
reduce plasma levels of GL-1 within 2 weeks in a dose-dependent manner. In these studies, 
GZ/SAR402671 was absorbed with a median time to reach maximum plasma concentration 
observed (tmax) of 2.00 to 3.00 hours and eliminated with a pooled geometric mean terminal 
elimination half-life (t1/2z) of 31.3 hours on Day 14. 
In vitro studies demonstrate that GZ/SAR402671 is a potent and selective inhibitor of murine and 
human GCS in biochemical and cell-based assays. In vivo pharmacology studies utilized plasma 
GL-1 lowering as a pharmacodynamic marker of GCS inhibition. In vivo activity was established 
in rodents and dogs with reductions in plasma (rodent and dog) and tissue (rodents only) GL-1 
following oral administration of GZ/SAR402671. In both species, the effects of GZ/SAR402671 
on plasma GL-1 were dose-dependent and correlated with plasma exposure of the compound. In 
rodents, GZ/SAR402671 has been shown to cross the blood brain barrier and reduce the synthesis 
of the major isoform of GL-1 in the central nervous system (CNS; ie, C18 GL-1). Exposure in 
CNS has also been confirmed in dogs where the cerebrospinal fluid (CSF) concentrations of 
GZ/SAR402671 following repeat oral dosing were approximately 2-fold greater than the unbound 
plasma concentration of drug.  
To date, no large-scale studies have specifically addressed the relative benefits and risks of 
different treatments for GBA-associated PD. Thus, there is a medical need to address motor, 
cognitive, and/or neuropsychiatric manifestations in GBA-PD patients. Patients included in this 
study will be early-stage PD patients who are heterozygous carriers of a GBA mutation, aged 
18 to 80 years. 
A substrate reduction therapy (SRT) treatment approach for GD type 1 (GD1) was first 
demonstrated by miglustat (Zavesca®), which is a weak and nonspecific GCS inhibitor. Due to its 

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limited efficacy and tolerability profile, Zavesca was approved only for adult GD1 patients who 
are not candidates for enzyme replacement therapy, the standard of care. More recently, the 
therapeutic effect of SRT for the treatment of systemic disease in adults with GD1 was established 
clinically with eliglustat (Cerdelga®, genzyme, a Sanofi company), in both treatment naïve and 
previously treated patients (12), (13). Cerdelga is a specific and potent GCS inhibitor that is 
structurally unrelated to Zavesca or GZ/SAR402671. By reducing substrate influx, eliglustat 
significantly improved disease manifestations in untreated GD1 patients with existing visceral and 
hematologic involvement. In GD1 patients stabilized on enzyme replacement therapy, oral 
eliglustat as monotherapy maintained hematological and organ volume stability (13). Cerdelga 
was approved by the Food and Drug Administration (FDA) in August 2014 and by the European 
Medicines Agency in January 2015. In contrast to GZ/SAR402671, eliglustat has no or only 
limited ability to cross the blood brain barrier with negligible exposure in brain, thus, it is not 
expected to impact neurological manifestations of GD or other neuropathic disease, such as PD.   
Given the positive impact on visceral disease with Cerdelga, it is anticipated that GCS inhibitors 
with appropriate CNS exposure and activity could address neuronopathic forms of GD, ie, GD3, 
as well as GBA-PD. Preclinical investigations in mouse models of GBA-PD found viral vector 
mediated replacement of normal GBA genes in the CNS resulted in pharmacological reduction of 
GCase lipid substrates, decreased α-Syn pathology, and improved behavioral outcomes in 
2 models of synucleinopathies (14). Treatment of Gaucher-related synucleinopathy mice 
(GbaD409V/D409V) with the potent and selective GCS inhibitor Genz-667161 prevented CNS 
lyso-GL-1 accumulation. Notably, this treatment slowed the accumulation of hippocampal 
aggregates of α-Syn, ubiquitin and tau, and improved the associated memory deficits. In another 
set of studies, treatment of α-Syn overexpressing mice PrP-A53T-SNCA (harboring wild type 
alleles of GBA) with the GCS inhibitor also reduced membrane-associated α-Syn in the CNS and 
ameliorated cognitive deficits. Collectively, the data indicate that inhibition of GCS can modulate 
processing of α-Syn and reduce the progression of GBA-PD. GCS inhibition represents a new 
potentially disease-modifying treatment approach for GBA-associated PD (14).  
This is a two-part, multicenter, multiple-country, placebo-controlled, randomized, double-blind 
study which will be divided into 2 consecutive major periods: 1) a placebo-controlled, 
randomized, double-blinded dose escalation study (using 3 different doses), utilizing a sequential 
cohort design, to be followed by 2) a randomized, double-blind, placebo-controlled, 2-arm study 
of the efficacy and safety of GZ/SAR402671 in early-stage PD patients carrying a GBA mutation. 
Part 1 will be only conducted in selected sites (approximately 20 sites [including 4 Japanese 
sites]); Part 2 will be conducted at multiple sites (approximately 50). Part 2 will start only after 
satisfactory Part 1 data is reviewed and considered satisfactory. The 3 doses being evaluated in 
Part 1 will be 4 mg, 8 mg, and 15 mg; all will be oral daily dosing. The maximum dose (15 mg) 
was selected based on data from a completed Phase 1 14-day repeated oral dose study 
(TDR12768) in which it provided proof of significant biological activity in humans (plasma GL-1 
was reduced approximately 80%) and was safe and well tolerated. GZ/SAR402671 exposure in 
human CSF has not yet been investigated and will be done in Part 1 of this trial.  
Of note, the highest administered dose in Study TDR12768 was a 20 mg capsule, which 
corresponds to a 15 mg base/active dose of GZ/SAR402671. A daily dose of greater than 15 mg 
has not been tested in humans. Therefore, in the absence of biomarkers and/or pharmacodynamic 

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data to guide human active dose estimation, evaluation of the maximum dose, as supported by the 
Phase 1 trial results, will first permit determination of efficacy. 
Sanofi has considered it is scientifically appropriate to include Japanese patients in Part 1 of the 
multi-national study so that the safety and tolerability of GZ/SAR402671 in Japanese GBA-PD 
patients can be assessed, by stepwise approach, prior to enrollment of these patients into the main 
part of the study (Part 2). Understanding the safety and tolerability of GZ/SAR402671 in Japanese 
GBA-PD patients rather than in Japanese healthy subjects is important before enrolling Japanese 
GBA-PD patients into Part 2. 
Comparison of pharmacokinetics (PK) and pharmacodynamics using plasma GL-1 as the 
biomarker between Japanese and non-Japanese patients can be conducted in the global clinical 
study as part of the dose escalation part of the study (Part 1), enabling PK and pharmacodynamics 
characterization in the Japanese target population and early participation of Japanese GBA-PD 
patients in a therapeutic, potentially disease modifying study. 
4.2.2 Risk assessment 
GZ/SAR402671 has not been studied in patients with GBA-PD. In the completed Phase 1 clinical 
trials in healthy volunteers, oral administration of GZ/SAR402671 was safe and generally well 
tolerated.  
Based on toxicology data, the target tissues identified in rats were the lens, germinal epithelium of 
the testes, gastrointestinal tract, and the liver. Further analysis of data indicates that there seems to 
be no safety concern in humans involving the gastrointestinal tract and the liver. 
In a juvenile toxicology study in rats given GZ/SAR402671, unilateral/bilateral degeneration of 
germinal epithelium in the testes of males and lenticular (eye lenses) degeneration in both sexes 
were observed. Lens swelling was also reported in adult female rats given a high dose of 
20 mg/kg but no lens findings were observed in dog studies. Adult rodent and dog study data 
indicate no anticipated impact on adult male GBA-PD patient fertility. Additional information is 
provided in the GZ/SAR402671 Investigator’s Brochure (IB).  
As a result of rodent lens findings, GBA-PD patients with cataracts (excluding those with nuclear 
cataracts) are excluded from ACT14820. Furthermore, patients currently receiving potentially 
cataractogenic medications as listed in Section 7.2 are excluded. The effect of GZ/SAR402671 on 
the lens will be closely monitored throughout the clinical trial through periodic ophthalmology 
examinations as detailed in Section 9.3.3.6. Additionally, there is a theoretical risk of CNS effects 
given the compound’s access through the blood-brain barrier to the CNS. However, preclinical 
studies in rats did not suggest the occurrence of untoward effects on the CNS at the no observed 
adverse effect level of 45 mg/kg/day (approximately 10-fold the above expected clinical 
exposure). 

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5 
STUDY OBJECTIVES 
5.1 
PART 1: DOSE ESCALATION PHASE 
5.1.1 Primary objective 
To determine the safety and tolerability of 4, 8, and 15 mg of GZ/SAR402671, as compared to 
placebo, when administered orally daily for 4 weeks in early-stage PD patients carrying a GBA 
mutation or other prespecified sequence variants (from now on both mutation types are referred to 
as ‘GBA mutation’). This will allow selection of the dose for the second part of this study (this 
does not apply to Japanese patients). 
5.1.2 Secondary objectives 
To assess the PK profile of daily oral dosing of GZ/SAR402671 in plasma when administered at 
doses of 4, 8, or 15 mg over a 4-week period in early-stage PD patients carrying a GBA mutation. 
To assess the exposure of GZ/SAR402671 in CSF when administered at doses of 4, 8, or 15 mg 
over a 4-week period in early-stage PD patients carrying a GBA mutation. 
5.1.3 Exploratory objectives 
To assess the pharmacodynamic response of daily oral dosing of GZ/SAR402671 in plasma and 
CSF when administered at doses of 4, 8, or 15 mg over a 4-week period, as measured by GL-1 in 
early-stage PD patients carrying a GBA mutation. 
To explore the effect of GZ/SAR402671 on scores from selected scales and questionnaires which 
will be used in this study over an 8-week period in early-stage PD patients carrying a GBA 
mutation. 
5.2 
PART 2: TREATMENT PHASE 
5.2.1 Primary objective 
To determine the efficacy of GZ/SAR402671 in patients with early-stage PD carrying a GBA 
mutation when administered orally daily at the dose selected in Part 1, over a 52-week period, as 
compared to placebo. 
5.2.2 Secondary objectives 
To demonstrate the overall safety and tolerability of GZ/SAR402671 administered orally daily for 
52 weeks in early-stage PD patients carrying a GBA mutation as compared to placebo. 

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To assess the pharmacodynamic response to daily oral dosing of GZ/SAR402671 in plasma and 
CSF as measured by GL-1 in early-stage PD patients carrying a GBA mutation over a 52-week 
period. 
5.2.3 Exploratory objectives 
To explore the effect of GZ/SAR402671 on scores from selected scales and questionnaires which 
will be used in this study. Of note, for patients receiving levodopa or other PD medication, 
assessment of scales and questionnaires will be performed during the OFF state (ie, no PD 
medication may be taken for at least 12 hours prior to the efficacy assessments) except for the 
Hoehn & Yahr (H&Y) scale which will be completed in "ON" state only at baseline visit (see 
inclusion criteria I 05) 
To assess the effect of GZ/SAR402671 on neurologic functional status via functional 
neuroimaging over a 52-week period. 
To assess the PK profile of GZ/SAR402671 in plasma and CSF of early stage PD patients 
carrying a GBA mutation. 
To evaluate the pharmacodynamic response to GZ/SAR402671 in plasma and CSF as measured 
by lyso-GL-1 in early-stage PD patients carrying a GBA mutation. 
To explore the effect of GZ/SAR402671 on CSF biomarkers related to PD or neurodegeneration, 
including total α-Syn, neurofilament light chain (NFL), tau, phospho-tau, as well as beta-amyloid 
(1-40, and 1-42). 
To develop a Parkinson’s disease progression model in early stage PD patients carrying a GBA 
mutation. 
To assess the long-term safety and efficacy of GZ/SAR402671 over a 156-week period. 
 

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6 
STUDY DESIGN 
6.1 
DESCRIPTION OF THE STUDY 
This is a two-part, multicenter, multiple-country, randomized, double-blinded, placebo-controlled 
study in early-stage PD patients carrying a GBA mutation. The study will be divided into 
2 consecutive parts. Part 1 will be a randomized, double-blinded, placebo-controlled dose 
escalation study, utilizing a sequential cohort design. Part 1 will allow selection of the dose of 
GZ/SAR402671 for Part 2, a randomized, double-blind, placebo-controlled, 2-arm study of the 
efficacy and safety of GZ/SAR402671. Part 1 will be conducted only in selected sites 
(approximately 20 sites [including 4 Japanese sites]); Part 2 will be conducted at multiple sites 
(approximately 50). Part 2 will start after the appropriate dose for Part 2 is selected in Part 1. 
In Part 1, during the screening/baseline period, from Day -60 to Day -1, patients will provide 
informed consent and undergo screening assessments to determine trial eligibility and undergo 
baseline measurements. If all eligibility criteria are met, patients will enter the trial. Part 1 will 
determine the safety and tolerability of GZ/SAR402671 at 4, 8, and 15 mg in early-stage PD 
patients carrying a GBA mutation by using a dose escalation scheme (4 weeks to assess safety and 
tolerability of dose and a minimum of an additional 4 weeks to further assess safety and 
tolerability and any potential changes in other exploratory endpoints in each dose cohort). There 
will be 3 sequential cohorts that will be placebo-controlled: 
• Cohort 1: 4 patients on GZ/SAR402671 4 mg and 1 patient on placebo. 
• Cohort 2: 4 patients on GZ/SAR402671 8 mg and 1 patient on placebo. 
• Cohort 3: 4 patients on GZ/SAR402671 15 mg and 1 patient on placebo. 
No additional dose escalation of GZ/SAR402671 will occur above the highest proposed dose of 
15 mg. All patients must complete the first 4-week course of therapy with subsequent data review 
by an internal review committee whose purpose is to review data (such as safety, tolerability, 
and/or clinical endpoints), demonstrating safety/tolerability before dose escalation to the next 
higher level can occur. Patients will continue to be dosed daily and will be followed every 
4 weeks until the completion of Part 1, allowing for additional safety and other exploratory 
endpoints to be collected. Each cohort will have a 4:1 randomization ratio, and the total sample 
size will be approximately 15 patients (including 12 on GZ/SAR402671 and 3 on placebo). In 
Japan, each cohort will have a 3:1 ratio, and the total sample size will be approximately 
12 Japanese patients (including 9 on GZ/SAR402671 and 3 on placebo). Therefore, the total 
sample size in Part 1 will be approximately 27 patients. 
If a serious adverse event (SAE) or ≥Grade 3 adverse event (AE, National Cancer Institute [NCI], 
Common Terminology Criteria for Adverse Events [CTCAE] Version 4.03) that is considered by 
the Investigator to be related to GZ/SAR402671 and not to underlying disease or concomitant 
medication is observed, the case will be communicated to the internal review committee and a 
decision should be reached regarding escalation to the next dose with GZ/SAR402671. If 
2 patients receiving GZ/SAR402671 within the same cohort develop the same SAE or AE 
(≥Grade 3), dosing within the cohort will be stopped. After stopping, this committee will review 

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the data and provide recommendations on how to proceed. In addition, SAE/adverse events of 
special interest (AESIs) will be communicated to the Data Monitoring Committee (DMC). 
At the end of 4 weeks of treatment during the dose escalation part, patients in each cohort will 
have a lumbar puncture (LP); CSF exposure of GZ/SAR402671 will be measured at 2 time points 
in Part 1: at pretreatment and Week 4. If there is no CSF exposure at the highest dose level, the 
study will be stopped. 
In Part 2, the GZ/SAR402671 dose will be the highest dose determined to be safe and well 
tolerated in Part 1. Moreover, CSF exposure must be known. If there is no CSF exposure of 
GZ/SAR402671, then that dose will not be used in Part 2.   
If patients from Part 1 continue to meet eligibility requirements, and are willing to continue in the 
study, they may enroll in Part 2, but re-randomization will be required; furthermore, they will 
have to sign another informed consent form. All screening assessments will need to be repeated, 
except for the genetic screening, magnetic resonance imaging (MRI), LP, and ioflupane I-123 
injection DaTSCAN (DAT scan), to confirm eligibility of patients from Part 1 to enroll in Part 2. 
In Part 2, eligible patients will be stratified based on use of levodopa/PD medication (yes/no), 
cognitive function (Montreal Cognitive Assessment [MoCA]) score <26 [yes/no]) and severe 
GBA mutation (yes/no). Patients will be randomized in a 1:1 ratio to receive GZ/SAR402671 or 
placebo for 52 weeks. 
Part 2 will include 4 main periods: the up to 60-day screening period (Period 1), the 52-week 
blinded treatment period (Period 2), the 156-week duration long-term follow-up (LTFU) period 
(Period 3), and the 8-week post-treatment observation period (Period 4).  
All patients who continue to meet inclusion criteria I 06, I 07, I 08, and I 09 and none of the 
exclusion criteria (exclusion criteria E 02, E 03, E 05, and E 06 will not need to be rechecked) at 
Week 52 will be eligible to receive GZ/SAR402671 treatment during the LTFU period (Period 3).  
6.2 
DURATION OF STUDY PARTICIPATION 
6.2.1 Duration of study participation for each patient 
The maximum study duration per patient will be approximately 224 weeks (4.3 years, patients 
from Part 2 only) to 272 weeks (5.5 years, patients from Part 1 enrolling in Part 2), or to 
288 weeks for Japanese patients (5.9 years, Japanese patients from Part 1 enrolling in Part 2). 
Part 1: Dose escalation phase 
The maximum study duration per patient will be approximately 50 weeks (or 66 weeks for 
Japanese patients), inclusive of the screening period. Three sequential cohorts are planned. 
Patients will receive either placebo or GZ/SAR402671 (4 mg, 8 mg, or 15 mg) for a minimum 
8 weeks per cohort (and maximum of 36 weeks [or 52 weeks for Japanese patients], for Cohort 1). 

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Safety/tolerability data will be analyzed at the end of 4 weeks of treatment at each cohort before 
proceeding to the next cohort.  
Part 2: Treatment phase 
The total study treatment duration (Periods 2 and 3) is approximately 208 weeks (4 years). 
The study comprises 4 main periods:  
• Period 1: the up to 60-day screening period. 
• Period 2: the 52-week double-blinded, randomized treatment period. 
• Period 3: the 156-week LTFU period during which eligible patients will all receive 
GZ/SAR402671.  
• Period 4: the 8-week post-treatment observation period with end of study visit.  
Therefore, maximum duration for a patient will be approximately 224 weeks. 
6.2.2 Determination of end of clinical trial (all patients) 
The end of the study is defined as being the “last patient last visit” planned with the protocol, 
including the follow-up visit (Visit 9 in Part 1 and Visit 16 in Part 2 or Visit 15 for patients who 
will transition to a long-term study with GZ/SAR402671). The Sponsor reserves the right to 
discontinue the study at any time. 
6.3 
INTERIM ANALYSIS 
No interim analysis is planned for this study. 
6.4 
STUDY COMMITTEES 
6.4.1 Data monitoring committee 
A DMC, operating independently from the Sponsor and Clinical Investigators, will be responsible 
for overseeing the safety of patients and the risk/benefit ratio throughout the study. This 
committee is composed of externally based individuals with expertise in the disease under study, 
biostatistics, and/or clinical research. The primary responsibilities of the DMC are to ensure the 
patients welfare as well as to evaluate and review the safety and other applicable data throughout 
the course of the study and make appropriate recommendations to the Sponsor regarding the 
conduct of the clinical trial. The specific responsibilities of the DMC will be described in the 
DMC Charter. 
6.4.2 Scientific advisory committee 
The Scientific Advisory Committee (SAC) is composed of field experts and Sponsor-based 
scientists with clinical and methodological expertise. This Committee, led by a Chairperson, 
selected by the Sponsor, will provide advice to the Sponsor regarding scientific issues and 
operational conduct of the study. The SAC will also review any amendments, and provide input 

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regarding interpretation of study results. The members will remain blinded until completion of the 
study. 
Among its responsibilities, the SAC will receive blinded study status reports from the Sponsor, 
and will review the recommendations from the DMC throughout the study. 
Moreover, the SAC will also be responsible for the primary publication(s) emanating from the 
study. The Principal Investigator (PI) of the study will be selected by the Sponsor and will be the 
first author for the primary publication(s). Principal Investigators at the 3 first sites enrolling the 
most patients will also be included as authors for the primary publication, in addition to the other 
SAC members. 
Detailed activities and responsibilities of the SAC are provided in the SAC charter. 
6.5 
DISCUSSION OF STUDY DESIGN 
Current treatment options for PD patients, with or without GBA mutations, are limited due to side 
effects. Despite the many therapeutic agents available for the treatment of PD, patients can still 
experience intolerable disability due to disease progression. Thus, there is a high unmet medical 
need for better treatment alternatives in PD. Participation in this placebo-controlled study, with a 
novel mechanism of action, would present a unique opportunity for the patients. Patients will be 
allowed to start on PD therapy (only an immediate release levodopa formulation is allowed) or to 
continue to take their medication as usual (if already taking PD medication at study start).   
Of note, PD prescription medications permitted (see Section 8.8) in this trial include: 
• Dopamine replacement therapies (eg; levodopa/carbidopa). 
• Dopamine agonists (eg; pramipexole, ropinirole, bromocriptine). 
• Monoamine oxidase B inhibitors (eg; rasagiline). 
• Catechol-O-methyltransferase inhibitors (eg; entacapone, tolcapone). 
• Anticholinergics (eg; artane, cogentin). 
The following points were taken into consideration in the design of the study: 
• Screening: Sequencing of the GBA gene and genotyping for a LRRK2 (G2019S) 
mutation to ensure patient eligibility will be conducted from a collected whole blood 
sample even if historical results are available. 
• Randomization (Day 1, pre-dose): To reduce the risk of imbalance between treatment 
groups with respect to cognitive function and PD medication. In Part 2, randomization will 
be stratified based on use of levodopa/PD medication (yes/no), cognitive function (MoCA 
score <26 [yes/no]) and severe GBA mutation (yes/no). 
• Long-term follow-up (Part 2): Upon completion of the 52-week treatment period, 
eligible patients will be followed in an LTFU period for 36 months. Patients in the placebo 
arm will be switched to GZ/SAR402671 treatment after completing the Week 52 study 
visit. During the LTFU period, study drug assignment will remain blinded and patients 
will continue to be assessed by a blinded rater, thus collecting important information and 

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data. This will allow not only the long-term safety to be assessed but can also support 
long-term efficacy of GZ/SAR402671. Importantly, patients who received placebo in 
Period 2 will have the opportunity to receive GZ/SAR402671 treatment. Analysis of 
efficacy and safety between those patients who were on GZ/SAR402671 treatment from 
the start of randomization and patients who began GZ/SAR402671 treatment 1 year later 
will potentially offer insightful information on delayed start of treatment in this patient 
population.  
• Primary and secondary efficacy endpoints: The primary efficacy endpoint of the study 
is the change from baseline to Week 52 in the Movement Disorder Society-Unified 
Parkinson's Disease Rating Scale (MDS-UPDRS), PART II+III. The MDS-UPDRS was 
designed to be more comprehensive than the original UPDRS, with new items devoted to 
several nonmotor elements of PD, including cognitive function. Based on a published 
critique of the UPDRS, the 5-point range for each item was retained, and clinical anchors 
of normal (0), slight (1), mild (2), moderate (3), and severe (4) were added to provide a 
consistency across items. Importantly, the MDS-UPDRS places greater emphasis on 
distinguishing relatively mild impairments and disabilities, drawing distinctions between 
slight and mild, whereas former distinctions between severe and marked are now collapsed 
into the severe rating. The incorporation of ‘slight’ and ‘moderate’ ratings in the scale 
should result in an even more sensitive measure of disease progression in early stages. The 
subscales are now titled: (Part I) nonmotor experiences of daily living (13 items), (Part II) 
motor experiences of daily living (13 items), (Part III) motor examination (18 items), and 
(Part IV) motor complications (6 items).  
An important addition to the MDS-UPDRS is a set of detailed instructions. These are officially 
part of the scale, so that international colleagues can perform ratings in a systematic manner 
within and across centers. The instructions are intended to standardize the method of application 
of the scale so that the MDS-UPDRS data are collected uniformly. The MDS-UPDRS tool 
includes clear definitions of ‘ON’ times, when dopaminergic medications are working properly, 
and ‘OFF’ times, when the dopaminergic therapies ‘wear off’, and patients experience decreased 
mobility, to ensure uniformity of rater assessments of ON/OFF status (Note: PD medication 
cannot be taken for at least 12 hours prior to the visits including efficacy assessment). The scale 
has been translated in many different languages, and, importantly, scale reliability, construct 
validity, and precision have been assessed. It performs extremely well in comparison with the 
original version with high internal consistency for the entire scale as well as high internal 
consistency on each part. In addition, even though restructured, each part of the MDS-UPDRS 
correlates highly with the corresponding part of the original scale. 
In summary, the MDS-UPDRS is a reliable and sensitive measure of disease progression, 
particularly decline in motor function, in early stages of PD. Given the target population for this 
study is early-stage GBA-PD patients, the change in the motor parts of the MDS-UPDRS 
(PART II+III) is the most appropriate scale to use as a primary endpoint in this clinical trial. 
GBA-PD patients also experience more rapid cognitive decline as compared with PD patients 
without GBA mutations. Cognition changes in GBA-PD patients will be captured via assessment 
of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), a scale that was designed to cover 

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the full spectrum of cognitive deficits associated with PD. This secondary endpoint will allow 
important data to be gathered in this patient population.  
Given that GBA-PD patients experience nonmotor symptoms, another important secondary 
endpoint will be the MDS-UPDRS, PARTS I+II+III. Lastly, functional scales are important for 
assessment in clinical trials, allowing to support clinical meaningfulness of endpoints. The H&Y 
score has been shown to have moderate correlations with Parts I and IV, and high correlations 
with Parts II and III of the MDS-UPDRS. 
• Pharmacodynamic and exploratory biomarkers: GBA-mutations and reduced GCase 
activity can lead to elevations in plasma and CSF concentrations of substrates including 
GL-1 and lyso-GL-1. GZ/SAR402671 has shown to reduce plasma concentrations even in 
normal healthy volunteers in the repeated-dose Phase 1 study (Study TDR12768). Plasma 
and CSF samples will be stored and will be used to assess changes in GL-1 and lyso-GL-1 
to support the clinical endpoints. Glucocerebrosidase activity will be explored. In addition, 
biomarkers associated with PD and/or neurodegeneration may also be assessed in blood 
and/or CSF, such as total α-Syn, NFL, tau, phospho-tau, as well as beta-amyloid (1-40, 
and 1-42).  
• Imaging: PD, including GBA-PD, has been associated with changes in dopamine 
transport density in the basal ganglia regions in the brain, as measured by ioflupane-I-123 
injection DATSCAN™ (from now on referred to as DAT scan). Changes in DAT scans in 
predefined areas of interest, such as the caudate nucleus, from baseline to Week 52 and 
from baseline to Week 104, Week 156, and week 208 will be assessed as an exploratory 
endpoint. Please note that DAT scans will be performed only in countries where it is 
approved. 

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7 
SELECTION OF PATIENTS 
7.1 
INCLUSION CRITERIA 
I 01. Male or female subjects with a diagnosis of PD (with at least two of the following signs: 
resting tremor, postural instability, akinesia/hypokinesia, and muscle rigidity) and who are 
heterozygous carriers of a GBA mutation. Please see Section 17 (Appendix A) for the list 
of most common mutations. Note: If the patient has a GBA mutation that is not on the list, 
a consult will always be required to determine the eligibility of the patient.  
OR 
I 02. Patients carrying known sequence variants associated with GBA-PD (Section 17 
[Appendix A]), in addition to having a diagnosis of PD (with at least 2 of the following 
signs: resting tremor, postural instability, akinesia/hypokinesia or muscle rigidity), must 
also have a diagnosis of rapid eye movement sleep behavior disorder (RBD) (15) 
confirmed by historically documented polysomnography or by RBD screening 
questionnaire (see Section 17 [Appendix B]). 
I 03. Age ≥18 years to 80 years, inclusive, at the time of signing the informed consent (FOR 
JAPANESE PATIENTS ONLY: Age ≥20 years to 80 years, inclusive, at the time of 
signing the informed consent. Note: Japanese patients refers only to Japanese patients 
enrolled and living in Japan [Appendix T]). 
I 04. Has symptoms of PD for ≥2 years.  
I 05. Hoehn and Yahr stage of ≤2 for PD at baseline; for patients on a stable dose of PD 
medication, this should be done in the “ON” state. 
I 06. If on levodopa or any other PD medication (such as a dopamine agonist), the medication 
regimen must be stable for at least 30 days (at least 60 days for rasagiline) prior to 
randomization.   
I 07. Cooperative, able to ingest oral medication, and able to complete all aspects of the study 
and capable of doing so, alone, according to the Investigator’s judgment. 
I 08. The patient is willing to abstain from consumption of grapefruit, grapefruit juice, and/or 
grapefruit containing products for 72 hours prior to administration of the first dose of 
GZ/SAR402671 and for the duration of the entire treatment period (Part 1 and Part 2, 
Periods 2 and 3). 
I 09. Able to provide a signed written informed consent. 

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7.2 
EXCLUSION CRITERIA 
Patients who have met all the inclusion criteria listed in Section 7.1 will be screened for the 
following exclusion criteria which are sorted and numbered in the following subsections.  
7.2.1 Exclusion criteria related to study methodology 
E 01. Parkinsonism due to drug(s) and/or toxin(s). 
E 02. Patients carrying the LRRK2 G2019S mutation.  
E 03. Patients with GD as defined by clinical signs and symptoms (ie, hepatosplenomegaly, 
cytopenia, skeletal disease) and/or marked deficiency of GCase activity compatible with 
GD. 
E 04. MoCA score of <20. 
E 05. Patients who have past surgical history of deep brain stimulation. 
E 06. Patients who have a baseline MRI without contrast showing a structural abnormality that is 
a possible etiology of PD related signs and symptoms.  
E 07. Any medical disorders and/or clinically relevant findings in the physical examination, 
medical history, or laboratory assessments that, in the opinion of the Investigator, could 
interfere with study-related procedures (eg, heart failure, hypokalemia, etc). This includes 
condition(s) that precludes the safe performance of routine LP, such as prohibitive lumbar 
spinal disease, bleeding diathesis, or clinically significant coagulopathy or 
thrombocytopenia. 
E 08. Current participation in another investigational interventional study.  
E 09. Current treatment with anticoagulants (eg, coumadin, heparin) that might preclude safe 
completion of the LP. 
E 10. An investigational medicinal product (IMP), including ambroxol, within 3 months or 
5 half-lives, whichever is longer, before study inclusion. 
E 11. Presence of severe depression as measured by Beck Depression Inventory, second edition 
(BDI-II) >28 and/or a history of a major affective disorder within 1 year of screening 
examination. 
E 12. A history of drug and/or alcohol abuse within the past year prior to the first screening visit. 
E 13. A known hypersensitivity to DAT scan (either the active substance of ioflupane I-123 or to 
any of the excipients). 

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E 14. The patient is sexually active and is not willing to use 2 forms of birth control during the 
study and up to 90 days after the day of last dose (see contraceptive guidance in Section 17 
[Appendix C]). 
- 
Women of childbearing potential (WOCBP) not protected by 2 highly effective 
methods of birth control and/or who are unwilling or unable to be tested for pregnancy 
for up to 45 days after the day of last dose.  
- 
Male participants must use 2 forms of birth control during the study and refrain from 
donating sperm up to 90 days after the day of last dose. If the patient has a female 
partner of childbearing potential, the patient must wear a condom and female partner 
must use at least 1 highly effective methods of birth control. 
E 15. The patient is scheduled for in-patient hospitalization including elective surgery during the 
study.  
E 16. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of 
the study. This includes any patient who, in the judgment of the Investigator, is likely to be 
noncompliant during the study, or unable to cooperate because of a language problem or 
poor mental development. 
E 17. Any country-related specific regulation that would prevent the subject from entering the 
study. 
E 18. Any patient who is the Investigator or any Sub-Investigator, research assistant, pharmacist, 
study coordinator, other staff or relative thereof directly involved in the conduct of the 
study. 
E 19. Know hypersensitivity to GZ/SAR402671 or any component of the excipients. 
7.2.2 Exclusion related to active comparator and/or mandatory background therapies 
E 20. Use of any medication specifically used for treating memory dysfunction, such as, but not 
limited to cholinesterase inhibitors or memantine within 30 days or 5 half-lives of these 
medications prior to randomization, whichever is longer. 
E 21. The use of concomitant medications that prolong the time from ECG Q wave to the end of 
the T wave or corrected T wave corresponding to electrical systole (QT/QTc interval) (see 
Section 17 [Appendix D] for a list of commonly used medications). 
7.2.3 Exclusion criteria related to current knowledge of GZ/SAR402671 IMP  
E 22. Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total 
bilirubin >2 times the upper limit of normal (ULN) at the time of screening. Patients with 
Gilbert’s disease are excluded only from Part 1 participation. 
E 23. Renal insufficiency as defined by creatinine >1.5 times ULN at the screening visit. 

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E 24. The patient has a documented diagnosis, as per local regulations, of any of the following 
infections: hepatitis B, hepatitis C, human immunodeficiency virus 1 or 2. 
E 25. The patient has received strong or moderate inducers or inhibitors of CYP3A4 (see 
Section 17 [Appendix E]) within 30 days or 5 half-lives of these medications, prior to 
randomization, whichever is longer. 
E 26. Use of the following medications within 5-elimination half-lives prior to the DAT 
neuroimaging evaluation: amoxapine, amphetamine, benztropine, bupropion, buspirone, 
cocaine, mazindol, methamphetamine, methylphenidate, norepinephrine, phentermine, 
phenylpropanolamine, selegiline, sertraline, citalopram, and paroxetine. 
E 27. The patient has, according to World Health Organization Grading, a cortical cataract 
> one-quarter of the lens circumference (Grade cortical cataract-2) or a posterior 
subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2). Patients with nuclear 
cataracts will not be excluded. 
E 28. The patient is currently receiving potentially cataractogenic medications, including a 
chronic regimen (more frequently than every 2 weeks) of any dose or route of 
corticosteroids or any medication that may cause cataract or worsen the vision of patients 
with cataract (eg, glaucoma medications) according to the Prescribing Information. 
E 29. If female, pregnant (defined as positive beta-human chorionic gonadotropin [β-HCG] 
blood test) or lactating or breast-feeding. 
E 30. A marked baseline prolongation of QT/QTc interval on screening electrocardiogram 
(ECG) (such as a QTc interval >450 msec in male subjects and >470 msec in female 
subjects). 
If the patient is a screen failure, all data obtained at screening including laboratory results of 
screening tests must be available in the patient’s medical records. For screening failures, the 
following data obtained during screening will be transferred to the electronic case report form 
(eCRF) and entered into the database: informed consent date, visit date, patient’s demographic 
data, inclusion and exclusion criteria, AE data (if available) and reason for failure. 
A patient cannot be randomized more than once in the study, with the exception of those patients 
who have participated in and completed Part 1 of the trial and continue to meet eligibility criteria 
for Part 2. Patients who meet exclusion criteria in both Part 1 and Part 2 during the screening 
period may be rescreened once; a different patient identification will be issued. Rescreening is not 
permitted if the patient fails to meet inclusion criteria or if the patient carries the LRRK2 G2019S 
mutation (see exclusion criterion E 02) or has GD (see exclusion criterion E 03). There is no 
requirement for a waiting period between the screen-failure date and the rescreening date. The 
Interactive Voice Response System/Interactive Web Response System (IVRS/IWRS) report will 
flag rescreened patients. Patients that are rescreened must sign a new consent form and all Visit 1 
procedures, except the genetic screening, MRI, LP, and DAT scan, must be repeated. 

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Note: Rescreening is possible in this study in cases where the original screening failure was due to 
reasons expected to change at rescreening and based upon the Investigator’s clinical judgment. 
The patient may be rescreened once within 6 months from the time of the original screening 
failure to check whether or not they then meet all of the inclusion and none of the exclusion 
criteria. All screening assessments will need to be repeated, except the genetic screening, MRI, 
LP, and DAT scan, to confirm eligibility of the patient for the study. 
Patients who do not adhere to treatment (at least 80% compliance rate) in Part 1 and withdraw for 
reasons other than safety may be replaced. 

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8 
STUDY TREATMENTS 
8.1 
INVESTIGATIONAL MEDICINAL PRODUCT 
GZ/SAR402671 or matching placebo will be provided for oral administration as brownish red, 
opaque, hard gelatin capsules. Each drug capsule will provide a dose of either 4 mg or 15 mg of 
GZ/SAR402671 (active moiety). Each placebo capsule will provide a dose of 0 mg. 
GZ/SAR402671 can be administered without restriction to food, except for the consumption of 
grapefruit, grapefruit juice, and/or grapefruit containing products within 72 hours of starting 
GZ/SAR402671 administration. Patients should be instructed to ingest the capsules at 
approximately the same time of the day throughout the entire study. 
In Part 1, the dose of GZ/SAR402671 will be 4, 8, or 15 mg or placebo once per day for up to 
36 weeks (or 52 weeks for Japanese patients). Safety/tolerability and, eventually, CSF exposure, 
from Part 1 will determine the recommended dose for Part 2. 
In Part 2, the dose of GZ/SAR402671 determined in Part 1 or placebo will be administered once 
per day for 52 weeks (Period 2); in Period 3 (LTFU), patients will receive GZ/SAR402671 once 
per day for an additional 156 weeks. 
GZ/SAR402671 hard capsules will be packaged in blister packs. 
8.2 
NONINVESTIGATIONAL MEDICINAL PRODUCT 
Not applicable.  
8.3 
BLINDING PROCEDURES 
8.3.1 Methods of blinding 
GZ/SAR402671 and matching placebo for GZ/SAR402671 will be indistinguishable from one 
another and be provided in identically matched packaging which includes labeling to protect the 
blind. 
In accordance with the double-blind design, study patients, Investigators and study site personnel 
will remain blinded to study treatment and will not have access to the randomization list 
(treatment codes) except under circumstances described in Section 8.3.2. All samples for PK and 
biomarkers evaluation will be assessed blindly (treatment arm and timing) and results will not be 
communicated to the study personnel. The Investigators and the Sponsor will also be blinded to 
PK and biomarkers data. A Sanofi Clinical Supplies representative will remain unblinded 
throughout the study with respect to the study medication kits in order to provide the appropriate 
study drug to patients; however, sites and study teams must be blinded to PK and biomarker data 
throughout the study.  

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The blinded results at the end of 4 weeks of treatment for each patient in each dose cohort will be 
provided to an internal review committee. 
The DMC will receive blinded by treatment group or unblinded (if necessary) confidential reports 
from an independent statistician for review, which have to be handled strictly confidentially. None 
of these reports can be delivered to unauthorized persons. 
8.3.2 Randomization code breaking during Parts 1 and 2 
Blinding should only be broken for serious, unexpected, and related AEs, and only for the patient 
in question, or when required by local regulatory authorities. The Investigator must notify Sanofi 
genzyme before breaking the code for any patient as soon as possible. 
The code may be broken only in the case of a serious, unexpected related AE. If possible, contact 
should be initiated with the Monitoring Team before breaking the code.   
In case of an emergency, the IVRS can be contacted by the Investigator or Sub-Investigator to 
reveal the IMP assignment of a particular patient. In case of a Suspected Unexpected Serious 
Adverse Reaction (SUSAR), the Global Pharmacovigilance department of the Sponsor will 
contact IVRS to reveal IMP assignment for regulatory reporting requirements for the particular 
case. The IVRS unblinding procedures should be followed as outlined in the IVRS manual. 
If the blind is broken by the Investigator he/she will document the date, time of day and reason for 
code breaking. The patient must discontinue study medication, but should be encouraged to 
continue in the study, completing all assessments at the scheduled timepoints. If in Part 2, the 
patient will not be allowed to enter the LTFU (Period 3) of the study. At a minimum, the patient 
may withdraw from the clinical trial and complete an end of treatment assessment visit (similar to 
Visit 8 in Part 1 or Visit 9 in Part 2) followed by a post-treatment follow-up visit (similar to 
Visit 9 in Part 1 or Visit 16 in Part 2). If this is done, then the patient should be followed up for at 
least 8 weeks after their last scheduled received dose or until resolution of the related SAE.  
Patient withdrawal will only occur when the code break call is made at the site level and/or at the 
study level. This means that if the Emergency Unblinding transaction is performed by the 
Investigator (ie, at the site level), then the patient will be withdrawn from treatment. However, if 
the Emergency Unblinding transaction is performed by the Sponsor (ie, at the study level), then 
the patient will not be withdrawn from treatment. 
8.4 
METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUP 
A randomized treatment kit number list will be generated centrally by the Sponsor. The IMP 
(GZ/SAR402671 or placebo) will be packaged in accordance with this list. 
The Sanofi Clinical Supplies team will provide the randomized treatment kit number list and the 
Study Biostatistician will provide the randomization scheme to the centralized treatment 
allocation system. This centralized treatment allocation system will generate the patient 
randomization list according to which it will allocate the treatments to the patients.  

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The randomization and the treatment allocation will be performed centrally by an IVRS which 
will be available 24 hours a day, 7 days a week. In Part 1, randomization will not be stratified. In 
Part 2, randomization will be stratified based on use of levodopa/PD medication (yes/no), 
cognitive function (MoCA score <26 [yes/ no]), and severe GBA mutation (yes/no). 
In order to maintain blinding, the Investigator or designee will contact the IVRS to obtain a 
patient number once the patient signs the informed consent form. 
The patient number allocated by the IVRS is a specific 12-digit number consisting of: 3-digit 
country code (Independent System Operator), 4-digit site number, 5-digit sequential number at 
site with leading zeros (ie, 840-0001-00001, 840-0001-00002). 
Once eligibility is confirmed, the pharmacist (or designee) will contact the IVRS at the time of 
patient randomization in order to obtain the randomization treatment kit assignment for the 
patient, and at subsequent patient scheduled visits to obtain the correct treatment kit assignment 
for the patient. 
Patients will be allocated by the IVRS to either GZ/SAR402671 or placebo. 
All kits must be retained for accountability. 
8.5 
PACKAGING AND LABELING 
Packaging is in accordance with the administration schedule. The content of the labeling is in 
accordance with the local regulatory specifications and requirements. 
8.6 
STORAGE CONDITIONS AND SHELF LIFE 
Investigators or other authorized persons (eg, pharmacists) are responsible for storing the IMP 
provided by the Sponsor in a secure and safe place in accordance with local regulations, labeling 
specifications, policies, and procedures. 
Control of IMP storage conditions, especially control of temperature and information on in-use 
stability and instructions for handling the Sanofi compound should be managed according to the 
rules provided by the Sponsor. 
Batch and expiry date management will be assisted with IVRS. 
8.7 
RESPONSIBILITIES 
The Investigator, the site pharmacist, or other personnel allowed to store and dispense the IMP 
will be responsible for ensuring that the IMP used in the clinical trial is securely maintained as 
specified by the Sponsor and in accordance with applicable regulatory requirements. 

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All IMP will be dispensed in accordance with the Investigator's prescription and it is the 
Investigator's responsibility to ensure that an accurate record of IMP issued and returned is 
maintained. 
Any quality issue noticed with the receipt or use of an IMP (deficiency in condition, appearance, 
pertaining documentation, labeling, expiration date, etc) should be promptly notified to the 
Sponsor. Some deficiencies may be recorded through a complaint procedure. 
A potential defect in the quality of IMP may be patient to initiation of a recall procedure by the 
Sponsor. In this case, the Investigator will be responsible for promptly addressing any request 
made by the Sponsor, in order to recall the IMP and eliminate potential hazards. 
Under no circumstances will the Investigator supply IMP to a third party (except for direct-
to-patient shipment, for which a courier company has been designated by the Sponsor), allow the 
IMP to be used other than as directed by this clinical trial protocol, or dispose of IMP in any other 
manner. 
8.7.1 Treatment accountability and compliance 
The Investigator or designee will keep an accurate record of all IMP that is received, dispensed, 
and returned on a per patient basis using an IMP accountability log. 
Measures taken to ensure and document treatment compliance and IMP accountability include: 
• Accurate recording of treatment kit number as required on appropriate eCRF page for 
accounting purposes. 
• All medication treatment kits (whether empty or unused) are returned by the patient at 
each visit. 
• The Investigator or designee tracks treatment accountability/compliance, either by diary, 
or by counting the number of used treatment kits and fills in the appropriate page of the 
patient treatment log. 
• The monitor in charge of the study then checks the data entered on the IMP administration 
page by comparing them with the IMP that has been retrieved and the patient treatment log 
form. 
A patient diary will be issued to the patient at the screening visit with instructions to record any 
safety issue. For eligible patients, the same diary will be used to record missing doses after 
randomization. A brief explanation should be provided if a dose is missed. The patient should 
bring their diary and any remaining capsules to each clinic visit.  
The site staff will review the patient diary during each clinic visit and record excursions from 
treatment into the eCRF. The patient diary will be retrieved when the patient finishes their 
participation in the study. 

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8.7.2 Return and/or destruction of treatments 
Reconciliation of all used, partially used or unused treatments must be performed at the site by the 
Investigator and the monitoring team using treatment log forms. The treatment log form will be 
countersigned by the Investigator and the monitoring team. 
Authorization for destruction will be given by the Sponsor once the reconciliation has been 
completed. This destruction can be performed at the site depending on local regulations and 
site-specific capabilities; alternatively, study drug may be returned to the Sponsor or designee for 
destruction. 
8.8 
CONCOMITANT MEDICATION 
A concomitant medication is any treatment received by the patient during the study aside from the 
IMP. Concomitant medications should be kept to a minimum during the study. Furthermore, 
changes in concomitant medications should be kept to a minimum and only occur if considered to 
be absolutely necessary in the medical judgment of the Investigator. However, if these are 
considered necessary for the patient's welfare and are unlikely to interfere with the IMP, they may 
be given as rescue medication at the discretion of the Investigator and must be recorded in the 
eCRF. 
Concomitant medications, including over-the-counter, dietary supplements (eg, herbal remedies) 
or prescriptions, are permitted during the study period, except for ambroxol use which is 
forbidden throughout the study and the medications listed in the following sections (see 
Section 8.8.1, Section 8.8.1.1, Section 8.8.2, and Section 8.8.3). Any treatment not permitted at 
study entry will be forbidden throughout the study. 
Patients will be allowed to continue with their PD medication as usual, if on stable PD therapy at 
study start. However, it may be considered necessary in the medical judgment of the Investigator 
to initiate or intensify PD medications. In such occurrence, this could apply only to an immediate 
release levodopa formulation.  
The definition of stable PD therapy according to the longstanding gold standard worldwide is: 
• At least 30 days on levodopa or other PD therapy, including dopamine agonists. 
• At least 60 days on rasagiline. 
All concomitant medications reported at the time of the screening visit and for the duration of the 
patient’s participation should be recorded. 
8.8.1 CYP3A4 inducers or inhibitors 
GZ/SAR402671 should not be administered concomitantly with any strong or moderate inducers 
or inhibitors of CYP3A4 per FDA classification.  
If a patient is inadvertently administered a strong or moderate CYP3A4 inducer or inhibitor, the 
Investigator should contact the Sponsor as soon as possible. The physician should switch the 
patient to an alternative medication that is not a strong or moderate CYP3A4 inducer or inhibitor. 

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Grapefruit, grapefruit juice, and/or grapefruit products are not permitted 72 hours prior to the first 
dose of GZ/SAR402671 and for the duration of the entire treatment period (Periods 2 and 3). 
8.8.1.1 Temporary use of strong or moderate CYP3A4 inducers or inhibitors 
GZ/SAR402671 dose interruptions will not be permitted during the first 4 weeks of Part 1 or 
Part 2, Period 2. 
In Part 2, GZ/SAR402671 dose interruptions will be permitted for those patients who require 
temporary use (≤2 weeks) of strong or moderate inhibitors or inducers of CYP3A4 (see Section 17 
[Appendix E]) for the treatment of acute illness. Such medications must not be used on more than 
a total of 2 occasions (ie, up to 2 weeks per occasion for a maximum of 4 weeks of 
GZ/SAR402671 interruptions) during the treatment Period 2 (Part 2).  
In Part 2, patients must complete a minimum of 7 consecutive daily GZ/SAR402671 oral 
administrations prior to Weeks 26 and 52 assessments, except in the case of Covid-19 infection 
(see Section 10.1.2). 
8.8.2 Medications with risk to cause or worsen cataract 
Given nonclinical lens findings (see IB), a chronic regimen (ie, more frequent than once every 
2 weeks) of the following medications is forbidden during the clinical trial: 
• Corticosteroids: 
- 
May be used on a restricted basis in patients who require temporary use (≤1 week) for 
the treatment of any acute condition for which no appropriate substitute is found. Such 
medications must not be used on more than a total of 4 occasions (ie, up to 1 week per 
occasion) during the treatment periods (Period 2 and 3). 
- 
A special provision is made to allow enrollment of GBA-PD patients who require 
inhaled corticosteroids for the management of a stable medical condition (eg, allergies, 
asthma, etc), in which corticosteroid withdrawal would be detrimental. In this case, the 
Investigator would administer the lowest efficacious dose. The potential benefits 
expected by the administration of GZ/SAR402671 outweigh the potential drawbacks 
that can be observed by the initiation/worsening of cataracts. 
• Psoralens used in dermatology with ultraviolet light therapy. 
• Typical antipsychotics. 
The Investigator should consider substituting medications listed in the previous paragraphs for 
noncataractogenic treatments, as appropriate. 
In addition, glaucoma medications are excluded from the current trial since they can worsen the 
vision of patients with cataracts.   
8.8.3 Medications with risk for dopamine transporters scan imaging 
Medications that might interfere with dopamine transporter (DAT) single-photon emission 
computed tomography imaging and are restricted within 5 elimination half-lives prior to a DAT 

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scan injection include: amoxapine, amphetamine, benztropine, bupropion, buspirone, cocaine, 
mazindol, methamphetamine, methylphenidate, norepinephrine, phentermine, 
phenylpropanolamine, selegiline, sertraline, citalopram, and paroxetine.  
8.8.4 Medication for treating memory dysfunction  
Any medications specifically used for treating memory dysfunction, such as, but not limited to 
cholinesterase inhibitors or memantine, are prohibited.   
8.8.5 Medications that can prolong the QT interval 
The use of medications that prolong the time from ECG Q wave to the end of the T wave or 
corrected T wave corresponding to electrical systole (QT/QTc interval) (see Section 17 Appendix 
D) is forbidden throughout the study. 

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9 
ASSESSMENT OF INVESTIGATIONAL MEDICINAL PRODUCT 
For patients already on PD medications at the time of randomization, all efficacy assessments 
must be done in the patient’s “OFF” state. No PD medication may be taken for at least 12 hours 
prior to any efficacy assessment. Study drug will be administrated on-site on visit days. 
Scales and questionnaires should be completed before dosing and before clinical procedures are 
performed by the study Investigator or other healthcare provider(s). Moreover, if possible, the 
patient completed instruments should be done prior to clinical interaction in order to try to 
minimize any influence this may have on the patient (either positive or negative). This includes 
the BDI-II, Patient Global Impression of Change (PGIC), Parkinson's Disease Questionnaire – 39 
(PDQ-39), EuroQol Five Dimensions Questionnaire (EQ-5D), and Health-Related Productivity 
Questionnaire (HRPQ). The remainder of the scales/questionnaires (MDS-UPDRS [including 
H&Y], PD-CRS, MoCA, Symbol Digit Modalities Test [oral] (SDMT), Trail Making Tests A 
(TMT-A), TMT-B, and CGI) will be administered by individuals who will be blinded to study 
treatment and who are trained in the administration of standardized questionnaires. 
The scales/questionnaires are provided in the appendices. Specific instructions for the 
administration of each scale/questionnaire are provided on each of the scales/questionnaires. 
9.1 
PRIMARY AND OTHER ENDPOINTS 
The MDS-UPDRS is a multimodal scale assessing both impairment and disability and is separated 
into 4 subscales (Parts I to IV) with a total summed score. The MDS-UPDRS includes 
components assessed by the certified blinded rater, as well as sections completed by the patient. 
Every effort should be made to have the same neurologist perform the ratings for a patient 
throughout the course of the study. 
• Part I: This assesses nonmotor experiences of daily living and is comprised of 
2 components:  
- 
Part IA contains 6 questions that are assessed by the certified blinded rater and focuses 
on complex behaviors.  
- 
Part IB contains 7 questions that are part of the self-administered Patient 
Questionnaire.  
• Part II: This assesses motor experiences of daily living. There are an additional 
13 questions that are also part of the self-administered Patient Questionnaire.  
• Part III: This assesses the motor signs of PD and is administered by the certified blinded 
rater.  
• Part IV: This assesses motor complications, dyskinesias, and motor fluctuations using 
historical and objective information. The certified blinded rater will complete this 
assessment at each visit for a patient on PD medication. 
Total score on the MDS-UPDRS is calculated by summing the 4 subscale scores. 

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9.1.1 Part 1: Dose escalation phase 
The primary endpoint in Part 1 is safety of each dose cohort. The following additional exploratory 
endpoints will be evaluated: 
• Change in MDS-UPDRS PART II+III score, performed during the OFF state, from 
baseline to 4 weeks. 
• Change in MDS-UPDRS PART II+III score, performed during the OFF state, from 
baseline to 8 weeks. 
• Change in MDS-UPDRS PART I+II+III, performed during the OFF state, from baseline to 
4 weeks. 
• Change in MDS-UPDRS PART I+II+III, performed during the OFF state, from baseline to 
8 weeks. 
The MDS-UPDRS will be performed by the certified blinded rater for all patients at screening, at 
Day 1, at Week 4 (Day 1), Week 8, and every 4 weeks thereafter, until completion. No PD 
medication may be taken for at least 12 hours prior to efficacy assessments. The maximum length 
of time a patient can be in Part 1 will be 50 weeks (or 66 weeks for Japanese patients), inclusive 
of the screening period.  
9.1.2 Part 2: Treatment phase 
The primary endpoint is the change in MDS-UPDRS (PART II+III score; Section 17 
[Appendix F], performed during the OFF state, from baseline to Week 52. Of note, Part IA, IB, 
and II of the MDS-UPDRS do not have separate ON or OFF ratings. The OFF definition provided 
in this protocol is to ensure uniformity among raters and the score sheets should document the 
OFF status associated with the Part III assessment.  
The MDS-UPDRS will be performed for all patients at screening, on Day 1, and at Weeks 13, 26, 
39, 52, 78, 104, 130, 156, 182, 208, and 216 by the certified blinded rater. No PD medication may 
be taken for at least 12 hours prior to efficacy assessments.  
Analysis of the change from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in the 4 subscale scores will be performed as an exploratory endpoint. 
9.2 
SECONDARY ENDPOINTS 
9.2.1 Part 1: Dose escalation phase 
Not applicable.   
9.2.2 Part 2: Treatment phase 
• Change in PD-CRS (total score) from baseline to Week 52. 
• Change in MDS-UPDRS PART I+II+III, performed during the OFF state, from baseline to 
Week 52.  
• Change in H&Y score from baseline to Week 52. 

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9.2.3 Scales and questionnaires (Part 1 and Part 2) 
The scales and questionnaires will be administered at designated study visits as shown in 
Section 1.3.1 (Part 1), and Section 1.3.2 (Part 2, Periods 1 and 2), and Section 1.3.3 (Part 2, 
Periods 3 and 4). 
9.2.3.1 Parkinson's disease-cognitive rating scale 
It has been suggested that impairment of the semantic memory and visuospatial functions, but not 
executive functions, predicts progression to dementia in PD. It is therefore relevant to identify 
those PD patients at risk of developing dementia by means of neuropsychological tools evaluating 
the whole spectrum of cognitive functions impaired over the course of the disease. The PD-CRS is 
a cognitive scale specifically designed to capture the whole spectrum of cognitive functions 
impaired over the course of PD (Section 17 [Appendix G]), specifically assessing 
fronto-subcortical and cortical cognitive functions. 
It comprises a total of 9 tasks explicitly designed for a brief and separate scoring of:  
• Frontal subcortical tasks (sustained attention, working memory, alternating and action 
verbal fluency, clock drawing, immediate, and delayed free recall verbal memory). 
• Posterior cortical tasks (confrontation naming and clock copying). 
Total scores on the PD-CRS are calculated by adding the subcortical and cortical PD-CRS scores. 
In Part 1, analysis of the change in PD-CRS total score and subscores from baseline to Week 8 
will be performed as an exploratory endpoint. The PD-CRS will be performed at screening, 
Day 1, and Week 8 by the certified blinded rater.  
In Part 2, analysis of the change in PD-CRS subscores from baseline to Week 52 and from 
baseline to Week 104, Week 156, and Week 208 will be performed as an exploratory endpoint. 
The PD-CRS will be performed for all patients at screening, Day 1, Weeks 13, 26, 39, 52, 78, 104, 
130,156, 182, and 208 by the certified blinded rater.  
9.2.3.2 Hoehn & Yahr scale 
The H&Y scale is a widely used clinical rating scale, which defines broad categories of motor 
function in PD (see Section 17 [Appendix F]). Among its advantages, it is simple and easy to 
apply. It captures typical patterns of progressive motor impairment which can be applied whether 
or not patients are receiving dopaminergic therapy. Progression in H&Y stages has been found to 
correlate with motor decline, deterioration in quality of life, and neuroimaging studies of 
dopaminergic loss.  
The scale allocates stages from 0 to 5 to indicate the relative level of disability. This scale is 
included within the MDS-UPDRS and will be completed for all patients.  
• Stage 0: No symptoms. 
• Stage 1: Symptoms on one side of the body only. 
• Stage 2: Symptoms on both sides of the body. No impairment of balance. 
• Stage 3: Balance impairment. Mild to moderate disease. Physically independent. 

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• Stage 4: Severe disability, but still able to walk or stand unassisted. 
• Stage 5: Wheelchair-bound or bedridden unless assisted. 
9.3 
SAFETY ENDPOINTS 
The observation period of safety endpoints will be divided into 3 segments: 
• 
The pretreatment period is defined as the time between the date of the informed consent 
up to the first administration of double-blind IMP. 
• 
The on-treatment period is defined as the period from the time of first IMP 
administration up to 6 weeks after the last administration of the IMP. 
• 
The post-treatment period starts on the day after the end of the on-treatment period. 
The baseline value for safety endpoints will be the last available value prior to the first 
administration of double-blind IMP. 
9.3.1 Part 1: Dose escalation phase  
Safety endpoints will be assessed by: 
• Physical examination. 
• Neurological examination. 
• Clinical laboratory evaluations, including hematology, biochemistry, and urinalysis. 
• Vital signs. 
• Assessment of AEs and concomitant medication. 
• Ophthalmological examination. Visual acuity and lens evaluation will be performed 
according to the Lens Opacity Classification System II (LOCSII) for monitoring potential 
cataract development. 
• Electrocardiogram. 
9.3.2 Part 2: Treatment phase 
Safety endpoints will be assessed by: 
• Incidence, relationship to study drug and resolution of treatment-emergent adverse events 
(TEAEs), SAE, TEAE/SAE leading to study drug or study discontinuation.  
• Ophthalmological examinations. Visual acuity and lens evaluation will be performed 
according to the LOCSII for monitoring potential cataract development. 

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9.3.3 Safety assessments (Part 1 and Part 2) 
9.3.3.1 Adverse events 
Refer to Section 10.4 to Section 10.7 for details. 
9.3.3.2 Laboratory safety variables 
All laboratory data listed in this section, except for CSF cell count, will be measured at a central 
laboratory. The laboratory data will be collected at designated visits as shown in Section 1.3. 
Clinical laboratory values will be analyzed after conversion into standard international units. 
International units will be used in all listings and tables. 
The following laboratory safety variables will be analyzed: 
• Hematology: red blood cell count, hematocrit, hemoglobin, white blood cell count with 
differential count (neutrophils, eosinophils, basophils, monocytes, and lymphocytes), 
platelets, prothrombin time (PT), partial thromboplastin time (PTT), and international 
normalized ratio (INR).  
• Biochemistry:  
- 
Plasma/serum electrolytes: sodium, potassium, chloride, calcium, bicarbonate; 
- 
Liver function: ALT, AST, gamma-glutamyl transferase (GGT), alkaline phosphatase 
(ALP), total and conjugated bilirubin; 
- 
Renal function: urea, serum creatinine; 
- 
Metabolism: glucose, albumin, total proteins; 
• Urinalysis (microscopy if determined to be medically necessary).  
• At screening, serum β-HCG test for WOCBP. 
9.3.3.3 Vital signs 
In Part 1, vital signs (including temperature, blood pressure, heart rate, and respiratory rate) will 
be collected at every visit (See Section 1.3.1). 
In Part 2, vital signs (including temperature, blood pressure, heart rate, and respiratory rate) will 
be collected at screening and at Weeks 0, 2, 4, 13, 26, 39, 52, 78, 104, 130, 156, 182, 208, and 
216. Vital signs will be collected for Japanese patients at Week 65, 91, 117,143, 169, and 195 in 
addition to the above time points (refer to Section 1.3.2 and Section 1.3.3). Orthostatic vital signs 
will be done at screening, Weeks 4 and 52; at all other time points, vital signs will be done in the 
supine position. 
Supine vital signs will be taken after patients have remained supine for 5 minutes. Orthostatic 
vital signs will be taken once after patients have remained supine for 5 minutes, and then again 
after 2 minutes in the standing position. Patients should move from supine to standing without 

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sitting in between vital sign measurements. Systolic/diastolic blood pressure and heart rate will be 
measured in each position. 
Body temperature (auricular or oral body temperature [Celsius °C]) will be collected using the 
same method for a given patient. Any fever (defined as: body temperature ≥38°C) should be 
recorded as an AE and the Investigator should perform all investigations necessary to rule out 
infection. 
Blood pressure will be measured under standardized conditions using the same method for a given 
patient. It will be determined at each study visit using a well calibrated apparatus. Both systolic 
and diastolic blood pressure must be recorded. 
9.3.3.4 Physical examination 
Whenever possible, the same physician should perform the physical examination at all study 
visits. The findings of each examination will be recorded.  
Each physical examination will include the following physical observations/measurements: 
general appearance; heart, skin, respiratory auscultation; head, eyes, ears, nose, and throat, 
extremities/joints, and abdomen. 
A site physician will assess the physical examination findings as normal, abnormal but not 
clinically significant, or abnormal and clinically significant. 
In Part 1, a physical examination will be performed at screening, Day 1, and Weeks 4 and 8, and 
if applicable, at Weeks 12, 16, 20, 24, 28, 32, and 36 and the completion visit. A physical 
examination will be collected for Japanese patients at Week 40, 44, 48, and 52 in addition to the 
above time points, if applicable (refer to Section 1.3.1). At screening, height will be measured 
without shoes and body weight will be measured without shoes or heavy clothing (See 
Section 1.3.1). 
In Part 2, a physical examination will be performed at screening, Day 1, and Weeks 26, 52, 104, 
156, 208, and 216. Any clinically significant abnormalities should be reported in the patient eCRF 
as medical history if observed at the screening visit (Day -60 to Day -1) or as an AE if observed 
during subsequent visits. Height will be measured at screening without shoes. Body weight will be 
measured without shoes or heavy clothing at screening and at Weeks 52, 104, 156, and 208 (See 
Section 1.3.2 and Section 1.3.3). 
9.3.3.5 Neurological examination 
Each neurological examination will include, but not be limited to, assessments of the patient’s 
mental status, cranial nerves, motor system (including muscle atrophy, tone and power), deep 
tendon reflex, sensation, and cerebellar function. The examination should be performed by the 
same neurologist throughout the study, if possible. 
When neurological and ophthalmological examinations are performed on the same day, the 
neurological examination should be performed before ophthalmological examination. 

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In Part 1, a neurological examination will be performed at screening, Day 1, and Weeks 2, 4, and 
8, and if applicable, at Weeks 12, 16, 20, 24, 28, 32, and 36, and the completion visit (See 
Section 1.3.1). A neurological examination will be collected for Japanese patients at Week 40, 44, 
48, and 52 in addition to the above time points, if applicable (refer to Section 1.3.1). 
In Part 2, a neurological examination will be performed at screening, Day 1, and Weeks 13, 26, 
39, 52, 78, 104, 130, 156, 182, 208, and 216 (See Section 1.3.2 and Section 1.3.3).  
9.3.3.6 Ophthalmological examination 
The full ophthalmological examination will include visual acuity, slit-lamp examination, and 
examination of the cornea, lens, and retina. The examination should include pupil dilation and 
evaluation of the lens according to the LOCSII. As part of the eye exam, a conventional 
confrontation visual field exam, such as the Donders’ test, can be performed by the local 
ophthalmologist as needed. Systematic visual field test by perimetry is not required for this trial.  
This evaluation should be accompanied by pictures of the lens for evaluation by the examining 
ophthalmologist. Photos of the lens will be reviewed/assessed by a central reader. 
In Part 1, a full ophthalmological examination and photography will be performed during 
screening, at Week 36 (or Week 52 for Japanese patients), if applicable, and at the completion 
visit, early withdrawal or treatment discontinuation, if applicable. At Week 4 only, and if 
applicable, at Weeks 12 and 28 (Week 36 for Japanese patients only), only best corrected visual 
acuity, slit lamp examination and fundoscopy without pupil dilation will be required; if a lens 
abnormality is found, the ophthalmologist at the site should perform pupil dilation and LOCSII 
evaluation, and document by photograph (see Section 1.3.1). Pupil dilation/full evaluation can be 
performed at any time if deemed medically necessary. 
In Part 2, a full ophthalmological examination will be performed during screening, Weeks 52, 
104, 156, 208, and early withdrawal or treatment discontinuation. For Weeks 4, 13, 26, 39, 78, 
130, 182, and 216, only best corrected visual acuity, slit lamp examination, and fundoscopy 
without pupil dilation will be required. In Part 2, if at any of the intermediate time points (Weeks 
4, 13, 26, and 39) or during Period 3, a lens abnormality is found, the ophthalmologist at the site 
should perform pupil dilation and LOCSII evaluation, and document by photograph (See  
Section 1.3.2 and Section 1.3.3). Pupil dilation/full evaluation can be performed at any time if 
deemed medically necessary. 
The examination should be performed by the same ophthalmologist throughout the study, if 
possible. Abnormal findings reported by the clinical sites will be reviewed by the DMC and/or the 
clinical site to adjudicate these findings as AESI and assess their seriousness/severity. 
9.3.3.7 Electrocardiogram (ECG) 
Heart rate, ECG recordings, including time from ECG Q wave to the end of the s wave 
corresponding to ventricular depolarization (QRS interval), the time from the onset of the P wave 
to the start of the QRS complex (PR interval), QT interval, ECG ST-segment deviation (ST 
deviation), T-wave morphology, and U-wave presence or absence will be determined per local site 
procedure using automated and manual readings of all ECGs. All ECG recordings will be 
centrally read by independent experts. Refer to central ECG reading manual for more details.  

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Any clinically significant abnormality (eg, corrected QT or QTc >450 msec in males/ >470 msec 
in females) observed at the first screening visit (Day -60 to Day -1) upon Investigator review will 
be immediately rechecked for confirmation before making a determination regarding patient 
exclusion from the study. Additional ECGs may be performed if deemed clinically necessary by 
the Investigator (eg, diagnosis of AE) and will be documented in the eCRF. 
In Part 1, a 12-lead ECG will be performed at screening, Day 1 (pre-dose and then 2, 4, and 
6 hours postdose), and Week 4, and if applicable, at Week 28 and at the completion visit 
(Section 1.3.1).  
In Part 2, an ECG will be performed at screening and Weeks 4, 26, 52, 104, 156, and 208 (See 
Section 1.3.2 and Section 1.3.3).  
9.4 
EXPLORATORY AND OTHER ENDPOINTS 
9.4.1 Pharmacodynamic and exploratory fluid biomarkers 
In Part 1 and Part 2, CSF samples collected by means of a LP and plasma samples will be 
collected at the times specified in the schedule of assessments (see Section 1.3).  
Pharmacodynamic biomarkers such as GL-1 and lyso-GL-1 in plasma and CSF, and GCase 
activity in dried blood spot will be measured at the Sponsor’s laboratory or at a subcontracted 
laboratory. Additional pharmacodynamic biomarkers, such as chitotriosidase, cytokines, 
ceramide, and sphingomyelin in plasma and serum or chitotriosidase and cytokines in CSF may 
also be assessed. See Section 17 (Appendix H) for a list of exploratory pharmacodynamic 
biomarkers per body fluid.  
Exploratory biomarkers to be evaluated may include: 
• 
NFL 
• 
α-Syn 
• 
beta amyloid (1-40, and 1-42) 
• Total tau and phospho-tau (181) 
Other variables may also be assessed if available data during the course of the study suggests a 
relationship to disease course in PD patients or to GZ/SAR402671. Markers related to PD and/or 
neurodegeneration and/or GZ/SAR402671 may be assessed at the Sponsor’s laboratory or at a 
contract research organization or an academic laboratory appointed by the Sponsor.   
The number of samples per patient is shown in Table 1.  

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Table 1 - Number of samples for pharmacodynamics assessment 
Type of Samples 
Plasma/Serum 
Cerebrospinal Fluid 
 
15 patients in 
Part 1 
12 Japanese 
patients 
216 patients 
in Part 2 
15 patients in 
Part 1 
12 
Japanese 
patients 
216 patients 
in Part 2 
Total number of sample 
timepoints by patienta 
3 
3 
7 
2 
2 
2 
Total number of samples for 
studya 
45 
36 
1512 
30 
24 
432 
a Approximate total number of samples.  
The assay methods will be detailed in a separate laboratory manual. 
9.4.2 Pharmacokinetics 
9.4.2.1 Sampling time 
The sampling times for blood and CSF collection in Part 1 and Part 2 can be found in the study 
flow charts (Section 1.4) and in a separate laboratory manual.  
Plasma and CSF collections for the same time points at Week 4 in Part 1 and at Week 52 in Part 2 
should be performed in as close succession as possible. 
Plasma parameters in Part 1 will include: 
• Day 1 (single dose administration): maximum plasma concentration observed (Cmax), tmax, 
and area under the plasma concentration versus time curve calculated using the trapezoidal 
method over a predefined time period (from time t= 0 to 24 hours [AUC0-24], and from t= 0 
to 48 hours [AUC0-48])  
• Week 2: plasma concentration observed just before treatment administration during 
repeated dosing (Ctrough) 
• Week 4: Ctrough, Cmax, tmax, AUC0-24, and apparent total body clearance of a drug at steady 
state after oral administration (CLss/F; calculated using the following equation: 
CLss/F = Dose/AUCτ, where τ is the dosing interval)  
• Week 8: Ctrough 
Cerebrospinal fluid parameters in Part 1 will include: 
• Day -14 to Day 1: pre-dose concentration 
• Week 4: Concentration at any time within 2 to 4 hours after administration of 
GZ/SAR402671 

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Plasma parameters in Part 2 will include: 
• Day 1 (single dose administration): Cmax, tmax, AUC0-24  
• Week 2: Ctrough 
• Week 26:  
- 
Ctrough 
- 
Concentration at any time within 2 to 4 hours after administration of GZ/SAR402671 
on visit day.  
• Week 52:  
- 
Ctrough 
- 
Concentration at any time within 2 to 4 hours after administration of GZ/SAR402671 
on visit day. 
Cerebrospinal fluid parameters in Part 2 will include: 
• Day -14 to Day 1: pre-dose concentration 
• Week 52 (all patients): Concentration at any time within 2 to 4 hours after administration 
of GZ/SAR402671 on visit day. 
The number of samples per patient is shown in Table 2.  
Table 2 - Number of samples for pharmacokinetics assessment 
Type of Samples 
Plasma 
Cerebrospinal Fluid 
 
15 
non-Japanese 
patients in 
Part 1 
12 Japanese 
patients in Part 1 
216 patients 
in Part 2 
15 
non-Japanese 
patients in 
Part 1 
12 Japanese 
patients in Part 1 
216 patients 
in Part 2 
Total number of sample 
timepoints by patienta 
15 
15 
11 
2 
2 
2 
Total number of 
samples for studya 
225 
180 
2376 
30 
24 
432 
a Approximate total number of samples. 
9.4.2.1.1 Lumbar puncture 
The LP will be performed by the site Investigator or another qualified clinician appointed by the 
Investigator.  
An LP for the collection of approximately 15 to 20 mL of CSF will be conducted for all patients 
per the visit schedule unless there is evidence of clinically significant coagulopathy or 
thrombocytopenia that would interfere with the safe conduct of the procedure. It is expected that 
all patients will undergo an LP at baseline. The baseline LP can be done within 14 days prior to or 
on the day of randomization (pre-dose). 

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The first 1 to 2 mL of CSF will be discarded; the subsequent 2 to 4 mL will be processed at the 
site’s local laboratory facility (unless the laboratory is not able to process the CSF within 4 hours) 
to conduct standard analyses on cell count, including red blood cell counts. The remaining CSF 
will be processed and shipped to a central laboratory for biomarker and PK assessments. Please 
refer to the laboratory manual provided by the central laboratory. 
Patients will be closely monitored during the procedure and following the procedure. 
9.4.2.2 Pharmacokinetics handling procedure 
Special procedures for collection, storage, and shipment of plasma and CSF samples collected for 
GZ/SAR402671 concentrations which will be provided in a separate laboratory manual provided 
by the central laboratory. 
An overview of PK sample handling procedure is provided in Table 3.  
Table 3 - Summary of plasma and cerebrospinal fluid samples collected for GZ/SAR402671 
concentrations 
Sample Type 
Plasma 
Cerebrospinal Fluid 
Sample volume 
2 mL blood 
0.5 mL 
Anticoagulant 
K2EDTA 
NA 
Handling procedures 
See study specific laboratory manual 
Aliquot split 
Yes (2) 
Storage conditions 
Keep in upright position at -70°C 
Shipment conditions 
Frozen, on dry ice 
Abbreviations: K2EDTA: dipotassium ethylenediamine tetra-acetic acid; NA: not applicable. 
9.4.2.3 Bioanalytical method 
Bioanalytical analyses will be performed under the responsibility of the central laboratory. Only 
samples from patients on active study treatment will be analyzed.  
Plasma GZ/SAR402671 concentrations will be determined using a validated liquid 
chromatography tandem mass spectrometry method (DMPK15-R012) with a lower limit of 
quantification of 0.500 ng/mL. 
Cerebrospinal fluid concentrations of GZ/SAR402671 will be determined using a validated liquid 
chromatography tandem mass spectrometry method (DMPK15-R016) with a lower limit of 
quantification of 0.100 ng/mL. 

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9.4.2.4 Pharmacokinetic parameters 
The following PK plasma parameters will be calculated, using noncompartmental methods from 
plasma GZ/SAR402671 concentrations obtained after single dose administration. The parameters 
will include, but may not be limited to the following: 
 
Parameters 
Drug/Analyte 
Definition/Calculation 
Cmax 
GZ/SAR402671 
Maximum plasma concentration observed 
Ctrough 
GZ/SAR402671 
Plasma concentration observed just before treatment administration during 
repeated dosing 
tmax 
GZ/SAR402671 
Time to reach Cmax 
AUC0-24 or  
AUC 0-48  
GZ/SAR402671 
Area under the plasma concentration versus time curve calculated using 
the trapezoidal method over a predefined time period (from time t= 0 to 
24 hours; AUC0-24, and from t= 0 to 48 hours; AUC0-48) 
AUC 
GZ/SAR402671 
Area under the plasma concentration versus time curve extrapolated to 
infinity according to the following equation:  
z
C
AUC
AUC
last
last

+
=
 
Values with percentage of extrapolation >30% will not be reported 
t1/2z 
GZ/SAR402671 
Terminal half-life associated with the terminal slope (λz) determined 
according to the following equation: 
z
1/2Z
0.693
 
t

=
 
where λz is the slope of the regression line of the terminal phase of the 
plasma concentration versus time curve, in semilogarithmic scale. Half-life 
is calculated by taking the regression of at least 3 points. 
CLss/F 
GZ/SAR402671 
Apparent total body clearance of a drug at steady state after oral 
administration; calculated using the following equation: 
CLss/F = Dose/AUCτ, where τ is the dosing interval 
Exploratory GZ/SAR402671 metabolite PK profiling and/or metabolite exposure analysis may be 
conducted in the collected plasma PK and CSF samples during Part 1 and Part 2 of the study. 
9.4.3 Dopamine transporters scan assessment 
DAT scans will be performed only in countries where it is approved. 
Women of childbearing potential must have a urine (or serum if required by the site) pregnancy 
test prior to injection of DAT scan. The result must be confirmed as negative prior to proceeding 
with the injection.  

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Before the DAT scan injection, patients will be pretreated with stable iodine (10 drops of a 
saturated solution of potassium iodide) to reduce the uptake of DAT scan by the thyroid, 
according to the local regulation.  
Patients will be injected with 3 to 5 mCi of DAT. Within a 4-hour (±30 minutes) window 
following the injection, patients will undergo standard brain single-photon emission computerized 
tomography imaging as per the Society of Nuclear Medicine Practice Guidelines. 
A central reading center will be used to read the imaging from the patients to ensure consistency 
and accuracy between sites.  
In Part 1, patients will undergo a DAT scan within 7 days prior to randomization (Day -7 to 
Day -1) or on the day of randomization (Day 1, pre-dose) (See Section 1.3.1).  
In Part 2, patients will undergo a DAT scan at screening (within 7 days prior to randomization 
[Day -7 to Day -1] or on the day of randomization [Day 1, pre-dose]) and Weeks 52, 104, 156, 
and 208 (See Section 1.3.2 and Section 1.3.3).  
9.4.4 Levodopa or other Parkinson’s disease therapy 
9.4.4.1 Time to initiation/intensification of levodopa/PD therapy 
It is anticipated that GBA-PD patients, if entering the study on a PD medication, will be able to 
remain on a stable dose of the PD medications for the entire duration of the study. However, it 
may be considered necessary in the medical judgment of Investigator to initiate or intensify PD 
medications. In such occurrence, this could apply only to an immediate release levodopa 
formulation. If PD medications are to be initiated or intensified, patients will be asked to return 
for an additional study visit on site. This also holds true if a patient requires a change in his/her 
PD medication. The Investigator will document any new medications or changes in medication at 
each study visit on the Concomitant Medication Log. 
In Part 2 only, time to initiation of levodopa or other PD therapy (for patients not on 
levodopa/other PD therapy at baseline) or to increased dose of levodopa/other PD therapy (for 
patients on levodopa/other PD therapy at baseline) will be calculated.  
9.4.4.2 Reduction of levodopa/PD therapy 
In Part 2 only, there might be a possibility that GBA-PD patients, if entering the study on a PD 
medication, would be able reduce their dose of the PD medication. If PD medications are to be 
reduced or stopped, the Investigator will document these changes in medication at each study visit 
on the Concomitant Medication Log. 

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9.4.5 Scales and questionnaires 
9.4.5.1 Montreal cognitive assessment score 
In early PD, when cognitive deficits occur, they are subtle and mild and the patients usually 
perform in the normal range on the widely used Mini Mental State Examination. The MoCA is a 
rapid screening instrument like the Mini Mental State Examination but was developed to be more 
sensitive to patients presenting with mild cognitive complaints. It assesses short-term and working 
memory, visuospatial abilities, executive function, attention, concentration, language, and 
orientation. The total score ranges from 0 to 30 (see Section 17 [Appendix I]). This assessment 
will be scored by an independent blinded rater. 
In Part 1, the changes from baseline to Week 8 in MoCA score will be assessed, separately for 
Japanese and non-Japanese patients. 
In Part 2, the changes in MoCA score from baseline to Week 52 and from baseline to Week 104, 
Week 156, and Week 208 will be assessed. 
9.4.5.2 Oral symbol digit modalities test score  
The SDMT assesses divided attention, visual scanning, and motor speed. After being presented 
with a coding key, the patient is required to pair the number with the corresponding symbol as 
rapidly as possible and within 90 seconds (see Section 17 [Appendix J]). Symbol Digit Modalities 
Test requires the subject to substitute a number for its corresponding geometric figure. There are 9 
figures. On the record form, there are a series of rows containing geometric figures in the top half, 
but the bottom half is left blank. When it is clear that the subject understands the task, he or she is 
told to fill in the remaining boxes as quickly as possible, completing one box at a time, one row at 
a time, before proceeding to the next. Skipping from box to box with the same geometric figure is 
not permitted. Subjects receive one point for each correctly completed box. The total score is the 
total number of correctly completed boxes in the time allowed. The practice items are not counted 
in the scoring. This assessment will be scored by an independent blinded rater. 
The test can be administered by having the subject write out the correct response or by having the 
subject report the correct answer (ie, number) aloud. Higher scores are better scores and the range 
of scores can be from 0 to 110 for SDMT oral scores. 
Parkinson’s disease patients have motor skill deficits, therefore oral SDMT will be used in this 
study as this version has greater sensitivity than the written version. The blinded rater will read 
the instructions to the patient, point to the open spaces on the form and record the answer from the 
patient.   
In Part 1, the changes from baseline to Week 8 in SDMT oral score will be assessed, separately 
for Japanese and non-Japanese patients.  
In Part 2, the changes in SDMT oral score from baseline to Week 52 and from baseline to 
Week 104, Week 156, and Week 208 will be assessed. 

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9.4.5.3 Trail making test A and B score 
The TMTs are popular neuropsychological instruments used either alone as a screening 
instrument for detecting neurological disease and neuropsychological impairment or as part of a 
larger battery of tests. The tests are believed to measure the cognitive domains of processing 
speed, sequencing, mental flexibility, and visual–motor skills (see Section 17 [Appendix K]). It 
consists of two parts in which the patient is instructed to connect a set of 25 dots as quickly as 
possible while still maintaining accuracy. The test can provide information about visual search 
speed, scanning, speed of processing, mental flexibility, as well as executive functioning. It is 
sensitive to detecting cognitive impairment associated with dementia. This assessment will be 
scored by an independent blinded rater. 
Scoring will include total score for each TMT-A and TMT-B as well as the change in the 
difference between TMT-B score minus TMT-A score. 
In Part 1, the changes from baseline to Week 8 in TMT-A and TMT-B score including the change 
in the difference between TMT-B minus TMT-A score will be assessed, separately for Japanese 
and non-Japanese patients.   
In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in TMT-A and TMT-B score including the change in the difference between TMT-B 
minus TMT-A score will be assessed. 
9.4.5.4 Beck depression inventory, second edition  
Depression will be monitored during the study by using the BDI-II; see Section 17 (Appendix L). 
Beck Depression Inventory, second edition is a 21-question, multiple-choice, self-report 
inventory. It is composed of items relating to symptoms of depression such as hopelessness and 
irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms 
such as fatigue, weight loss, and disinterest in sex. 
The wording of the BDI-II is clear and concise. The test contains 21 items, most of which assess 
depressive symptoms on a Likert scale of 0-3. The two exceptions to this are questions 16 and 18. 
Question 16 addresses changes in sleeping pattern, while question 18 addresses changes in 
appetite. Patients will be asked to report their own feelings over the past 2 weeks instead of 
1 week, as in the BDI and BDI-IA. The reason for this is to be consistent with the Diagnostic and 
Statistical Manual of Mental Disorders, 4th Edition criteria for depression. There were also two 
items added to indicate any directional changes in eating and sleeping patterns. Finally, all forms 
of the inventory are written at the 5th grade reading level. 
Clinical interpretation of scores is accomplished through criterion-referenced procedures utilizing 
the following interpretive ranges: total BDI-II scores of 0-13 indicate minimal depression, scores 
of 14-19 indicate mild depression, scores of 20-28 indicate moderate depression, and scores of 
29-63 indicate severe depression. The BDI-II will be performed at every study visit in this trial. 

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If a patient has a score of ≥20 or if the patient has a score <20 but answers “yes” to answer 2 or 
3 of question 9, the patient must be referred to their health care professional for psychiatric 
evaluation. This will be captured as an AE. The participant may continue the study, but this is 
dependent on the judgment of the PI.  
In Part 1, BDI-II will be administered at every study visit, except on Visits 3 and 4 (Week 0, 
Days 2 and 3) and Visit 7 (Week 4, Day 2).  
In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in BDI-II score will be assessed. 
9.4.5.5 Clinical global impression scale 
The CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global 
improvement or change (CGIC), and therapeutic response (see Section 17 [Appendix M]). Each 
component of the CGI is rated separately; the instrument does not yield a global score. CGI will 
be scored by an independent blinded reader.  
The CGIS is rated on a 7-point scale, with the severity of illness scale using a range of responses 
from 1 (normal) through to 7 (amongst the most severely ill patients). CGIC scores range from 
1 (very much improved) through to 7 (very much worse). Treatment response ratings should take 
account of both therapeutic efficacy and treatment-related AEs and range from 0 (marked 
improvement and no side effects), and 4 (unchanged or worse and side-effects outweigh the 
therapeutic effects).  
In Part 1, CGI scores will be assessed on Day 1 and Week 8, separately for Japanese and 
non-Japanese patients.   
In Part 2, CGI scores will be assessed on Day 1 and Week 52.  
9.4.5.6 Patient global impression of change scale 
In 2004, Hurst and Bolton describe the PGIC scale as a more meaningful measure of health care 
system performance via direct feedback from the patient. The PGIC is particularly suited to 
capturing clinically meaningful change that makes a difference to the patient and has been used 
extensively in studies of musculoskeletal conditions. 
This questionnaire (see Section 17 [Appendix N]) will be administered by individuals trained in 
the administration of standardized questionnaires. Score result should not be disclosed to the 
blinded rater.  
In Part 1, PGIC will be administered on Week 8.   
In Part 2, PGIC will be administered on Weeks 13, 26, 39, and 52.  

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9.4.5.7 Parkinson's disease questionnaire – 39 score 
The PDQ-39 is a self-completion patient-reported outcome designed to address aspects of 
functioning and well-being over the last month for those affected by PD (see Section 17 
[Appendix O]). This patient-reported outcome assesses how often patients experience difficulties 
across different quality of life dimensions: 
• Mobility (10, #1-10); 
• Activities of daily living (6, #11-16); 
• Emotional well-being (6, #17-22); 
• Stigma (4, #23-26)  
• Social support (3, #27-29); 
• Cognition (4, #30-33); 
• Communication (3, #34-36); 
• Bodily discomfort (3, #37-39). 
Moreover, the PDQ-39 assesses impact of PD on specific dimensions of functioning and 
well-being, with a lower score reflecting a better quality of life. 
In Part 1, the changes from baseline to Week 8 in PDQ-39 will be assessed, separately for 
Japanese and non-Japanese patients.  
In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in PDQ-39 scores will be assessed. 
9.4.5.8 EuroQol five dimensions questionnaire  
The EQ-5D is a standardized instrument for measuring generic health status. The health status 
measured with EQ-5D is used for estimating preference weight for that health status, then by 
combining the weight with time, quality-adjusted life year can be computed (see Section 17 
[Appendix P]).The EQ-5D is made up for two components; health state description and 
evaluation. In the description part, health status is measured in terms of five dimensions (5D); 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension 
asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress 
by oneself, and usual activities dimension measures performance in "work, study, housework, 
family or leisure activities". In pain/discomfort dimension, it asks how much pain or discomfort 
they have, and in anxiety/depression dimension, it asks how much anxious or depressed they are. 
The respondents self-rate their level of severity for each dimension using a five-level scale. In the 
evaluation part, the respondents evaluate their overall health status using the visual analogue 
scale. 
In Part 1, the changes from baseline to Week 8 in EQ-5D score will be assessed, separately for 
Japanese and non-Japanese patients.  

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In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in EQ-5D scores will be assessed. 
9.4.5.9 Falls efficacy scale 
The Falls Efficacy Scale (FES) is used to assess perception of balance and stability during 
activities of daily living and to assess the patient’s fear of falling (see Section 17 
[Appendix Q]). It is a 10-item questionnaire designed to assess confidence in a person’s ability to 
perform 10 daily tasks without falling as an indicator of how one's fear of falling impacts physical 
performance. Each item is rated from 1 ("very confident") to 10 ("not confident at all"), and the 
per item ratings are added to generate a summary total score. Total scores can range from 10 (best 
possible) to 100 (worst possible). Thus, lower scores indicate more confidence and higher scores 
indicate lack of confidence and greater fear of falling. Of note, the FES appears to be a reliable 
and valid method for measuring fear of falling. This scale has excellent reliability, is correlated 
with measures of balance and gait, and predicts future falls and decline in functional capacity. 
Most importantly, the FES has proven sensitive to change in fears following clinical interventions. 
In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in FES scores will be assessed. FES will be administered at baseline, Weeks 13, 26, 39, 
52, 78, 104, 130, 156, 182, and 208. 
9.4.6 Parkinson’s disease progression model 
The data collected during the study will be used to develop a Parkinson’s disease progression 
model in early-stage PD patients carrying a GBA mutation. 
9.5 
HEALTH-RELATED PRODUCTIVITY QUESTIONNAIRE 
Health-related quality of life measures are currently essential for the evaluation of patients in 
clinical trials. Patients with PD are particularly vulnerable to deterioration of health-related 
quality of life resulting from significant motor disability and the burden of nonmotor symptoms. 
Assessment of health-related quality of life of persons with PD is thus of essential importance. 
The HRPQ contains items related to productivity during paid work, but more importantly for this 
population, it also has questions about ability to be productive in the home at household chores 
(cooking, cleaning, gardening, repairs, etc) (see Section 17 [Appendix R]). 
In Part 1, the changes from baseline to Week 8 in HRPQ scores will be assessed, separately for 
Japanese and non-Japanese patients.  
In Part 2, the changes from baseline to Week 52 and from baseline to Week 104, Week 156, and 
Week 208 in HRPQ scores will be assessed. 

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9.6 
PHARMACOGENETIC ASSESSMENT 
During the screening period, 1 blood sample will be collected for investigation of GBA mutations 
and the LRRK2 G2019S mutation, which is required to include patients in the study (see 
Section 17 Appendix A).  
Approximately 6 to 10 mL whole blood will be collected for pharmacogenetic analysis during the 
screening period. Special procedures for collection, storage, and shipping of DNA samples for 
investigation of GBA mutations will be described in detail in the laboratory manual provided to 
the study sites. 
Once these analyses have been performed, all DNA material left over will be destroyed 
(Section 9.6.1).  
9.6.1 Optional stored DNA sample (not applicable in Israel) 
Once enrollment is confirmed, patients will be asked if they are willing to consent to long-term 
storage of DNA samples for future use. For those patients who signed the optional 
Pharmacogenetic Informed Consent Form, a blood sample will be collected as specified in the 
study flow chart (Section 1.3.1) for the purpose of additional pharmacogenetic analysis and this 
sample will be stored.  
In Part 2, patients who initially consented, will be asked if they consent for a second blood 
sample. This sample will be collected at Week 52 or at any visit after Week 52. 
The data from patient’s genetic material may be used to understand PD disease pathogenesis, 
GZ/SAR402671 signaling, drug response or activity and toxicity, to determine a possible 
relationship between the genes and PD or diseases, to develop and/or validate a bioassay method, 
possibly to identify new drug targets or biomarkers, and investigate allelic variants of drug 
metabolizing enzymes (DMEs) and/or drug transporters. In addition, as new scientific knowledge 
is gained that may be related to GZ/SAR402671, patient response or association with PD, other 
genes may also be studied. 
This blood sample will be transferred to a Sanofi site (or a subcontractor site) which could be 
located outside of the country where the study is conducted. Sanofi or its subcontractor will 
extract DNA from the sample.  
This blood sample, and the DNA that is extracted from it, will be assigned a second number, a 
Genetic ID that is different from the Patient ID. This “double coding” is performed to separate a 
patient’s medical information and DNA data.  
The clinical study data (coded by Patient ID) will be stored in the clinical data management 
system (CDMS), which in a distinct database in a separate environment from the database 
containing the genetic data (coded by Genetic ID). The key linking Patient ID and Genetic ID will 
be maintained by a third party, under appropriate access control. The matching of clinical data and 
pharmacogenetic data, for the purpose of data analysis, will be possible only by using this key, 

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which will be under strict access control. All data will be reported only in coded form in order to 
maintain confidentiality.  
The DNA will be stored for up to 15 years from the completion of the clinical study report.  
If a patient, via written request, asks for destruction of his/her samples and the samples have not 
yet been double coded, the Sponsor will destroy the samples per applicable guidelines; however, 
any data already generated will not be destroyed. The Sponsor will notify the Investigator in 
writing that the samples have been destroyed. However, any analyses of the sample(s) that have 
already been performed or data generated prior to patient’s request will continue to be used as part 
of the research in this project and will be kept by the Sponsor. 
Special procedures for collection, storage, and shipping of DNA samples are summarized in 
Table 4 and will be described in detail in the laboratory manual provided to the study sites. 
Table 4 - Summary of handling procedures for stored DNA samples 
Sample Type(s) 
Pharmacogenetics 
Blood sample volume 
Up to 8.5 mL 
Tube type 
Tube provided by central laboratory for DNA sample storage 
Anticoagulant 
See laboratory manual for specific instructions 
Blood handling procedures 
Shipping conditions 
See laboratory manual for specific instructions 
See laboratory manual for specific instructions 
DNA storage conditions 
70° C or colder; may also be placed temporarily on dry ice (only 
if the sample is being shipped frozen) 
Abbreviation: DNA: deoxyribonucleic acid. 
9.7 
FUTURE USE OF NON-GENOMIC SAMPLES 
Not all of the samples collected during this study may be required for the tests planned in this 
clinical trial. For patients who have consented to it, the samples that are unused or left over after 
testing may be used for other research purposes (excluding genetic analysis) related to PD and/or 
to GZ/SAR402671 other than those defined in the present protocol, as per local regulations.  
These other research analyses can help to better understand PD disease pathogenesis, 
GZ/SAR402671 signaling, drug response or activity, and toxicity, to develop and/or validate a 
bioassay method, and possibly to identify new drug targets or biomarkers.  
These samples (excluding genetic analysis and long-term stored DNA sample) will remain 
labelled with the same identifiers as the one used during the study (ie, Patient ID). They will be 
transferred to a Sanofi site (or a subcontractor site) which can be located outside of the countries 
where the study is conducted and stored for up to 5 years and as per local regulations. The 
Sponsor has included safeguards for protecting patient confidentiality and personal data (see 
Section 14.3 and Section 14.5).  

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If a patient, via written request, asks for destruction of his/her research samples, the Sponsor will 
destroy the samples per applicable guidelines; however, any data already generated will not be 
destroyed. The Sponsor will notify the Investigator in writing that the samples have been 
destroyed. However, any analyses of the sample(s) that have already been performed or data 
generated prior to patient’s request will continue to be used as part of the research in this project 
and will be kept by the Sponsor. 

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10 
STUDY PROCEDURES 
In order to ensure proper evaluation of efficacy, the staff of each study center will include the 
following physicians: a primary treating neurologist, a neurologist Sub-Investigator and a 
minimum of 2 blinded examining neurologist/raters. The primary treating neurologist, who can 
serve as the PI, will have overall responsibility to lead the site study team (physicians, 
pharmacists, technicians, nurses, and clinical coordinators) in all aspects of the study. The primary 
treating neurologist/PI will also have a neurologist Sub-Investigator who can back up the PI 
when/if needed. The blinded examining neurologist/raters must be experienced neurologists, or 
qualified non-physician health professionals who meet a predetermined level of experience in 
evaluating GBA-PD patients including examining GBA-PD patients and scoring the various 
scales when permitted by local laws, health authority rules, and ethics committee requirements. 
This delineation assures that AEs or other health issues for any patient do not influence the 
neurological assessment. Both the treating neurologist and blinded examining neurologist/ rater 
must have a minimum of 2 years of PD clinical experience.  
Treating neurologist 
The treating neurologist will be responsible for evaluation of patient eligibility; supervision of 
IMP administration; assessing and treating of AEs; assessing, confirming, and managing any 
GBA-PD issues; and monitoring of safety assessments, including routine laboratory results and 
concomitant medications. As much as possible, the same treating neurologist, be it the PI or 
Sub-Investigator, must maintain that role for a given patient throughout the study. 
Examining neurologist/blinded rater  
Every effort should be made to maintain the same blinded raters throughout the study. In case the 
rater must change, new blinded raters must be trained and remain throughout the duration of the 
study. For a given patient, one blinded rater does not have to perform all the assessments. 
However, each questionnaire (MDS-UPDRS [including H&Y], PD-CRS, MoCA, SDMT [oral], 
TMT-A, TMT-B, and CGI) should be scored by the same blinded rater throughout the study.  Of 
note, only MDS-UPDRS and PD-CRS require a certified blinded rater. 
The examining neurologist/blinded rater will be responsible for conducting all the efficacy 
assessments and for determining the scores, and must be certified for MDS-UPDRS and PD-CRS 
rating prior to any involvement in the study. Throughout the study, the examining 
neurologist/rater must not be involved with any other aspect of patient care and management and 
must remain blinded to the patient’s treatment and safety profile (AEs, concomitant medications 
and laboratory results). Moreover, he/she must also not read the protocol, ensuring accurate rater-
blinded assessments. This person should instead refer to the schedule of assessments.  
All other investigational site staff must refrain from discussing any aspects of the protocol and/or 
safety issues with the examining neurologist. The examining neurologist/blinded rater should 
maintain the role for a given patient throughout the study. The study site is responsible for 
appointing a backup examining neurologist/rater in the case the primary is unable to fulfill the 

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role and that person is responsible for conducting the remainder of the assessments for the 
patient throughout the remainder of the study. The role of the treating neurologist and the 
examining neurologist is NOT interchangeable throughout the study even for different patients.  
The Clinical Coordinator may be a nurse or physician who will be responsible for coordinating 
and assisting all study site staff, including patient scheduling and completion and monitoring of 
all patients’ case report forms. He/she will be responsible for coordinating IMP administration, 
and collect, process, and send all blood and other forms of biological samples and requests to the 
central laboratory. Additionally, he/she will be responsible for administering the patient-reported 
questionnaires, and coordinating the conduct of the baseline MRI (without contrast). 
10.1 
VISIT SCHEDULE 
This is an outpatient study consisting of on-site visits. Additional, optional phone-call visits to 
monitor safety should be scheduled as often as deemed necessary by the Investigator. If a patient 
does not attend a scheduled visit, the study site personnel should contact the patient as soon as 
possible for rescheduling.  
For patients already on PD medications at baseline, the H&Y scale must be done in the patient’s 
“ON” state (see inclusion criterion I 05). For patients already on PD medications at the time of 
randomization, all efficacy assessments, and all scales and questionnaires must be done in the 
patient’s “OFF” state. Therefore, PD medication cannot be taken for at least 12 hours prior to the 
visits including efficacy assessment. Study drug will be administrated on-site on visit days.   
Scales and questionnaires should be completed before dosing and before clinical assessments by 
the Study Investigator or other healthcare provider(s) are performed. At least two trained raters 
should be available at each site at all times.   
When neurological and ophthalmological examinations are performed on the same day, the 
neurological examination should be performed before ophthalmological examination.  
Before any screening assessment is performed, information regarding the aims and methods of the 
study, its constraints and risks will be explained to the patient and a written summary in the form 
of an informed consent will be provided. The patient must sign and date the informed consent 
before screening and before patient demography is recorded. 
Although the screening assessments for this study are grouped under the heading of a single visit 
in this protocol, it is possible for these to be performed over more than one site visit if necessary, 
as long as the screening visit window prior to Day 1 (Visit 2) is respected. Rescreening is possible 
in this study, see Section 7.2.3.  
Further details of procedures/assessments listed in the following sections are captured in the study 
flow charts (Section 1.3). 

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10.1.1 Part 1: Escalated dose phase 
Visit window: The randomization visit (Day 1) can be performed within 60 days from the 
screening visit. Using Day 1 as reference, a time frame of ±3 days is acceptable for Visits 5 to 9 in 
Part 1. (If one visit date is skipped/missed/changed, the next visit should take place according to 
the original schedule).  
10.1.1.1 Visit 1: Screening from Day -60 to -1 
The following activities will be performed: 
• An explanation of the purpose, procedures, potential risks, and benefits of this study will 
be provided to the patient. 
• Informed consent signature and date will be collected. 
• A patient diary will be issued with instructions to record any safety issues, and if the 
patient is eligible, missing doses will also be collected after randomization. The patient 
should bring their diary and any remaining capsules to each clinic visit. The site staff will 
review the patient diary during each clinic visit and record excursions from treatment into 
the eCRF. The patient diary will be retrieved when the patient finishes their participation 
in the study. 
• One blood sample will be collected for investigation of GBA mutations required to include 
patients in the study (see Section 9.6). See Section 17 (Appendix A) for a list of GBA 
mutations. This gene will be sequenced even if historical results are available. Also, this 
sample will be investigated for a specific mutation in the LRRK2  
• gene (G2019S) and patients carrying this mutation will be excluded. Of note, if patient 
meets these two criteria, then the screening visit may proceed for all other items 
described below. 
• Patient demography will be recorded. 
• BDI-II (Appendix L): At screening, patients with BDI-II of 20-28, inclusive, should be 
evaluated by a mental health specialist before the Investigator can determine if the patient 
would be able to fully participate in the trial. Patients with a BDI-II of >28 (severe 
depression) at screening will be excluded. 
• Confirmation of eligibility by the Investigator. 
• GBA complete gene sequencing and LRRK2 G2019S genotyping.  
• Medical/surgical history and PD history. 
• Review of prior medications. 
• Confirmation of diagnosis of RBD (historically documented polysomnography or RBD 
screening questionnaire [Appendix B]). 
• Physical examination. 
• General neurological examination. 

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• Record of height and body weight measurements. 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C). 
• 12-lead ECG. 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: Complete blood count (CBC), with differential and platelet count; 
coagulation profile: PT, PTT, and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Serum β-HCG pregnancy test (for WOCBP). 
• Full ophthalmology examination and photography. 
• Review of current medical conditions, with AE/SAE reporting (if any). 
• GCase activity: dried blood spot from whole blood sample for genetic testing. 
• MDS-UPDRS (Appendix F). 
• Hoehn and Yahr (Appendix F); for patients on a stable dose of PD medication, this should 
be done in the “ON” state. 
• PD-CRS (Appendix G). 
• MoCA (Appendix I). 
If patients demonstrate eligibility based on all previous screening criteria:  
• MRI (without contrast) scan will be performed (at least 7 days prior to the end of the 
screening period [Day -8]). 
• LP for collection of CSF will be performed (within 14 days prior to randomization or at 
Day 1, pre-dose).  
• DAT scan will be performed (within 7 days prior to randomization or at Day 1, pre-dose). 
10.1.1.2 Visit 2: Randomization/baseline at Week 0/Day 1 
Baseline assessments will be completed within the 60-day screening period. Eligibility will be 
reconfirmed prior to randomization/first dose administration on Day 1.  
Patients will receive either placebo or GZ/SAR402671, orally, at the clinic.  
In addition to recording any safety issue, the patient diary will also be used to record any missing 
doses after randomization.  The patient should bring their diary and any remaining capsules to 
each clinic visit. The site staff will review the patient diary during each clinic visit and record 

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excursions from treatment into the eCRF. The patient diary will be retrieved when the patient 
finishes their participation in the study.  
For Japan only (Appendix T), patients should be hospitalized for Visit 2 through 4, in principle; 
however, if hospitalization does not occur, the Investigator should follow up each day with a 
phone call to check if the patients experience any AEs (patients living alone must be hospitalized 
for Visit 2 through 4). 
The baseline visit (Day 1) will include assessments and activities as listed in the study flow chart, 
Section 1.3.1, which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator:  
- 
BDI-II (Appendix L) 
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
• Reconfirmation of eligibility by the Investigator 
• Review of concomitant medications 
• Randomization via IVRS 
• 12-lead ECG (at pre-dose and then at 2 hours, 4 hours, and 6 hours postdose) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G)   
• Other questionnaires and scales:  
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
- 
CGI (Appendix M) 
• Physical examination 
• General neurological examination 
• Archival blood sample collected prior to the start of IMP 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 

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- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analysis 
• Blood sampling for PK analysis at multiple time points: at pre-dose and at 1, 2, 4, and 
8 hours after IMP intake 
• Pharmacogenetics DNA sample (optional; not applicable in Israel [Appendix T]) 
• DAT scan (only if not performed during the screening period, pre-dose) 
• Lumbar puncture for collection of CSF (if not already done during the screening period) 
for biomarker and PK analyses  
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day. 
10.1.1.3 Visit 3: Week 0/Day 2 
Patients will not receive IMP on Day 2 (drug holiday), in order to better characterize the PK of the 
IMP, and will have a blood sample for PK analysis collected at 24 hours after first IMP intake.   
The following assessments should be done as listed in the study flow chart, Section 1.3.1, in the 
following order: 
• Review of concomitant medications 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK analysis (24 hours post-Day 1 dose PK sample; Section 1.4.1) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 

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10.1.1.4 Visit 4: Week 0/Day 3 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.1: 
• Review of concomitant medications 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK analysis (48 hours post-Day 1 dose PK sample or 1 hour before 
dosing; Section 1.4.1) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.1.5 Visit 5: Week 2 (±3 days) 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• General neurological examination 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C)  
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Blood sampling for biomarker analysis 
• Blood sampling for PK analysis (1 hour before dosing) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 

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Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.1.6 Visit 6: Week 4/Day 1 (±3 days) 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• MDS-UPDRS, including H&Y (Appendix F) 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• Physical examination 
• General neurological examination 
• Visual acuity check, slit lamp examination and fundoscopy without pupil dilation 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK at multiple time points (pre-dose, 1, 2, 4, and 8 hours after IMP 
intake) and biomarker analyses 
• Lumbar puncture for collection of CSF for PK and biomarker analyses 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 

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10.1.1.7 Visit 7: Week 4/Day 2 (±3 days) 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK (24 hours post-Week 4/Day 1 dose PK sample or 1 hour before 
dosing; Section 1.4.1) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.1.8 Visit 8: Week 8 (±3 days) 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PGIC (Appendix N)  
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
- 
MDS-UPDRS, including H&Y (Appendix F) 
- 
PD-CRS (Appendix G) 
• Other questionnaires and scales   
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
- 
CGI (Appendix M) 
• Review of concomitant medications 
• Physical examination 
• General neurological examination 

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• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK analyses (1 hour before dosing) 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.1.8.1 Visits 8.1 – 8.7 (Visits 8.8-8.11 for Japanese patients only): Weeks 12-36 
(Weeks 40-52 for Japanese patients only) (±3 days) 
This visit must be repeated for all ongoing patients every 4 weeks until all patients from Cohort 3 
complete Part 1. A maximum of 36 weeks of treatment will be allowed (applicable to patients in 
Cohort 1), ie, up to 7 additional visits (8.1-8.7) may be required. In Japan (Appendix T), a 
maximum of 52 weeks of treatment will be allowed (applicable to patients in Cohort 1), ie, up to 
11 additional visits (8.1-8.11) may be required. 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• MDS-UPDRS, including H&Y (Appendix F) 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• Physical examination 
• General neurological examination 
• Visual acuity check, slit lamp examination and fundoscopy without pupil dilation only at 
Weeks 12 and 28 (Week 36 for Japanese patients), if applicable 
• Full ophthalmology examination and photography at Week 36 (or Week 52 for Japanese 
patients), if applicable 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• 12-lead ECG; Week 28, if applicable 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 

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• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
10.1.1.9 Visit 9: Safety follow-up completion visit (±3 days) 
The Part 1 safety follow-up completion visit (Visit 9) should be done approximately 6 weeks after 
last IMP dose; this visit also applies to early withdrawal or permanent treatment discontinuation, 
if applicable. 
The following assessments will be performed as listed in the study flow chart, Section 1.3.1, 
which should be done in the following order: 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• Physical examination 
• General neurological examination 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation  
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Retrieve patient diary 

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10.1.2 Part 2: Treatment phase 
In Part 2, the GZ/SAR402671 dose will be the highest dose determined to be safe and well 
tolerated in Part 1. If patients from Part 1 continue to meet eligibility requirements, they may 
enroll in Part 2, but rerandomization will be required. All assessment at baseline will need to be 
repeated, except for the genetic screening, MRI, LP, and DAT scan, to confirm eligibility of 
patients from Part 1 to enroll in Part 2 (see study flowchart, Section 1.3.2). 
Visit window: The randomization visit (Day 1) can be performed within 60 days from the 
screening visit. For Week 2 through Week 39 visits, a time frame of ±3 days is acceptable using 
Day 1 as reference. For Week 52, a visit window of ±14 days is acceptable using Day 1 as a 
reference. After Week 52 and throughout Period 3, a visit window of ±7 days for all visits is 
acceptable using Day 1 as reference. For Week 216, a visit window of ±14 days is acceptable 
using Day 1 as a reference. (If one visit date is skipped/missed/changed, the next visit should take 
place according to the original schedule). 
Covid-19 outbreak 
Due to Covid-19 outbreak, on-site visits may be delayed with visit window extended up to 
3 months. In this case, IMP can be dispensed to the patient (via direct-to-patient) for a maximum 
duration of 6 months without on-site visit, but with a follow-up by phone (see Section 10.1.2.12). 
If Week 52 visit is delayed, the blinded treatment will be continued until Week 52 visit is 
performed and eligibility assessed for LTFU period.  
Prior to dispensing the IMP, the Investigator will contact (phone, on-line) the patient to review 
AE/SAE/concomitant medication to ensure that no safety issues contraindicate the prolongation of 
the IMP. During the time of IMP prolongation, the Investigator will make every effort to contact 
the patient every 2 weeks to assess the safety. All examinations required for safety that can’t be 
done at the site can be performed locally at a minimum laboratory assessment. 
The on-site visit should be scheduled as close as possible to the theoretical visit date, particularly 
Week 52 which is mandatory.  
In case a patient is infected by the Covid-19 virus and that his/her condition requires a treatment 
that is forbidden by the protocol, the study IMP should be temporarily discontinued. The IMP can 
be resumed once the patient’s health status allows it and if the temporary discontinuation did not 
exceed 4 weeks. For patients who have not completed Week 52 visit, the patient should resume 
IMP for at least 4 weeks prior to Week 52 assessments.  
For other patients infected by Covid-19 requiring concomitant medications not forbidden by the 
protocol, depending on the severity the investigator can decide to interrupt IMP after discussion 
with the Sponsor. 
All the deviations due to the Covid-19 outbreak will be documented in the patient’s file. 
Note: In case the Week 52 visit is delayed and overlaps with the Week 65 visit (for Japanese 
patients only), perform the Week 52 assessments and record the Week 65 visit as a missed visit. If 

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Week 39 is delayed and overlaps with Week 52, perform the Week 52 assessments and record the 
Week 39 visit as a missed visit. 
10.1.2.1 Visit 1: Screening from Day -60 to -1 (Period 1) 
The following activities will be performed: 
• An explanation of the purpose, procedures, potential risks and benefits of this study will be 
provided to the patient. 
• Informed consent signature and date will be collected. 
• In addition to recording any safety issue, the patient diary will also be used to record any 
missing doses after randomization. The patient should bring their diary and any remaining 
capsules to each clinic visit. The site staff will review the patient diary during each clinic 
visit and record excursions from treatment into the eCRF. The patient diary will be 
retrieved when the patient finishes their participation in the study. 
• One blood sample will be collected for investigation of GBA mutations required to include 
patients in the study (see Section 9.6). See Section 17 (Appendix A) for a list of GBA 
mutations. This gene will be sequenced even if historical results are available. Also, this 
sample will be investigated for a specific mutation in the LRRK2 gene (G2019S) and 
patients carrying this mutation will be excluded. Of note, if patient meets these 
two criteria, then the screening visit may proceed for all other items described below. 
• Patient demography will be recorded. 
• BDI-II (Appendix L): At screening, patients with BDI-II of 20-28, inclusive, should be 
evaluated by a mental health specialist before the Investigator can determine if the patient 
would be able to fully participate in the trial. Patients with a BDI-II of >28 (severe 
depression) at screening will be excluded. 
• Confirmation of eligibility by the Investigator 
• GBA complete gene sequencing and LRRK2 G2019S genotyping  
• Medical/surgical history and PD history 
• Confirmation of diagnosis of RBD (historically documented polysomnography or RBD 
screening questionnaire) 
• Review of prior medications 
• Physical examination 
• General neurological examination 
• Record of height and body weight measurements 
• Vital signs (orthostatic): systolic and diastolic blood pressure (mm Hg), heart rate (bpm), 
respiratory rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Laboratory assessments (to be performed by the central laboratory): 

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- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Serum β-HCG pregnancy test (for WOCBP) 
• Full ophthalmology examination and photography 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• GCase activity: dried blood spot from whole blood sample for genetic testing 
• MDS-UPDRS (Appendix F) 
• Hoehn and Yahr (Appendix F); for patients on a stable dose of PD medication, this should 
be done in the “ON” state. 
• PD-CRS (Appendix G)   
• MoCA (Appendix I) 
If patients demonstrate eligibility based on all previous screening criteria:  
• MRI (without contrast) scan will be performed (at least 7 days prior to the end of the 
screening period [Day -8]). 
• LP for collection of CSF will be performed (within 14 days prior to randomization or at 
Day 1, pre-dose).  
• DAT scan will be performed (within 7 days prior to randomization or at Day, 1 pre-dose). 
10.1.2.2 Visit 2: Randomization/baseline at Week 0/Day 1 
Baseline assessments will be completed within the 60-day screening period. Eligibility will be 
reconfirmed prior to randomization/first dose administration on Day 1.  
Patients will receive either placebo or GZ/SAR402671, orally, at the clinic.  
The baseline visit (Day 1) will include assessments and activities as listed in the study flow chart, 
Section 1.3.2, which must be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P)   

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- 
HRPQ (Appendix R) 
- 
CGI (Appendix M) 
- 
FES (Appendix Q) 
• Reconfirmation of eligibility by the Investigator 
• Review of concomitant medications 
• Randomization via IVRS 
• MDS-UPDRS, including H&Y (Appendix F)   
• PD-CRS (Appendix G) 
• Other questionnaires and scales:  
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Physical examination 
• General neurological examination 
• Archival blood sample collected prior to the start of IMP 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analysis 
• Blood sampling for PK analysis at multiple time points: at pre-dose and at 1, 2, 4, and 
8 hours after IMP intake 
• Pharmacogenetics DNA sample (optional; not applicable in Israel [Appendix T]) 
• DAT scan (only if not performed during the screening period, pre-dose) 
• Lumbar puncture for collection of CSF (if not already done during the screening period) 
for biomarker and PK analyses 

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• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.3 Visit 3: Week 0/Day 2 
The following assessments should be done before dosing: 
• Review of concomitant medications 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for PK analysis (24 hours post-Day 1 dose PK sample or 1 hour before 
dosing) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 

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10.1.2.4 Visit 4: Week 2 (±3 days) 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which should be done in the following order: 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analysis 
• Blood sampling for PK analysis (1 hour before dosing [pre-dose]) PK sample) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.5 Visit 5: Week 4 (±3 days) 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which should be done in the following order: 
• BDI-II (Appendix L) 
• Review of concomitant medications 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation 
• Vital signs (orthostatic): systolic and diastolic blood pressure (mm Hg), heart rate (bpm), 
respiratory rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analyses 

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• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.6 Visit 6: Week 13 (±3 days) 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PGIC (Appendix N)  
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
- 
FES (Appendix Q) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G) 
• Other questionnaires and scales 
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Review of concomitant medications 
• General neurological examination  
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 

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• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analysis 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.7 Visit 7: Week 26 (±3 days) 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PGIC (Appendix N)  
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
- 
FES (Appendix Q) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G) 
• Other questionnaires and scales 
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Review concomitant medications 
• Physical examination 
• General neurological examination 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation 

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• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker and PK analyses as listed in study flow chart Section 1.4.2 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.8 Visit 8: Week 39 (±3 days) 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PGIC (Appendix N)  
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
- 
FES (Appendix Q) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G) 
• Other questionnaires and scales 
- 
MoCA (Appendix I) 

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- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Review of concomitant medications 
• General neurological examination 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analysis 
• Dispense IMP 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.9 Visit 9: Week 52 (±14 days) 
Visit 9 will be the last study visit of the blinded treatment period in Part 2. 
Before dosing, the following assessments will be performed as listed in the study flow chart, 
Section 1.3.2, which must be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PGIC (Appendix N)  
- 
CGI (Appendix M) 
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 

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- 
HRPQ (Appendix R) 
- 
FES (Appendix Q) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G) 
• Other questionnaires and scales 
- 
MoCA (Appendix I) 
- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Review concomitant medications 
• Physical examination 
• General neurological examination 
• Record of body weight measurement 
• Vital signs (orthostatic): systolic and diastolic blood pressure (mm Hg), heart rate (bpm), 
respiratory rate (breaths/minute), and temperature (°C) 
• 12-lead ECG 
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Blood sampling for biomarker analyses, GCase activity and PK (as listed in study flow 
chart Section 1.4.2)  
• Pharmacogenetics DNA sample (optional; not applicable in Israel [Appendix T]) 
• Evaluate patients for eligibility (inclusion/exclusion criteria as listed in Section 7.1, 
Section 7.2, and Section 10.1.2.10) to transition to LTFU and receive GZ/SAR402671 
treatment 
• Full ophthalmology examination and photography (must be performed after the 
neurological examination) 
• DAT scan  

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• Lumbar puncture for collection of CSF for PK (as listed in study flow chart Section 1.4.2) 
and biomarker analyses 
• Dispense IMP (the results for all Week 52 assessments, required to check 
inclusion/exclusion criteria, must be received and reviewed before the Week 52 visit is 
registered in IVRS for Week 52 IMP dispensation) 
Remind patient to return to the clinic for next visit, bring their diary and any remaining capsules, 
if patient is enrolled in the LTFU period. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 
10.1.2.10 
Long term follow-up period (Period 3) 
Patients who complete the 52 weeks of double-blinded treatment and who continue to meet 
inclusion criteria I 06, I 07, I 08, and I 09 and none of the exclusion criteria (exclusion criteria E 
02, E 03, E 05, and E 06 will not need to be rechecked) will be eligible to enroll to the LTFU 
period (Period 3) where they will continue to receive appropriate monitoring and will receive 
GZ/SAR402671 treatment after Visit 9. It is important to note that patients will not be informed of 
when the switch will occur, nor will the person(s) performing any of the evaluations.  
Throughout Period 3, a visit window of ±7 days for all visits is acceptable using Day 1 as 
reference.  
During this period, a clinic visit will be scheduled at 6-month intervals (Weeks 78, 104, 130, 156, 
182, and 208) and patients will receive GZ/SAR402671, orally, at the clinic. For Japanese patients 
only, additional clinic visit will be scheduled at Weeks 65, 91, 117, 143, 169, and 195 (Visits 9.1, 
10.1, 11.1, 12.1, 13.1, and 14.1) in addition to the above 6-month interval visits. 
Before dosing, the following assessments will be performed at each study visit (every 6 months), 
as listed in the study flow chart, Section 1.3.3, which should be done in the following order: 
• Whenever possible, the following scales and questionnaires should be done prior to 
clinical interaction with the Investigator: 
- 
BDI-II (Appendix L) 
- 
PDQ-39 (Appendix O) 
- 
EQ-5D (Appendix P) 
- 
HRPQ (Appendix R) 
- 
FES (Appendix Q) 
• MDS-UPDRS, including H&Y (Appendix F) 
• PD-CRS (Appendix G) 
• Other questionnaires and scales 
- 
MoCA (Appendix I) 

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- 
Oral SDMT (Appendix J) 
- 
TMT-A; TMT-B (Appendix K) 
• Review of concomitant medications (every 3 months [13 weeks] for Japanese patients 
only) 
• General neurological examination 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation at 
Visits 10, 12, and 14; at Visits 11, 13, and 15, patients will have a full ophthalmology 
examination and photography (must be performed after the neurological examination) 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) (every 3 months [13 weeks] for Japanese 
patients only) 
• Urine pregnancy test (for WOCBP) 
• Review of current medical conditions, with AE/SAE reporting (if any) (every 3 months 
[13 weeks] for Japanese patients only) 
• Dispense IMP 
At Visit 11/Week 104, Visit 13/Week 156, and Visit 15/Week 208 (ie, yearly), the following 
additional assessments will be performed, as listed in the study flow chart, Section 1.3.3: 
• Blood sampling for biomarker analysis 
• Physical examination and record of body weight measurement 
• 12-lead ECG  
• Laboratory assessments (to be performed by the central laboratory): 
- 
Hematology: CBC, with differential and platelet count; coagulation profile: PT, PTT, 
and INR 
- 
Biochemistry: Sodium, potassium, chloride, calcium, ALT, AST, GGT, ALP, total and 
conjugated bilirubin, urea, serum creatinine, glucose, albumin, total proteins 
• Urinalysis (dipstick) including glucose, protein, bilirubin, urobilinogen, pH, specific 
gravity, blood, ketones, nitrite, and leucocytes. Central urinalysis will be performed if any 
abnormality is observed in the urinalysis dipstick test. 
• DAT scan 
• Dispense IMP (except Visit 15/Week 208) 
• Retrieve patient diary (at Visit 15/Week 208, only for patients who will transition to a 
long-term study with GZ/SAR402671). 
Remind patient to return to the clinic for next visit. 
Remind patient to not take the dose at home on the clinic visiting day, the IMP will be taken at 
clinic. 

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At Visit 15 (Week 208), patients will receive their last dose of GZ/SAR402671 at the clinic.  
Visit 15 (Week 208) will be the last study visit for patients who will transition to a long-term 
study with GZ/SAR402671. 
10.1.2.11 
Eight-week follow-up visit (Period 4, end-of-study visit, Visit 16: Week 216 
±14 days) 
This will be the last study visit. Patients who prematurely and permanently discontinue study 
medication should complete an end of treatment assessment visit (similar to Week 52/end of 
treatment visit for Period 2, Part 2) followed by a 8-week post-treatment follow-up visit 
(Visit 16). The following assessments will be performed as listed in the study flow chart, 
Section 1.3.3, which should be done in the following order: 
• BDI-II (Appendix L) 
• MDS-UPDRS, including H&Y (Appendix F) 
• Review of concomitant medications 
• Physical examination 
• General neurological examination 
• Visual acuity check, slit lamp examination, and fundoscopy without pupil dilation 
• Vital signs: systolic and diastolic blood pressure (mm Hg), heart rate (bpm), respiratory 
rate (breaths/minute), and temperature (°C) 
• Review of current medical conditions, with AE/SAE reporting (if any) 
• Retrieve patient diary.  
10.1.2.12 
Contact for IMP dispensing during Covid-19 outbreak 
In case of delayed visit, the IMP can be dispensed to a patient without on-site visit (see  
Section 10.1.2). Prior to dispensing the IMP, the Investigator will have to contact the patient to 
perform the following: 
• Review of current medical conditions, with AE/SAE reporting (if any) including potential 
signs of depressed mood and changes in vision 
• Review of concomitant medications 
• IMP compliance 
• Assess the patient’s status for prolongation of IMP 
• Dispense IMP 
During the IMP prolongation, the Investigator will make every effort to contact the patient every 
2 weeks to perform the following: 
• Review of current medical conditions, with AE/SAE reporting (if any) including potential 
signs of depressed mood and changes in vision 

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• Review of concomitant medications 
• IMP compliance 
• Assess for patient’s status for prolongation of IMP 
10.2 
DEFINITION OF SOURCE DATA 
Source data are defined as original documents, data, and records. This includes, but is not limited 
to the following: hospital records, clinic and office charts, study-specific source document 
worksheets including MDS-UPDRS worksheets, phone logs, memoranda, evaluation checklists, 
laboratory requisitions, and reports, DAT scan reports and images, ECG tracings, and reports, 
local laboratory reports (if applicable), medication dispensing records, patient questionnaires, 
computer printouts, electronic data/information sources including IVRS/IWRS notifications, and 
any other documentation regarding the patient. 
10.3 
HANDLING OF PATIENT TEMPORARY OR PERMANENT TREATMENT 
DISCONTINUATION AND OF PATIENT STUDY DISCONTINUATION  
The IMP should be continued whenever possible. In case the IMP is stopped, it should be 
determined whether the stop can be made temporarily; permanent IMP discontinuation should be 
a last resort. Any IMP discontinuation should be fully documented in the eCRF. In any case, the 
patient should remain in the study as long as possible. 
Pregnancy will lead to definitive treatment discontinuation in all cases. 
10.3.1 Temporary treatment discontinuation with investigational medicinal products 
Temporary treatment discontinuation because of suspected AEs may be considered by the 
Investigator. After close and appropriate clinical and/or laboratory monitoring, once the 
Investigator considers, according to his/her best medical judgment that the occurrence of the 
concerned event was unlikely due to the IMP, the safety of the patient is not affected, and if the 
selection criteria for the study are still met (refer to Section 7.1 and Section 7.2), treatment with 
the IMP may be re-initiated. For all temporary treatment discontinuations, duration should be 
recorded by the Investigator in the appropriate pages of the eCRF.  
10.3.2 Permanent treatment discontinuation with investigational medicinal product 
Permanent treatment discontinuation is any treatment discontinuation associated with the 
definitive decision from the Investigator or the patient not to re-expose the patient to the IMP at 
any time. 
10.3.3 List of criteria for permanent treatment discontinuation 
The patients may withdraw from treatment with the IMP if they decide to do so, at any time and 
irrespective of the reason, or this may be the Investigator’s decision. All efforts should be made to 
document the reason(s) for treatment discontinuation and this should be documented in the eCRF. 
The patients who develop Grade 3 cataract or higher will be discontinued from study treatment.   

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The following may be justifiable reasons for the Investigator or Sponsor to discontinue a patient 
from treatment. 
Patient specific: 
• The patient experiences two similar SAE or one life-threatening SAE (assessed as related 
by the Investigator and/or the Sponsor) 
• The patient meets criteria for Hy's law (confirmed ALT >5 x ULN range or confirmed 
ALT >3 x ULN and bilirubin >2 x ULN) 
• The patient becomes pregnant 
• The patient develops Grade 3 cataract or higher. 
Trial specific: 
• Any AEs, per Investigator judgment, that may jeopardize the patient's safety 
• Any unblinding of the study treatment by the Investigator 
• Any use of prohibited concomitant treatment (see Section 8.8) 
• At patient’s request, ie, withdrawal of the consent for treatment 
After the company representatives have been made aware of the SAE(s), relevant 
safety/laboratory data will be submitted to the DMC within 72 hours by Global 
Pharmacovigilance and Epidemiology, Clinical and other related departments as designated by the 
Company. 
Any abnormal laboratory value or imaging reports will be immediately rechecked by the Sponsor 
and the central reader, respectively, for confirmation before making a decision of permanent 
discontinuation of the IMP for the concerned patient.  
The DMC will also review data if applicable to assist in determining if AEs should preclude 
continued treatment with GZ/SAR402671.  
If a patient decides to discontinue participation in the study, he/she should be contacted by the 
Study Investigator in order to obtain information about the reason(s) for discontinuation and 
collection of any potential AEs. 
If possible, and after the permanent discontinuation of treatment, the patients will be assessed 
using the procedure normally planned for the Visit 9 (Part 1 Completion Visit) if in Part 1, 
Week 52/end of treatment visit if in Part 2 Period 2, or Week 216 if in Part 2 Period 3.  
All cases of permanent treatment discontinuation should be recorded by the Investigator in the 
appropriate pages of the eCRF when considered as confirmed.   

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10.3.4 Handling of patients after permanent treatment discontinuation 
Patients will be followed-up according to the study procedures specified in this protocol up to the 
scheduled date of study completion, or up to recovery or stabilization of any AE to be 
followed-up as specified in this protocol, whichever comes last.  
All cases of permanent treatment discontinuation should be recorded by the Investigator in the 
appropriate pages of the eCRF when considered as confirmed. 
All patients who prematurely and permanently discontinue study medication prior to Week 8 
(Visit 8) in Part 1, or Week 52 (Visit 9) in Period 2 or Week 208 (Visit 15) in Period 3 of Part 2 
will be asked to continue study visits for safety and efficacy assessments up to and including the 
last scheduled visit, if possible. If the patient refuses, at a minimum, they should be followed up 
for at least 8 weeks after their last scheduled received dose. Patients who prematurely and 
permanently discontinue study medication should complete an end of treatment assessment visit 
(similar to Visit 9 [Part 1 Completion Visit] if in Part 1, Week 52/end of treatment visit if in Part 2 
Period 2, or Week 216 if in Part 2 Period 3) followed by a 8-week post-treatment follow-up visit 
(similar to Visit 9 in Part 1 or Visit 16 in Part 2 [for either Period 2 or 3]).  
Patients who withdraw from the study due to pregnancy should be followed throughout the 
pregnancy up to approximately 6 to 8 weeks beyond the estimated delivery date so that the 
outcome of the pregnancy is determined. Additional follow-up information may be requested 
about the baby until at least one year after the birth of the baby, due to potential risk of 
abnormalities not present at birth. See Section 17, Appendix C for guidance.   
10.3.5  Procedure and consequence for patient withdrawal from study 
The patients may withdraw from the study before study completion if they decide to do so, at any 
time and irrespective of the reason. Withdrawal of consent for treatment should be distinguished 
from withdrawal of consent for follow-up visits and from withdrawal of consent for nonpatient 
contact follow-up, eg, medical records check. Patients requesting withdrawal should be informed 
that withdrawal of consent for follow-up may jeopardize the public health value of the study. 
If possible, the patients are assessed using the procedure normally planned for Visit 9 in Part 1 or 
Week 52 in Part 2 Period 2, or Week 216 if in Part 2 Period 3. If the following examinations 
including lumbar puncture, DAT scan, and PK analyses on plasma and CSF have been performed 
recently, then the Investigator can discuss with Sponsor the need to repeat these examinations. 
Repeat examination(s) will be done on a patient by patient basis. 
Patients who withdraw should be explicitly asked about the contribution of possible AEs to their 
decision to withdraw consent, and any AE information elicited should be documented. Preferably 
the patient should withdraw consent in writing and, if the patient or the patient’s representative 
refuses or is physically unavailable, the site should document and sign the reason for the patient’s 
failure to withdraw consent in writing.  
All study withdrawals should be recorded by the Investigator in the appropriate screens of the 
eCRF and in the patient’s medical records when considered as confirmed. In the medical record, 
at least the date of the withdrawal and the reason should be documented. 

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For patients who fail to return to the site, unless the patient withdraws consent for follow-up, the 
Investigator should make the best effort to recontact the patient (eg, contact patient’s family or 
private physician, review available registries or health care databases), and to determine his/her 
health status, including at least his/her vital status. Attempts to contact such patients must be 
documented in the patient’s records (eg, times and dates of attempted telephone contact, receipt 
for sending a registered letter). 
All data collected up to the patient’s withdrawal will be included in the analyses. The statistical 
analysis plan (SAP) will specify how early withdrawals from treatment will be accounted for in 
the analyses of efficacy endpoints. 
Patients who have withdrawn from the study cannot be rerandomized (treated) in the study, nor, if 
applicable, can they enter the LTFU (Period 3). Their subject and treatment number must not be 
reused. 
10.4 
OBLIGATION OF THE INVESTIGATOR REGARDING SAFETY REPORTING 
10.4.1 Definitions of adverse events  
10.4.1.1 Adverse event 
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. 
10.4.1.2 Serious adverse event 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death, or 
• Is life-threatening, or 
Note: The term “life-threatening” in the definition of “serious” refers to an event in which 
the patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, or 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect 
• Is a medically important event 
Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations, such as important medical events that may not 
be immediately life-threatening or result in death or hospitalization but may jeopardize the 
patient or may require medical or surgical intervention (ie, specific measures or corrective 
treatment) to prevent one of the other outcomes listed in the definition above. 

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Note: The following list of medically important events is intended to serve as a guideline for 
determining which condition has to be considered a medically important event. The list is not 
intended to be exhaustive: 
• Intensive treatment in an emergency room or at home for: 
- 
Allergic bronchospasm  
- 
Blood dyscrasias (ie, agranulocytosis, aplastic anemia, bone marrow aplasia, 
myelodysplasia, pancytopenia, etc),  
- 
Convulsions (seizures, epilepsy, epileptic fit, absence, etc) 
• Development of drug dependence or drug abuse 
• ALT >3 x ULN + total bilirubin >2 x ULN or asymptomatic ALT increase >10 x ULN 
• Suicide attempt or any event suggestive of suicidality 
• Syncope, loss of consciousness (except if documented as a consequence of blood 
sampling) 
• Bullous cutaneous eruptions 
• Cancers diagnosed during the study or aggravated during the study 
• Chronic neurodegenerative diseases (newly diagnosed) or aggravated during the study 
(only if judged unusual/significant by the Investigators in studies assessing specifically the 
effect of an IMP on these diseases) 
10.4.1.3 Adverse event of special interest 
An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the 
Sponsor’s product or program, for which ongoing monitoring and immediate notification by the 
Investigator to the Sponsor is required. Such events may require further investigation in order to 
characterize and understand them. Adverse event of special interest may be added, modified or 
removed during a study by protocol amendment. 
The definition of AESI for this study are as follows: 
• New or worsening lens opacities and cataracts. 
• Pregnancy: 
- 
Pregnancy occurring in a female patient entered in the clinical trial or in a female 
partner of a male patient entered in the clinical trial will be recorded as an AESI with 
immediate notification in all cases. It will be qualified as an SAE only if it fulfills one 
of the seriousness criteria (see Section 10.4.1.2). 
- 
In the event of pregnancy in a female participant, IMP should be discontinued.  
- 
Follow-up of the pregnancy in a female participant or in a female partner of a male 
participant is mandatory until the outcome has been determined (see Section 17 
[Appendix C]). Additional follow-up information may be requested about the baby 

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until at least one year after the birth of the baby, due to potential risk of abnormalities 
not present at birth.  
• Increase in aminotransferase (ALT) (see the “Increase in ALT” flow diagram in Section 17 
[Appendix S] of the protocol). 
• Symptomatic overdose (serious or nonserious) with IMP: 
- 
An overdose (accidental or intentional) with the IMP is an event suspected by the 
Investigator or spontaneously notified by the patient (not based on systematic pills 
count) and defined as at least twice the intended dose within the intended therapeutic 
interval, adjusted according to the tested drug.  
Of note, asymptomatic overdose has to be reported as a standard AE. 
The circumstances (ie, accidental or intentional) should be clearly specified in the verbatim and 
symptoms, if any, entered on separate AE forms.  
10.4.2 General guidelines for reporting adverse events 
• All AEs, regardless of seriousness or relationship to IMP, spanning from the signature of 
the informed consent form until the end of the study as defined by the protocol for that 
patient, are to be recorded on the corresponding page(s) or screen(s) of the eCRF. 
• Whenever possible, diagnosis or single syndrome should be reported instead of symptoms. 
The Investigator should specify the date of onset, intensity, action taken with respect to 
IMP, corrective treatment/therapy given, additional investigations performed, outcome, 
and his/her opinion as to whether there is a reasonable possibility that the AE was caused 
by the IMP or by the study procedure(s).  
• The Investigator should take appropriate measures to follow all AEs until clinical recovery 
is complete and laboratory results have returned to normal, or until progression has been 
stabilized, or until death, in order to ensure the safety of the patients. This may imply that 
observations will continue beyond the last planned visit per-protocol, and that additional 
investigations may be requested by the monitoring team up to as noticed by the Sponsor.  
• Laboratory, vital signs, or ECG abnormalities are to be recorded as AEs only if:  
- 
Symptomatic and/or  
- 
Requiring either corrective treatment or consultation, and/or  
- 
Leading to IMP discontinuation or modification of dosing, and/or  
- 
Fulfilling a seriousness criterion, and/or  
- 
Defined as an AESI 
Instructions for AE reporting are summarized in Table 5. 
10.4.3 Instructions for reporting serious adverse events 
In the case of occurrence of an SAE, the Investigator or any designees must immediately: 

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• ENTER (within 24 hours) the information related to the SAE in the appropriate screens of 
the eCRF; the system will automatically send a notification to the monitoring team after 
approval of the Investigator within the eCRF or after a standard delay. 
• There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. In such case, care should be taken to ensure that the patient's identity is 
protected and the patient's identifiers in the clinical trial are properly mentioned on any 
copy of a source document provided to the Company. For laboratory results, include the 
laboratory normal ranges. 
• All further data updates should be recorded in the eCRF as appropriate. In addition, every 
effort should be made to further document any SAE that is fatal or life-threatening within 
a week (7 days) of the initial notification. 
• A back-up plan (using a paper Case Report Form process) is available and should be used 
when the eCRF system does not work. 
Any SAE brought to the attention of the Investigator at any time after the end of the study for the 
patient and considered by him/her to be caused by the IMP with a reasonable possibility, should 
be reported to the monitoring team. 
10.4.4 Guidelines for reporting adverse events of special interest  
For AESIs, the Sponsor must be informed immediately (ie, within 24 hours), as per SAE 
notification guidelines described in Section 10.4.3, even if not fulfilling a seriousness criterion, 
using the corresponding pages of the eCRF (to be sent) or screens in the eCRF. 
Instructions for AE reporting are summarized in Table 5. 
10.4.5 Guidelines for management of specific laboratory abnormalities 
Decision trees for the management of certain laboratory abnormalities by Sanofi are provided in 
Section 17 [Appendix S].  
The following laboratory abnormalities should be monitored, documented, and managed 
according to the related flow chart in protocol appendices.  
• Neutropenia 
• Thrombocytopenia 
• ALT increase 
• Acute renal insufficiency 
• Suspicion of rhabdomyolysis 

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Table 5 - Summary of adverse event reporting instructions 
Event 
category 
Reporting 
timeframe 
Specific events in this category 
Case Report Form completion 
AE form 
Safety  
complementary 
form 
Other 
specific 
forms 
AE (non-SAE, 
non-AESI) 
Routine 
Any AE that is not SAE or AESI 
Yes 
No 
No 
SAE (non-AESI 
or AESI) 
Expedited 
(within 24 hours) 
Any AE meeting seriousness criterion per 
Section 10.4.1.2 
Yes 
Yes 
No 
 
 
 
 
 
 
AESI  
Expedited 
(within 24 hours) 
New or worsening lens opacities and 
cataracts 
Yes 
Yes 
No 
 
 
Pregnancy 
Yes 
Yes 
Yesa 
 
 
Symptomatic overdose with IMP 
Yes 
Yes 
Yes 
 
 
ALT increase as defined in the protocol 
Yes 
Yes 
Yes 
Abbreviations: AE: adverse event; ALT: alanine aminotransferase; AESI: adverse event of special interest; SAE: serious adverse events. 
a Pregnancy follow-up form (pharmacovigilance reporting form). 
10.5 
OBLIGATIONS OF THE SPONSOR 
During the course of the study, the Sponsor will report in an expedited manner: 
• All SAEs that are both unexpected and at least reasonably related to the IMP (SUSAR), to 
the regulatory authorities, independent ethics committee (IECs)/institutional review boards 
(IRBs) as appropriate, and to the Investigators.  
• All SAEs that are expected and at least reasonably related to the IMPs to the regulatory 
authorities, according to local regulations. 
Adverse events that are expected will be specified in the reference safety information (IB). 
The Sponsor will report all safety observations made during the conduct of the study in the 
clinical study report. 
10.6 
SAFETY INSTRUCTIONS 
At any time during the study, patients who develop ≥Grade 3 cataracts will be discontinued from 
treatment. 
In Part 1, the dose escalation study, if an SAE or ≥Grade 3 AE (NCI, CTCAE Version 4.03) that 
is considered by the Investigator to be related to GZ/SAR402671 and not to underlying disease or 
concomitant medication is observed, the case will be communicated to the DMC and a decision 
should be reached regarding escalation to the next dose with GZ/SAR402671. If 2 patients 
receiving GZ/SAR402671 within the same cohort develop the same SAE or AE (≥Grade 3), 

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dosing within the cohort will be stopped. After stopping, the DMC will review the data and 
provide recommendations on how to proceed. 
In Part 2, if an SAE or ≥Grade 3 AE (NCI, CTCAE v4.03) that is considered by the Investigator 
to be related to GZ/SAR402671 and not to underlying disease or concomitant medication, the 
dose may be temporarily discontinued.  
Other theoretical potential risks considered for general development of any SRT therapy are 
included in the following subsections.  
10.6.1 Liver function tests 
Elevated liver function tests were observed during a 4-week toxicology study in rats.  
In order to closely monitor the liver function, assessment of total protein, albumin, total bilirubin, 
AST, ALT, and ALP are measured as part of the clinical laboratory testing. Patients with a 
positive medical history of hepatitis B or hepatitis C antibody at the screening visit will be 
excluded from the study. 
Guidance for the investigation of elevated liver function tests is provided in Section 17 
(Appendix S). 
10.6.2 Acute renal failure 
See Section 17 (Appendix S). GZ/SAR402671 is not known to be associated with any renal effect; 
this algorithm is provided for informational purposes regarding the assessment of acute renal 
failure. 
10.7 
ADVERSE EVENTS MONITORING 
All events will be managed and reported in compliance with all applicable regulations, and 
included in the final clinical study report. 

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11 
STATISTICAL CONSIDERATIONS 
An SAP will be written and finalized prior to database lock to give guidance to the statistical 
analysis. It will be in compliance with the International Council for Harmonisation (ICH) and the 
FDA’s Guidance for Industry: Statistical Principles for Clinical Trials. 
The Sponsor or its designee will perform the statistical analysis of the data from this study. The 
analysis will be performed using the SAS® statistical software system Version 9.1 or higher. 
11.1 
DETERMINATION OF SAMPLE SIZE 
Part 1: Dose Escalation Phase 
As Part 1 is an exploratory, dose-escalation study, the sample size is not based on the statistical 
power calculation. Each cohort (for non-Japanese patients only) will have a 4:1 randomization 
ratio, and the total sample size will be approximately 15 patients (including 12 on 
GZ/SAR402671 and 3 on placebo).  
For Japanese patients only, each cohort will have a 3:1 randomization ratio, and the total sample 
size will be approximately 12 Japanese patients (including 9 on GZ/SAR402671 and 3 on 
placebo). This sample size in Japanese Part 1 is considered based upon empirical and feasibility 
considerations.  
Therefore, the total sample size in Part 1 will be approximately 27 patients. 
Patients who do not complete a minimum number of scheduled doses of study drug in Part 1 and 
withdraw for reasons other than safety may be replaced. 
Part 2: Treatment Phase 
Approximately 216 PD patients carrying a GBA mutation in total will be randomized in a 
1:1 ratio to the GZ/SAR402671 or placebo groups. A sample size of 108 patients for the 
GZ/SAR402671 group and 108 for the placebo group provides at least 80% power to detect a 
4.06 points improvement compared to the placebo mean change in MDS-UPDRS Parts II+III 
score over 52 weeks. This sample size calculation assumes a 2-sided alpha = 0.05, a standard 
deviation for the change from baseline to Week 52 in MDS-UPDRS Part II+III of 10.01 points 
(estimated from the Parkinson's Progression Markers Initiative [PPMI] database), and allows for 
an approximate 10% early terminations/unevaluable patients.  
A previous study showed that a 3.25 points difference on MDS-UPDRS Part III represent the 
minimal clinically important difference (MCID) for detecting an improvement. It was estimated 
from the PPMI database that the standard deviation for change from baseline to Week 52 in MDS-
UPDRS Part III was 8.01 points; therefore, the MCID of 3.25 points would represent an effect 
size of 0.406. Since no study evaluated the MCID for MDS-UPDRS Part II+III, the same effect 
size of 0.406 was assumed, resulting in an estimated MCID of 4.06 points, using the standard 

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deviation of 10.01 for change from baseline to Week 52 in MDS-UPDRS Part II+III also 
estimated from the PPMI database. 
Of note, the approximate 27 (12 Japanese and 15 non-Japanese) early-stage PD patients carrying a 
GBA mutation from Part 1 may be re-randomized and participate in all of the assessments in 
Part 2 of this study; however, they will not contribute to the primary efficacy, safety, PK and 
pharmacodynamics analyses, and will be described separately. 
Calculations were made using nQuery 7.0 Advisor software. 
11.2 
DISPOSITION OF PATIENTS 
Screened patients are defined as any patient who signed the informed consent.  
Randomized patients consist of all screened patients, with a double-blind treatment kit number 
allocated and recorded in the IVRS/IWRS database, regardless of whether the treatment kit was 
used or not. Patients treated without being randomized or treated with a double-blind treatment kit 
before the randomization will not be considered as randomized and will not be included in any 
analysis population. The safety experience of patients treated and not randomized will be reported 
separately, and these patients will not be included in the safety population. 
For any patient randomized more than once in Part 2 of the study, only the data associated with 
the first randomization will be used in any analysis population. The safety experience associated 
with any later randomization will be assessed separately. 
11.3 
ANALYSIS POPULATIONS 
11.3.1 Efficacy populations 
11.3.1.1 Intent–to-treat population 
The Part 2 intent-to-treat (ITT) population will be defined as all randomized patients in Part 2. 
Patients from Part 1 who are rerandomized in Part 2 will not be included in Part 2 ITT population. 
The Part 2 ITT population is the primary analysis population for all efficacy endpoints. Patients 
will be analyzed in the treatment group to which they were randomized. 
In addition, exploratory efficacy endpoints in Part 1 of the study will be described separately for 
non-Japanese and Japanese patients: 
• The Part 1 non-Japanese ITT population will be defined as all non-Japanese randomized 
patients in Part 1. Patients will be analyzed in the treatment group to which they were 
randomized. 
• The Part 1 Japanese ITT population will be defined as all Japanese randomized patients in 
Part 1. Patients will be analyzed in the treatment group to which they were randomized. 

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11.3.1.2 Per-protocol population 
The Part 2 PP population will be defined as a subset of the Part 2 ITT population that excludes 
patients with major protocol deviations that potentially impact the primary efficacy endpoint. The 
criteria for exclusion of patients from the Part 2 PP population will be determined and 
documented prior to database lock. The Part 2 PP population will be used for sensitivity analysis 
purposes. 
11.3.2 Safety population 
The safety populations considered for safety analyses will be the randomized population who did 
actually receive at least one dose or part of a dose of the double-blind IMP. Patients will be 
analyzed according to the treatment actually received (GZ/SAR402671 or placebo). 
Safety populations will be defined separately for Part 1 and Part 2 of the study: 
• The Part 1 non-Japanese safety population will be defined as all non-Japanese randomized 
patients in non-Japanese Part 1 who received at least 1 dose of study medication in Part 1 
of the study. All safety analyses in Part 1 of the study will be performed on the Part 1 
non-Japanese safety population.  
• The Part 1 Japanese safety population will be defined as all Japanese randomized patients 
in Part 1 who received at least 1 dose of study medication in Part 1 of the study. All safety 
analyses in Japanese Part 1 of the study will be performed on the Part 1 Japanese safety 
population. 
• The Part 2 safety population will be defined as all randomized patients in Part 2 who 
received at least 1 dose of study medication in Part 2 of the study. Patients from Part 1 
who are re-randomized in Part 2 will not be included in Part 2 safety population, and will 
be described separately. All safety analyses in Part 2 of the study will be performed on the 
Part 2 safety population. 
In addition:  
• Nonrandomized but treated patients will not be part of the safety populations, but their 
safety data will be presented separately.  
• Randomized patients for whom it is unclear whether they took the study medication will 
be included in the safety population as randomized. 
• For patients receiving more than one study treatment within the same part of the study, the 
treatment group allocation for as-treated analysis will be the one to which the patient was 
treated with the longest duration. 
11.3.3 Pharmacokinetics/pharmacodynamics population 
The PK and pharmacodynamics populations will be defined as all patients who received at least 
1 dose of GZ/SAR402671 and who have at least one PK or pharmacodynamics assessment, 
respectively. 

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Pharmacokinetics and pharmacodynamics data will be described separately for Part 1 and Part 2 
of the study, and separately for non-Japanese and Japanese patients: 
• The Part 1 non-Japanese pharmacodynamics and PK populations will be defined as all 
non-Japanese patients in Part 1 who received at least 1 dose of GZ/SAR402671 and who 
have at least one pharmacodynamics or PK assessment, respectively. 
• The Part 1 Japanese pharmacodynamics and PK populations will be defined as all 
Japanese patients in Part 1 who received at least 1 dose of GZ/SAR402671 and who have 
at least one pharmacodynamics or PK assessment, respectively. 
• The Part 2 non-Japanese pharmacodynamics and PK populations will be defined as all 
patients in Part 2 who received at least 1 dose of GZ/SAR402671 and who have at least 
one pharmacodynamics or PK assessment, respectively. Patients from Part 1 who are 
rerandomized in Part 2 will not be included in Part 2 pharmacodynamics and PK 
populations, and will be described separately. 
• The Part 2 Japanese pharmacodynamics and PK populations will be defined as all 
Japanese patients in Part 2 who received at least 1 dose of GZ/SAR402671 and who have 
at least one pharmacodynamics or PK assessment, respectively. Patients from Part 1 who 
are rerandomized in Part 2 will not be included in Part 2 Japanese pharmacodynamics and 
PK populations, and will be described separately. 
11.4 
STATISTICAL METHODS 
11.4.1 Extent of study treatment exposure and compliance 
The extent of study treatment exposure and compliance will be assessed separately for Part 1 and 
Part 2 of the study, and summarized by actual treatment received within the Part 1 safety 
population and Part 2 safety population respectively. 
Within each part of the study, duration of IMP exposure is defined as: last dose date - first dose 
date +1 day, regardless of unplanned intermittent discontinuations. 
11.4.2 Analyses of efficacy endpoints 
All analyses of efficacy endpoints will be done on Part 2 of the study and will not include patients 
from Part 1 who are rerandomized in Part 2. Efficacy data in patients from Part 1 will be 
described separately, with no formal statistical testing. 
11.4.2.1 Analysis of primary efficacy endpoint 
The primary efficacy endpoint is the change from baseline to Week 52 in MDS-UPDRS 
Part II+III score. 
The primary analysis will be based on an ITT approach, including all data regardless of adherence 
to treatment and protocol. Change from baseline in MDS-UPDRS Part II+III score will be 
analyzed using a mixed effect model with repeated measures (MMRM). All postbaseline data 

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available within Week 13 to Week 52 analysis windows will be used and missing data will be 
accounted for by the MMRM model. The model will include the fixed categorical effects of 
treatment group (GZ/SAR402671 versus placebo), randomization strata, time point (Week 13, 
Week 26, Week 39, and Week 52), treatment-by-time point interaction as well as the continuous 
fixed covariates of baseline MDS-UPDRS Part II+III score. This model will provide baseline 
adjusted least squares means estimates at Week 52 for both treatment groups with their 
corresponding standard errors and 95% confidence intervals (CI). To compare the 
GZ/SAR402671 group to the placebo group, an appropriate contrast statement will be used to test 
the differences of these estimates, at the 2-sided 0.05 level. 
The MMRM model relies on the “missing-at-random” (MAR) assumption. As the possibility for a 
not-missing-at-random (NMAR) missingness mechanism cannot be excluded, a sensitivity 
analysis to explore the impact of nonignorable missingness on the primary efficacy analysis will 
be conducted. 
The sensitivity analysis will use a control-based pattern-mixture model (PMM) method. This 
PMM method will make the assumption that, in case of missing data after permanent treatment 
discontinuation, the MDS-UPDRS Part II+III scores for patients in the GZ/SAR402671 arm will 
follow the same trajectory as for patients in the placebo arm. As a consequence, missing data after 
permanent treatment discontinuation will be imputed using a model estimated solely from data 
observed in the placebo arm. Missing data during the treatment period will be imputed separately 
assuming MAR, using a model estimated from data observed during the treatment period within 
the same treatment arm. Missing values will be imputed 100 times to generate 100 complete data 
sets. Each completed dataset will be analyzed using an analysis of covariance (ANCOVA) of 
change from baseline to Week 52 in MDS-UPDRS Part II+III score, including the fixed 
categorical effects of treatment group (GZ/SAR402671 versus placebo), randomization strata, as 
well as the continuous fixed covariates of baseline value. The final results will be obtained by 
combining the least squares means and least squares mean differences from these 100 analyses, 
using Rubin’s formula. 
The primary analysis will be repeated using a PP approach. Movement Disorder Society-Unified 
Parkinson’s Disease Rating Scale data collected after a major protocol deviation that potentially 
impacts the primary efficacy endpoint will be excluded from this analysis. The criteria for 
exclusion of data will be determined and documented prior to database lock. The PP analysis will 
be used for sensitivity analysis purposes. 
11.4.2.2 Analyses of secondary efficacy endpoints 
Secondary efficacy endpoints include: 
• Change in PD-CRS (total score) from baseline to Week 52.  
• Change in MDS-UPDRS Parts I+II+III from baseline to Week 52. 
• Change in H&Y score from baseline to Week 52. 
Secondary endpoints will be analyzed using the same MMRM model as for the primary efficacy 
endpoint. 

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11.4.2.3 Multiplicity considerations 
In order to handle multiple secondary endpoints, the overall type-I error will be controlled by the 
use of a hierarchical approach. Statistical significance of the primary endpoint at the 2-sided 0.05 
alpha level is required before drawing inferential conclusions about first secondary endpoint (refer 
to order of list in Section 9.2.2). Inferential conclusions about successive secondary endpoints 
require statistical significance of the prior one. 
This fixed hierarchical approach will ensure a strong control of the overall type-I error rate at the 
2-sided 0.05 level. 
No further adjustments will be made for exploratory endpoints for which p-values will be 
provided for descriptive purpose only. 
11.4.3 Analyses of safety data 
Safety data will be described separately for Part 1 and Part 2 of the study, and separately for 
Japanese and non-Japanese patients. 
Safety and tolerability in the Japanese patients from Part 1 will be compared to the non-Japanese 
patients.   
All safety analyses will be performed on the Part 1 safety population and Part 2 safety population 
respectively. The summary of safety results will be presented by treatment group actually 
received. 
The baseline value is defined generally as the last available value before randomization, within 
each part of the study. 
For all safety data, the observation period will be divided into 3 segments within each part of the 
study: 
• The pretreatment period is defined as the time between the date of the informed consent 
and the first administration of double-blind IMP. 
• The on-treatment period is defined as the period from the time of first IMP 
administration up to  6 weeks after the last administration of the IMP. 
• The post-treatment period starts on the day after the end of the on-treatment period. 
The following definitions will be applied to laboratory parameters, vital signs, and ECGs. 
• The potentially clinically significant abnormality (PCSA) values are defined as abnormal 
values considered medically important by the Sponsor according to predefined 
criteria/thresholds based on literature review and defined by the Sponsor for clinical 
laboratory tests, vital signs, and ECGs.  
• The PCSA criteria will determine which patients had at least 1 PCSA during the 
on-treatment period, taking into account all evaluations performed during the on-treatment 
period, including unscheduled or repeated evaluations. The number of all such patients 
will be the numerator for the on-treatment PCSA percentage. 

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11.4.3.1 Adverse events 
Adverse event incidence tables will be presented by system organ class (sorted by internationally 
agreed order), high-level group term, high-level term, and preferred term sorted in alphabetical 
order for each treatment group, the number (n) and percentage (%) of patients experiencing an 
AE. Multiple occurrences of the same event in the same patient will be counted only once in the 
tables within a treatment period. The denominator for computation of percentages is the safety 
population within each treatment group. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities. The 
AEs will be classified into predefined standard categories according to chronological criteria:  
• Pretreatment AEs: AEs that occurred or worsened during the pretreatment period; 
• Treatment-emergent AEs: AEs that occurred or worsened during the on-treatment period; 
• Post-treatment AEs: AEs that occurred or worsened during the post-treatment period. 
11.4.3.2 Laboratory data and vital signs 
The summary statistics (including mean, standard deviation, median, Q1, Q3, minimum, and 
maximum) of all laboratory variables and all vital sign parameters (raw data and changes from 
baseline) will be calculated for each visit, last and worst value assessed during the treatment 
period, and presented by treatment group. For selected parameters, mean changes from baseline 
with the corresponding standard error will be plotted over time (at same time points) in each 
treatment group. 
The incidence of PCSAs at any time during the TEAE period (on-treatment PCSAs) will be 
summarized by treatment group whatever the baseline level and/or according to the following 
baseline categories: 
• Normal/missing. 
• Abnormal according to PCSA criterion or criteria. 
For laboratory parameters for which PCSA criterion is not defined, similar table(s) using the 
normal range could be provided. 
11.4.4 Analyses of pharmacokinetic and pharmacodynamic variables 
Pharmacokinetic and pharmacodynamic data will be described separately for Part 1 and Part 2 of 
the study, and separately for Japanese and non-Japanese patients. 
Pharmacokinetics and pharmacodynamics in the Japanese patients from Part 1 will be compared 
to the non-Japanese patients.   
Pharmacodynamic parameters will be summarized and compared between GZ/SAR402671 and 
placebo administration using descriptive statistics at each time point, including assessment of 
observed values, and percent change from baseline. p-Values for statistical comparisons will be 
provided for descriptive purpose. Plasma PK parameters will be summarized using descriptive 

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statistics and also analyzed using noncompartmental methods. CSF exposure of GZ/SAR402671 
will be summarized using descriptive statistics at each time point. 
Pharmacokinetic parameters may be estimated for metabolites using noncompartmental methods 
and reported for individual patients and summarized using descriptive statistics.  
With respect to biomarkers, levels of plasma, serum or CSF biomarkers, as well as changes from 
baseline, will be summarized descriptively by time point. 
11.5 
INTERIM ANALYSIS 
11.5.1 Interim efficacy analysis  
No interim analysis is planned for this study.  
11.5.2 Two-step final analysis 
The final analysis will be conducted in two steps: 
• First step: analysis of the 52-week treatment period of Part 2 of the study: 
- 
The analysis of the 52-week treatment period of Part 2 of the study will be conducted 
when all patients from Part 2 have been randomized and have all their data up to 
Week 52 collected and validated, and will consist in the final analysis of the primary, 
secondary, and exploratory endpoints up to Week 52. The safety analysis will be 
performed on all safety data collected and validated at the time of the first analysis. 
This analysis will be conducted after a partial database lock and treatment unblinding. 
• Second step: analysis up to Week 208 of Part 2 of the study: 
The second analysis will be conducted at the end of the study and will consist of the final analysis 
up to Week 208. Specific analyses of efficacy and safety data up to Week 208 will be described in 
the SAP. This analysis will be conducted after the final database lock. 

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12 
ETHICAL AND REGULATORY CONSIDERATIONS 
12.1 
ETHICAL AND REGULATORY STANDARDS 
This clinical trial will be conducted by the Sponsor, the Investigator, and delegated Investigator 
staff and Sub-Investigator, in accordance with consensus ethics principles derived from 
international ethics guidelines, including the Declaration of Helsinki, and the ICH guidelines for 
Good Clinical Practice (GCP), all applicable laws, rules, and regulations. 
This clinical trial will be recorded in a free, publicly accessible, internet-based registry, no later 
than 21 days after the first patient enrollment, in compliance with applicable regulatory 
requirements and with Sanofi public disclosure commitments.  
12.2 
INFORMED CONSENT 
The Investigator (according to applicable regulatory requirements), or a person designated by the 
Investigator, and under the Investigator's responsibility, should fully inform the patient of all 
pertinent aspects of the clinical trial including the written information giving approval/favorable 
opinion by the IRB/IEC. All participants should be informed to the fullest extent possible about 
the study, in language and terms they are able to understand. 
Prior to a patient’s participation in the clinical trial, the written informed consent form should be 
signed, name filled in and personally dated by the patient or by the patient’s legally acceptable 
representative, and by the person who conducted the informed consent discussion. A copy of the 
signed and dated written informed consent form will be provided to the patient.  
Prior to collection of blood for pharmacogenetics, the optional pharmacogenetics informed 
consent form (written) should be signed, name filled in, and personally dated by the patient or by 
the patient’s legally acceptable representative, and by the person who conducted the informed 
consent discussion. A copy of the signed and dated written optional informed consent form will be 
provided to the patient. 
All informed consent forms used by the Investigator for obtaining the patient's informed consent 
must be reviewed and approved by the Sponsor prior to submission to the appropriate ethics 
committee (IRB/IEC) for approval/favorable opinion. 
12.3 
HEALTH AUTHORITIES AND INSTITUTIONAL REVIEW BOARD/INDEPENDENT 
ETHICS COMMITTEE (IRB/IEC)  
As required by local regulation, the Investigator or the Sponsor must submit this clinical trial 
protocol to the health authorities (competent regulatory authority) and the appropriate IRB/IEC, 
and is required to forward to the respective other party a copy of the written and dated 
approval/favorable opinion signed by the chairman with IRB/IEC composition. 

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The clinical trial (study number, clinical trial protocol title and version number), the documents 
reviewed (clinical trial protocol, informed consent form, IB with any addenda or labeling 
documents [summary of product characteristics, package insert], Investigator’s curriculum vitae, 
etc) and the date of the review should be clearly stated on the written (IRB/IEC) 
approval/favorable opinion. 
The IMP will not be released at the study site and the Investigator will not start the study before 
the written and dated approval/favorable opinion is received by the Investigator and the Sponsor. 
During the clinical trial, any amendment or modification to the clinical trial protocol should be 
submitted to the health authorities (competent regulatory authority), as required by local 
regulation, in addition to the IRB/IEC before implementation, unless the change is necessary to 
eliminate an immediate hazard to the patients, in which case the health authorities (competent 
regulatory authority) and the IRB/IEC should be informed as soon as possible. They should also 
be informed of any event likely to affect the safety of patients or the continued conduct of the 
clinical trial, in particular any change in safety. All updates to the IB or labeling information will 
be sent to the IRB/IEC and to health authorities (competent regulatory authority), as required by 
local regulation. 
A progress report is sent to the IRB/IEC at least annually and a summary of the study’s outcome 
at the end of the study.  

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13 
STUDY MONITORING 
13.1 
RESPONSIBILITIES OF THE INVESTIGATOR(S) 
The Investigator is required to ensure compliance with all procedures required by the clinical trial 
protocol and with all study procedures provided by the Sponsor (including security rules). The 
Investigator agrees to provide reliable data and all information requested by the clinical trial 
protocol (with the help of the eCRF, Discrepancy Resolution Form or other appropriate 
instrument) in an accurate and legible manner according to the instructions provided and to ensure 
direct access to source documents by Sponsor representatives. 
If any circuit includes transfer of data particular attention should be paid to the confidentiality of 
the patient's data to be transferred. 
The Investigator may appoint such other individuals as he/she may deem appropriate as 
Sub-Investigators to assist in the conduct of the clinical trial in accordance with the clinical trial 
protocol. All Sub-Investigators shall be appointed and listed in a timely manner. The 
Sub-Investigators will be supervised by and work under the responsibility of the Investigator. The 
Investigator will provide them with a copy of the clinical trial protocol and all necessary 
information. 
13.2 
RESPONSIBILITIES OF THE SPONSOR 
The Sponsor of this clinical trial is responsible to regulatory authorities for taking all reasonable 
steps to ensure the proper conduct of the clinical trial with regards to ethics, clinical trial protocol 
compliance, and integrity and validity of the data recorded on the eCRFs. Thus, the main duty of 
the monitoring team is to help the Investigator and the Sponsor maintain a high level of ethical, 
scientific, technical and regulatory quality in all aspects of the clinical trial. 
At regular intervals during the clinical trial, the site will be contacted, through monitoring visits, 
letters or telephone calls, by a representative of the monitoring team to review study progress, 
Investigator and patient compliance with clinical trial protocol requirements and any emergent 
problems. These monitoring visits will include but not be limited to review of the following 
aspects: patient informed consent, patient recruitment and follow-up, SAE documentation and 
reporting, AESI documentation and reporting, AE documentation, IMP allocation, patient 
compliance with the IMP regimen, IMP accountability, concomitant therapy use and quality of 
data. 
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in separate study documents. 

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13.3 
SOURCE DOCUMENT REQUIREMENTS 
According to the ICH GCP, the monitoring team must check the eCRF entries against the source 
documents, except for the pre-identified source data directly recorded in the eCRF. The informed 
consent form will include a statement by which the patient allows the Sponsor’s duly authorized 
personnel, the ethics committee (IRB/IEC), and the regulatory authorities to have direct access to 
original medical records which support the data on the eCRFs (eg, patient’s medical file, 
appointment books, original laboratory records, etc). These personnel, bound by professional 
secrecy, must maintain the confidentiality of all personal identity or personal medical information 
(according to confidentiality and personal data protection rules). 
13.4 
USE AND COMPLETION OF ELECTRONIC CASE REPORT FORMS (eCRFs) AND 
ADDITIONAL REQUEST 
It is the responsibility of the Investigator to maintain adequate and accurate eCRFs (according to 
the technology used) designed by the Sponsor to record (according to Sponsor instructions) all 
observations and other data pertinent to the clinical investigation in a timely manner. All eCRFs 
should be completed in their entirety in a cohesive manner to ensure accurate interpretation of 
data. 
Should a correction be made, the corrected information will be entered in the eCRF overwriting 
the initial information. An audit trail allows identifying the modification.  
Data are available within the system to the Sponsor as soon as they are entered in the eCRF. 
The computerized handling of the data by the Sponsor may generate additional requests 
(Discrepancy Resolution Form) to which the Investigator is obliged to respond by confirming or 
modifying the data questioned. The requests with their responses will be managed through the 
eCRF. 
13.5 
USE OF COMPUTERIZED SYSTEMS 
The complete list of computerized systems used for the study is provided in a separate document 
which is maintained in the Sponsor and Investigator study files. 

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14 
ADDITIONAL REQUIREMENTS 
14.1 
CURRICULUM VITAE 
A current copy of the curriculum vitae describing the experience, qualification, and training of 
each Investigator and Sub-Investigator will be signed, dated, and provided to the Sponsor prior to 
the beginning of the clinical trial. 
14.2 
RECORD RETENTION IN STUDY SITES 
The Investigator must maintain confidential all study documentation, and take measures to 
prevent accidental or premature destruction of these documents. 
The Investigator should retain the study documents at least 15 years after the completion or 
discontinuation of the clinical trial. 
However, applicable regulatory requirements should be taken into account in the event that a 
longer period is required. 
The Investigator must notify the Sponsor prior to destroying any study essential documents 
following the clinical trial completion or discontinuation. 
If the Investigator’s personal situation is such that archiving can no longer be ensured by him/her, 
the Investigator shall inform the Sponsor and the relevant records shall be transferred to a 
mutually agreed upon designee.  
14.3 
CONFIDENTIALITY 
All information disclosed or provided by the Sponsor (or any company/institution acting on their 
behalf), or produced during the clinical trial, including, but not limited to, the clinical trial 
protocol, personal data in relation to the patients, the eCRFs, the IB, and the results obtained 
during the course of the clinical trial, is confidential, prior to the publication of results. The 
Investigator and any person under his/her authority agree to undertake to keep confidential and 
not to disclose the information to any third party without the prior written approval of the 
Sponsor. 
However, the submission of this clinical trial protocol and other necessary documentation to the 
ethics committee (IRB/IEC) is expressly permitted, the IRB/IEC members having the same 
obligation of confidentiality. 
The Sub-Investigators shall be bound by the same obligation as the Investigator. The Investigator 
shall inform the Sub-Investigators of the confidential nature of the clinical trial. 
The Investigator and the Sub-Investigators shall use the information solely for the purposes of the 
clinical trial, to the exclusion of any use for their own or for a third party’s account. 

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14.4 
PROPERTY RIGHTS 
All information, documents and IMP provided by the Sponsor or its designee are and remain the 
sole property of the Sponsor. 
The Investigator shall not and shall cause the delegated Investigator staff /Sub-Investigator not to 
mention any information or the Product in any application for a patent or for any other intellectual 
property rights. 
All the results, data, documents and inventions, which arise directly or indirectly from the clinical 
trial in any form, shall be the immediate and exclusive property of the Sponsor. 
The Sponsor may use or exploit all the results at its own discretion, without any limitation to its 
property right (territory, field, continuance). The Sponsor shall be under no obligation to patent, 
develop, market or otherwise use the results of the clinical trial. 
As the case may be, the Investigator and/or the Sub-Investigators shall provide all assistance 
required by the Sponsor, at the Sponsor’s expense, for obtaining and defending any patent, 
including signature of legal documents. 
14.5 
DATA PROTECTION 
• The patient’s personal data, which are included in the Sponsor database shall be treated in 
compliance with all applicable laws and regulations including GDPR (Global Data 
Protection Regulation) 
• When archiving or processing personal data pertaining to the Investigator and/or to the 
patients, the Sponsor shall take all appropriate measures to safeguard and prevent access to 
this data by any unauthorized third party 
• The Sponsor also collects specific data regarding Investigator as well as personal data 
from any person involved in the study which may be included in the Sponsor’s databases, 
shall be treated by both the Sponsor and the Investigator in compliance with all applicable 
laws and regulations 
Patient race or ethnicity (eg, "American Indian or Alaska Native, Asian, Black/Black or African 
American, Native Hawaiian or Other Pacific Islander, White, Not Reported or Unknown") will be 
collected if permitted by local regulations as these are required by several regulatory authorities 
(eg, on afro American population for FDA, or on Japanese population for the Pharmaceuticals and 
Medical Devices Agency in Japan). 
14.6 
INSURANCE COMPENSATION 
The Sponsor certifies that it has taken out a liability insurance policy covering all clinical trials 
under its sponsorship. This insurance policy is in accordance with local laws and requirements. 
The insurance of the Sponsor does not relieve the Investigator and the collaborators from any 

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obligation to maintain their own liability insurance policy. An insurance certificate will be 
provided to the IECs/IRBs or regulatory authorities in countries requiring this document.  
14.7 
SPONSOR AUDITS AND INSPECTIONS BY REGULATORY AGENCIES 
For the purpose of ensuring compliance with the clinical trial protocol, GCP, and applicable 
regulatory requirements, the Investigator should permit auditing by or on the behalf of the 
Sponsor and inspection by regulatory authorities. 
The Investigator agrees to allow the auditors/inspectors to have direct access to his/her study 
records for review, being understood that these personnel is bound by professional secrecy, and as 
such will not disclose any personal identity or personal medical information. 
The Investigator will make every effort to help with the performance of the audits and inspections, 
giving access to all necessary facilities, data, and documents. 
As soon as the Investigator is notified of a planned inspection by the authorities, he will inform 
the Sponsor and authorize the Sponsor to participate in this inspection. 
The confidentiality of the data verified and the protection of the patients should be respected 
during these inspections. 
Any result and information arising from the inspections by the regulatory authorities will be 
immediately communicated by the Investigator to the Sponsor. 
The Investigator shall take appropriate measures required by the Sponsor to take corrective 
actions for all problems found during the audit or inspections. 
14.8 
PREMATURE DISCONTINUATION OF THE STUDY OR PREMATURE CLOSE-OUT OF 
A SITE 
14.8.1 By the Sponsor  
The Sponsor has the right to terminate the study or the participation of an individual site at any 
time, for any reason, including but not limited to the following:  
• The information on the product leads to doubt as to the benefit/risk ratio 
• Patient enrollment is unsatisfactory 
• The Investigator has received from the Sponsor all IMP, means, and information necessary 
to perform the clinical trial and has not included any patient after a reasonable period of 
time mutually agreed upon 
• Noncompliance of the Investigator or Sub-Investigator, delegated staff with any provision 
of the clinical trial protocol, and breach of the applicable laws and regulations or breach of 
the ICH GCP 
• The total number of patients are included earlier than expected 

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• If the study no longer meets the development needs of the compound or business needs of 
the company 
In any case, the Sponsor will notify the Investigator of its decision by written notice. 
14.8.2 By the Investigator 
The Investigator may terminate his/her participation upon 30 days’ prior written notice if the 
study site or the Investigator for any reason becomes unable to perform or complete the clinical 
trial.  
In the event of premature discontinuation of the study or premature close-out of a site, for any 
reason whatsoever, the appropriate IRB/IEC and regulatory authorities should be informed 
according to applicable regulatory requirements. 
14.9 
CLINICAL TRIAL RESULTS 
The Sponsor will be responsible for preparing a clinical study report and to provide a summary of 
study results to the Investigator. 
14.10 PUBLICATIONS AND COMMUNICATIONS 
The Investigator undertakes not to make any publication or release pertaining to the study and/or 
results of the study prior to the Sponsor’s written consent, being understood that the Sponsor will 
not unreasonably withhold its approval. 
As the study is being conducted at multiple sites, the Sponsor agrees that, consistent with 
scientific standards, a primary presentation or publication of the study results based on global 
study outcomes shall be sought. In addition to the SAC, PIs at the 3 first sites enrolling the most 
patients will also be included as authors for the primary publication. However, if no multicenter 
publication is submitted, underway, or planned within 12 months of the completion of this study 
at all sites, the Investigator shall have the right to publish or present independently the results of 
this study in agreement with other Investigators and stakeholders. The Investigator shall provide 
the Sponsor with a copy of any such presentation or publication for review and comment at least 
30 days in advance of any presentation or submission for publication. In addition, if requested by 
the Sponsor, any presentation or submission for publication shall be delayed for a limited time, 
not to exceed 90 days, to allow for filing of a patent application or such other justified measures 
as the Sponsor deems appropriate to establish and preserve its proprietary rights.  
The Investigator shall not use the name(s) of the Sponsor and/or its employees in advertising or 
promotional material or publication without the prior written consent of the Sponsor. The Sponsor 
shall not use the name(s) of the Investigator and/or the collaborators in advertising or promotional 
material or publication without having received his/her and/or their prior written consent(s). 
The Sponsor has the right at any time to publish the results of the study. 

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15 
CLINICAL TRIAL PROTOCOL AMENDMENTS 
All appendices attached hereto and referred to herein are made part of this clinical trial protocol. 
The Investigator should not implement any deviation from, or changes to the clinical trial protocol 
without agreement by the Sponsor and prior review and documented approval/favorable opinion 
from the IRB/IEC and/or notification/approval of health authorities (competent regulatory 
authority) of an amendment, as required by local regulation, except where necessary to eliminate 
an immediate hazard(s) to clinical trial patients, or when the change(s) involves only logistical or 
administrative aspects of the study. Any change agreed upon will be recorded in writing, the 
written amendment will be signed by the Investigator and by the Sponsor and the signed 
amendment will be filed with this clinical trial protocol. 
Any amendment to the clinical trial protocol requires written approval/favorable opinion by the 
IRB/IEC prior to its implementation, unless there are overriding safety reasons. 
In case of substantial amendment to the clinical trial protocol, approval from the health authorities 
(competent regulatory authority) will be sought before implementation. 
In some instances, an amendment may require a change to the informed consent form. The 
Investigator must receive an IRB/IEC approval/favorable opinion concerning the revised informed 
consent form prior to implementation of the change and patient signature should be recollected if 
necessary. 

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16 
BIBLIOGRAPHIC REFERENCES 
1. Beutler E, Grabowski G. Gaucher disease. In: Scriver C, Beaudet AL, Sly WS, Valle D, 
editors. The metabolic and molecular basis of inherited disease. 8th ed. New York: 
McGraw‑Hill; 2001; p. 3635–68. 
2. Horowitz M, Wilder S, Horowitz Z, Reiner O, Gelbart T, Beutler E. The human 
glucocerebrosidase gene and pseudogene: structure and evolution. Genomics. 1989 
Jan;4(1):87-96. 
3. Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and 
polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008 
May;29(5):567-83. 
4. Lwin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E. Glucocerebrosidase 
mutations in subjects with parkinsonism. Mol Genet Metab. 2004 Jan;81(1):70–3. 
5. Toft M, Pielsticker L, Ross OA, Aasly JO, Farrer MJ. Glucocerebrosidase gene mutations and 
Parkinson disease in the Norwegian population. Neurology. 2006 Feb;66(3):415-7. 
6. Winder-Rhodes SE, Evans JR, Ban M, Mason SL, Williams-Gray CH, Foltynie T, et al. 
Glucocerebrosidase mutations influence the natural history of Parkinson’s disease in a 
community-based incident cohort. Brain. 2013 Feb;136(Pt 2):392-9. 
7. Brockmann K, Srulijes K, Pflederer S, Hauser AK, Schulte C, Maetzler W, et al. GBA-
associated Parkinson's disease: reduced survival and more rapid progression in a prospective 
longitudinal study. Mov Disord. 2015 Mar;30(3):407-11. 
8. Oeda T, Umemura A, Mori Y, Tomita S, Kohsaka M, Park K, et al. Impact of 
glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease. 
Neurobiol Aging. 2015 Dec;36(12):3306-13. 
9. Goker-Alpan O, Giasson BI, Eblan MJ, Nguyen J, Hurtig HI, Lee VM, et al. 
Glucocerebrosidase mutations are an important risk factor for Lewy body disorders. 
Neurology. 2006 Sep;67(5):908-10. 
10. Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, et al. Gaucher disease 
glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. 
Cell. 2011 Jul;146(1):37-52. 
11. Goker-Alpan O, Stubblefield BK, Giasson BI, Sidransky E. Glucocerebrosidase is present in 
α‑synuclein inclusions in Lewy body disorders. Acta Neuropathol. 2010;120(5):641-9. 
12. Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, et al. Effect of oral 
eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized 
clinical trial. JAMA. 2015 Feb;313(7):695-706. 

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13. Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, et al. Eliglustat 
compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme 
replacement therapy: a phase 3, randomised, open-label, non-inferiority trial.  Lancet. 2015 
Jun;385(9985):2355-62. 
14. Sardi SP, Clarke J, Viel C, Chan M, Tamsett TJ, Treleaven CM, et al. Augmenting CNS 
glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-
related synucleinopathies. Proc Natl Acad Sci U S A. 2013 Feb;110(9):3537-42. 
15. Postuma RB, Gagnon JF, Bertrand JA, Genier Marchand D, Montplaisir JY. Parkinson risk in 
idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology. 
2015;84:1104-1113. 
 
 
 

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17 
APPENDICES 
Appendix A 
List of common GBA mutations 
Note: If the patient has a GBA mutation that is not on the list, a consult will always be required to 
determine the eligibility of the patient and severity of the novel variant.  
Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
Severe GBA Mutations 
Frameshifts 
122CC 
122insC  
Arg41ProfsX6 
148-149insGTAT 
148-149insGTAT 
Tyr50CysfsX15 
203Cdel 
203delC 
Pro68ArgfsX23 
329–333del CAGAA 
329–333del CAGAA 
Not determined 
330delA 
330delA 
Glu111AsnfsX7 
413delC 
413delC 
Pro138LeufsX62 
493insA 
493insA 
Not determined 
500insT 
500insT  
Ser168LeufsX12 
532delC 
532delC  
Not determined 
534delT 
534delT 
Asp179MetfsX21 
595–596delCT 
595_596delCT 
Leu199AspfsX62 
72delC 
72delC 
Leu25SerfsX66 
V214Stop 
741delC 
Trp248GlyfsX6 
84GG 
84dupG 
Leu29AlafsX18 
898delG 
898delG 
Ala300ProfsX4 
914Cdel 
914delC 
Pro305LeufsX31 
953delT 
953delT 
Leu318ProfsX18 
Tyr343Stop 
1029delT 
Tyr343X 
1093–1094insG 
1093dupG 
Glu365GlyfsX71 
1098insA 
1098dupA 
His367ThrfsX69 
1122–1123insTG 
1121_1122dupTG 
Leu375CysfsX20 
1147delG 
1147delG  
Not determined 
119delC 
119delC 
Not determined 
1214delGC 
1214_1215delGC 
Ser405AsnfsX30 
1263–1317del 
1263–1317del 
Not determined 

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Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
1284delA 
1284delA 
GlyAspfsX15 
1326insT 
1326dupT 
Val443CysfsX26 
1447–1466del20,insTG 
1447_1466delinsTG 
Leu483_Met489delinsTrp 
Substitutions 
A190T 
685G>A 
Ala229Thr 
A190E 
686C>A 
Ala229Glu 
A341T 
1138G>A 
Ala380Thr 
A456P 
1483G > C 
Ala495Pro 
C16S 
164G > C 
Cys55Ser 
C342Y 
1142G>A 
Cys381Tyr 
D380A 
1256A>C 
Asp419Ala 
D399N 
1312G>A 
Asp438Asn 
D409H 
1342G > C 
Asp448His 
D409V 
1343A>T 
Asp448Val 
E41K 
238G>A 
Glu80Lys 
E233Stop 
814G>T 
Glu272X 
E388Stop 
1279G>T 
Glu427X 
F213I  
754T > A 
Phe252Ile 
F251L 
870C>A 
Phe290Leu 
G195E 
701G>A 
Gly234Glu 
G195W 
700G>T 
Gly234Trp 
G202R 
721G > A 
Gly241Arg 
G325R 
1090G > A 
Gly364Arg 
G355D 
1181G>A 
Gly394Asp 
G389E 
1283G>A 
Gly428Glu 
G390R 
1285G>A 
Gly429Arg 
H255Q 
882T>G 
His294Gln 
H311R 
1049A>G 
His350Arg 
I119T 
473T > C 
Ile158Thr 
I402F 
1321A>T 
Ile441Phe 
K74Stop 
337A>T 
Lys113X 
K157Q 
586A>C 
Lys196Gln 
K157N 
588G>T 
Lys196Asn 
K198E 
709A>G 
Lys237Glu 

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Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
K425E 
1390A>G 
Lys464Glu 
L197F 
706C>T 
Leu236Phe 
L240P 
836T>C 
Leu279Pro 
L385P 
1271T>C 
Leu424Pro 
L444P  
1448T>C 
Leu483Pro 
L444R 
1448T>G 
Leu483Arg 
N392I 
1292A>T 
Asn431Ile 
N462K 
1503C>G 
Asn501Lys 
P178S 
649C > T 
Pro217Ser 
P182L 
662C > T 
Pro221Leu 
P266L 
914C>T 
Pro305Leu 
P415R 
1361C>G 
Pro454Arg 
Q73Stop 
334C>T 
Gln112X 
Q169Stop 
622C>T 
Gln208X 
Q350Stop 
1165C>T 
Gln389X 
Q414Stop 
1357C>T 
Gln453X 
Q414R 
1358A>G 
Gln453Arg 
R47Stop 
256C>T 
Arg86X 
R120W 
475C>T 
Arg159Trp 
R120Q 
476G > A 
Arg159Gln 
R131C 
508C > T 
Arg170Cys 
R131L 
509G > T 
Arg170Leu 
R163Stop 
604C>T 
Arg202X 
R257Q  
887G > A 
Arg296Gln 
R257Stop   
886C>T 
Arg296X 
R285H 
971G > A 
Arg324His 
R353G 
1174C>G 
Arg392Gly 
R359Stop 
1192C>T 
Arg398X 
R463C 
1504C > T 
Arg502Cys 
R463Q 
1505G>A 
Arg502Gln 
S107L 
437C > T 
Ser146Leu 
S173Stop 
635C>G 
Ser212X 
S237P 
826T>C 
Ser276Pro 
S364R 
1207A>C 
Ser403Arg 

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Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
T231R 
809C>G 
Thr270Arg 
T491I 
1589C > T 
Thr530Ile 
V394L 
1297G > T 
Val433Leu 
V398L 
1309G>C 
Val437Leu 
V398F 
1309G>T 
Val437Phe 
W179Stop 
653G>A 
Trp218X 
W(-4)Stop 
108G>A 
Trp36X 
W378Stop 
1250G>A 
Trp417X 
Y135Stop 
522T>A  
Tyr174X 
Y304C 
1028A>G 
Tyr343Cys 
Y304Stop 
1029T>G 
Tyr343X 
841-842insTGA 
839_841dupTGA 
Leu280_Ser281insMet 
Splice variants 
IVS10+2t>a 
1505+2t>a 
Not determined 
IVS10(+2) 
1505+2t>g 
Not determined 
IVS2+1g>a 
115+1g>a 
Not determined 
IVS2+1g>t 
115+1g>t 
Not determined 
(-203)a>g + IVS4-2a>g 
(-203a>g; 455-2a>g) 
Not determined 
IVS5+1g>t 
588+1g>t 
Not determined 
Other GBA Mutations 
222-224delTAC 
222_224del TAC 
Thr75del 
A90T 
385G>A 
Ala129Thr 
A232G 
812C>G 
Ala271Gly 
C342G 
1141T>G 
Cys381Gly 
C342R 
1141T>C 
Cys381Arg 
D127V 
497A>T 
Asp166Val 
D140H 
535G > C 
Asp179His 
D409G 
1343A>G 
Asp448Gly 
F37V 
226T>G 
Phe76Val 
F216Y 
764T>A 
Phe255Tyr 
F397S 
1307T>C 
Phe436Ser 
G46E 
254G > A 
Gly85Glu 
G189V 
683G > T 
Gly228Val 
G193W 
694G>T 
Gly232Trp 

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Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
G377S 
1246G > A 
Gly416Ser 
G377C 
1246G>T 
Gly416Cys 
I402T 
1322T>C 
Ile441Thr 
K79N 
354G>C 
Lys118Asn 
K413Q 
1354A>C 
Lys452Gln 
L66P 
314T>C 
Leu105Pro 
L371V 
1228C>G 
Leu410Val 
M123V 
484A > G 
Met162Val 
N117D 
466A > G 
Asn156Asp 
N188R 
680_681 delinsGG 
Asn227Arg 
N188S 
680A > G 
Asn227Ser 
N370S 
1226A > G 
Asn409Ser 
N396T 
1304A>C 
Asn435Thr 
P122S 
481C>T 
Pro161Ser 
P159L 
593C > T 
Pro198Leu 
P159T 
592C > A 
Pro198Thr 
P266R 
914C > G 
Pro305Arg 
P289L 
983C>T 
Pro328Leu 
P401L 
1319C>T 
Pro440Leu 
R48W 
259C > T 
Arg87Trp 
R170C 
625C>T 
Arg209Cys 
R170P 
626G>C 
Arg209Pro 
R359Q 
1193G>A 
Arg398Gln 
R395C 
1300C>T 
Arg434Cys 
R433G 
1414A>G 
Arg472Gly 
R496C 
1603C>T 
Arg535Cys 
R496H 
1604G>A 
Arg535His 
S271G 
928A>G 
Ser310Gly 
S271N 
929G>A 
Ser310Asn 
S364T 
1208G>C 
Ser403Thr 
S364N 
1208G>A 
Ser403Asn 
S366G 
1213A>G 
Ser405Gly 
T43I 
245C>T 
Thr82Ile 
T134I 
518C>T 
Thr173Ile 

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Category 
Allele Name 
cDNA nucleotide 
substitution 
Amino Acid 
substitution 
T323I 
1085C>T 
Thr362Ile 
V15L 
160G>T 
Val54Leu 
V352L 
1171G>C 
Val391Leu 
V375L 
1240G>T 
Val414Leu 
V375G 
1241T>G 
Val414Gly 
W184R 
667T>C 
Trp223Arg 
W312C 
1053G>T 
Trp351Cys 
W378G 
1249T>G 
Trp417Gly 
Sequence variants where 
history of RBD or co-
occurrence of any mutation 
on the list are required 
E326K 
1093G>A 
Glu365Lys 
T369M 
1223C>T 
Thr408Met 
Note: If the patient has a GBA mutation that is not on this list, a consult will be required to determine the eligibility of the patient. 
Abbreviation: cDNA: complementary deoxyribonucleic acid; GBA: β-glucocerebrosidase gene; RBD: rapid eye movement sleep behavior 
disorder. 

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Appendix B 
REM Sleep Behavior Disorder Screening Questionnaire 

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Appendix C 
Guidance on contraceptive methods and collection of pregnancy 
information 
DEFINITIONS 
Nonreproductive potential 
1. Premenopausal female with 1 of the following: 
NOTE: Documentation can come from the review of subject’s medical records, medical 
examination, or medical history interview. 
- 
Documented hysterectomy. 
- 
Documented bilateral salpingectomy. 
- 
Documented bilateral oophorectomy. 
2. Postmenopausal 
- 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.  
- 
Females on HRT and whose menopausal status is in doubt will be required to use 1 of 
the highly effective contraception methods if they wish to continue their HRT during 
the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrolment. 
Reproductive potential (WOCBP) 
A woman is considered of reproductive potential (WOCBP), ie, fertile, following menarche and 
until becoming postmenopausal unless permanently sterile. Permanent sterilization methods 
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. 
CONTRACEPTIVE GUIDANCE 
Male subjects 
• Male subjects with heterosexual partners of reproductive potential (WOCBP) are eligible 
to participate if they agree to use the following during the protocol defined timeline: 
- 
Refrain from donating sperm  
and 
- 
At least 1 of the following conditions applies: 
- 
Are and agree to remain abstinent from penile-vaginal intercourse on a long-term 
and persistent basis, when this is their preferred and usual lifestyle.  

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or 
- 
Agree to use a male condom plus an additional contraceptive method with a failure 
rate of 1% per year (see table for female subjects). 
• Men with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom for the time defined in the protocol. 
Highly Effective Contraceptive Methods That Are User Dependent 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
- 
oral 
- 
intravaginal 
- 
transdermal 
• Progestogen-only hormone contraception associated with inhibition of ovulation 
- 
oral 
- 
injectable 
Highly Effective Methods That Are User Independent 
• Implantable progestogen-only hormone contraception associated with inhibition of ovulation 
• Intrauterine device  
• Intrauterine hormone-releasing system  
• Bilateral tubal occlusion 
• Vasectomized partner 
• Sexual abstinence 
 
Female subjects: 
Highly Effective Contraceptive Methods That Are User Dependent 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
- 
oral 
- 
intravaginal 
- 
transdermal 

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• Progestogen-only hormone contraception associated with inhibition of ovulation 
- 
oral 
- 
injectable 
Highly Effective Methods That Are User Independent 
• Implantable progestogen-only hormone contraception associated with inhibition of ovulation 
• Intrauterine device  
• Intrauterine hormone-releasing system  
• Bilateral tubal occlusion 
• Vasectomized partner 
• Sexual abstinence 
Male subjects with partners of reproductive potential who become pregnant  
• The Investigator will attempt to collect pregnancy information on any female partner of a 
male study subject who becomes pregnant while participating in this study. This applies 
only to subjects who receive study treatment. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy.  
• Partner will also be followed to determine the outcome of the pregnancy. Information on 
the status of the mother and child will be forwarded to the Sponsor.  
• Generally, follow-up will be no longer than 6 to 8 weeks following the estimated delivery 
date. Any termination of the pregnancy will be reported regardless of fetal status (presence 
or absence of anomalies) or indication for procedure.  
Female subjects who become pregnant  
• The Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study.  
• Information will be recorded on the appropriate form and submitted to the Sponsor within 
24 hours of learning of a participant's pregnancy.  
• Participant will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on participant and neonate, which will be forwarded to 
the Sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks beyond 
the estimated delivery date.  Additional follow-up information may be requested about the 

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baby until at least one year after the birth of the baby, due to potential risk of abnormalities 
not present at birth.  
• Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy will be reported as an AE or SAE.  
• A spontaneous abortion is always considered to be an SAE and will be reported as such. 
 

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Appendix D 
Drugs that can prolong the QT interval 
Antimicrobials 
Antipsychotics (all have some risk) 
 
Erythromycin 
 
Risperidone 
 
Clarithromycin 
 
Fluphenazine 
 
Moxifloxacin 
 
Haloperidol 
 
Fluconazole 
 
Pimozide 
 
Ketoconazole 
 
Chlorpromazine 
Antiarrhythmics 
 
Quetiapine 
 
Dronedarone 
 
Clozapine 
 
Sotalol 
Antidepressants 
 
Quinidine 
 
Citalopram/escitalopram 
 
Amiodarone 
 
Amitriptyline 
 
Flecainide 
 
Clomipramine 
 
 
Dosulepin 
Others 
 
Doxepin 
 
Methadone 
 
Imipramine 
 
Protein kinase inhibitors, eg, sunitinib 
 
Lofepramine 
 
Some antimalarials 
Antiemetics 
 
Some antiretrovirals 
 
Domperidone 
 
Telaprevir 
 
Droperidol 
 
Boceprevir 
 
Ondansetron/Granisetron 
 
NOTE: This list is not exhaustive but is designed to give examples of more commonly used drug 
classes. 
 

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Appendix E 
List of known CYP3A4 inducers/inhibitors 
Please always check/confirm against the most up-to-date list on the FDA website: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling 
CYP3A4 Inducers 
Aminoglutethimide 
Nevirapine 
Bexarotene 
Oxcarbazepine 
Bosentan 
Phenobarbital 
Carbamazepine 
Phenytoin 
Dexamethasone 
Primidone 
Efavirenz 
Rifabutin 
Fosphenytoin 
Rifampin 
Griseofulvin 
Rifapentine 
Modafinil 
St. John’s wort 
Nafcillin 
 
 
CYP3A4 Inhibitors 
Amiodarone 
Imatinib 
Amprenavir 
Indinavir 
Atazanavir 
Isoniazid 
Chloramphenicol 
Itraconazole 
Clarithromycin 
Ketoconazole 
Conivaptan 
Lapatinib 
Cyclosporine 
Miconazole 
Darunavir 
Nefazodone 
Dasatinib 
Nelfinavir 
Delavirdine 
Posaconazole 
Diltiazem 
Ritonavir 
Erythromycin 
Quinupristin 
Fluconazole 
Saquinavir 
Fluoxetine 
Tamoxifen 
Fluvoxamine 
Telithromycin 
Fosamprenavir 
Verapamil 
Grapefruit juice 
Voriconazole 

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Appendix F 
Movement Disorder Society-Unified Parkinson’s Disease Rating 
Scale, including Hoehn and Yahr 

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Appendix G 
Parkinson’s Disease-Cognitive Rating Scale 
 
 
 
 
 
 
 
 

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Appendix H 
Body fluid biomarkers 
The following biomarkers in blood, dried blood spot and/or cerebrospinal fluid may be analyzed 
in samples collected during the study, at the discretion of the Sponsor: 
 
Blood markers (plasma or serum) 
• Glucosylceramide 
• Glucosylsphingosine  
• Neurofilament light chain  
Other markers may also be assessed. 
Dried blood spot 
• Glucocerebrosidase activity 
Other markers may also be assessed. 
Cerebrospinal Fluid 
• Glucosylceramide 
• Glucosylsphingosine  
• Neurofilament light chain  
• Glucocerebrosidase activity 
• Total alpha-synuclein 
• Tau and phospho-Tau181 
• Amyloid –beta 1-40, and Amyloid –beta 1-42 
Other markers may also be assessed. 

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Appendix I 
Montreal Cognitive Assessment 

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Appendix J 
Oral Symbol Digit Modalities Test 

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Appendix K 
Trail Making Test Parts A & B  
 

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Appendix L 
Beck Depression Inventory, Second Edition  

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Appendix M 
Clinical Global Impression of Change 
 

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Appendix N 
Patient Global Impression of Change 

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Appendix O 
Parkinson's Disease Questionnaire – 39 

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Appendix P 
EuroQol Five Dimensions Questionnaire (EQ-5D) 
 

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Appendix Q 
Falls Efficacy Scale 
 

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Appendix R 
Health-Related Productivity Questionnaire (HRPQ) 
 

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Appendix S 
General guidance for the follow-up of laboratory abnormalities by 
Sanofi  
Neutrophils < 1500/mm3 or according to ethnic 
group
NEUTROPENIA
Repeat immediately a full blood count if value 
close to 1500/mm3
Neutrophils < 1500/mm3 confirmed 
with signs of infection  
Neutrophils < 1500/mm3 confirmed 
with no signs of infection  
1.
DISCONTINUE
Investigational Medicinal 
Product, hospitalization 
should be considered
2.
PERFORM biological 
investigations for infection
1.
DISCONTINUE
Investigational 
Medicinal Product
2.
INVESTIGATE for 
infection
In both situations
3.
INFORM the local monitor
4.
INVESTIGATE previous treatments particularly long-term, even a long time ago, 
exposure to toxic agents, e.g., benzene, X-rays, etc.
5.
PERFORM and collect the following investigations (results): 
•
RBC and platelet counts
•
Serology: EBV, (HIV), mumps, measles, rubella
6.
DECISION for bone marrow aspiration: to be taken in specialized unit
7.
COLLECT/STORE one sample following handling procedures described in PK 
sections (for studies with PK sampling) and freeze one serum sample (5 mL) on 
Day 1 (cessation of investigational medicinal product) and Day 5 (for further 
investigations)
8.
MONITOR the leukocyte count 3 times per week for at least one  week, then twice a 
month until it returns to normal
Note: 
•The procedures described in the above flowchart are to be discussed with the patient only in case 
the event occurs. If applicable (according to local regulations), an additional consent (e.g., for 
HIV testing) will only be obtained in the case the event actually occurs.
•For individuals of African descent, the relevant value of concern is <1000/mm3
Neutropenia is to be recorded as AE only if at least one of the criteria listed in Section 10.4.3 is met
 
Neutropenia is to be recorded as an AE only if at least 1 of the criteria listed in the general 
guidelines for reporting AEs in Section 10.4.2 is met. 

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Platelets < 100 000/mm3 (rule out EDTA – induced 
pseudo-thrombocytopenia)
THROMBOCYTOPENIA
Repeat immediately the count (rule out EDTA 
anticoagulant in the sample)
Platelets  < 100 000/mm3 confirmed 
with bleeding  
Platelets  < 100 000/mm3 confirmed 
with no bleeding
1.
DISCONTINUE
Investigational Medicinal 
Product
2.
HOSPITALIZATION
should be considered
1.
DISCONTINUE
Investigational Medicinal 
Product
2.
INVESTIGATE for 
bleeding
In both situations
3.
INFORM the local Monitor
4.
QUESTION about last intake of quinine (drinks), alcoholism, heparin administration
5.
PERFORM or collect the following investigations: 
•
Complete blood count, schizocytes, creatinine
•
Bleeding time and coagulation test (fibrinogen, INR or PT, aPTT), Fibrin 
Degradation Product
•
Viral serology: EBV, HIV, mumps, measles, rubella
6.
COLLECT/STORE one sample following handling procedures described in PK 
sections (for studies with PK sampling) and freeze one serum sample (5 mL) on 
Day 1 (cessation of investigational medicinal product) and Day 5 (for further 
investigations)
7.
DECISION for bone marrow aspiration: to be taken in specialized unit
•
On Day 1 in the case of associated anemia and/or leukopenia
•
On Day 8 if platelets remain < 50 000/mm3
8.
MONITOR the platelet count every day for at least one week and then regularly 
until it returns to normal
Note: 
The procedures above flowchart are to be discussed with the patient only in case described in the 
the event occurs. If applicable (according to local regulations), an additional consent (e.g., for 
HIV testing) will only be obtained in the case the event actually occurs.
Thrombocytopenia is to be recorded as AE only if at least one of the criteria listed in Section 10.4.3 
is met
 
Thrombocytopenia is to be recorded as an AE only if at least 1 of the criteria listed in the general 
guidelines for reporting AEs in Section 10.4.2 is met. 

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*If unable to retest in 72 hours, use original lab results to decide on further reporting/monitoring/discontinuation.  
Note: 
• “Baseline” refers to ALT sampled at baseline visit; or if baseline value unavailable, to the latest ALT sampled 
before the baseline visit. The algorithm does not apply to the instances of increase in ALT during screening. 
• See Section 10.4 for guidance on safety reporting. 
• Normalization is defined as ≤ ULN or baseline value, if baseline value is >ULN. 
INCREASE IN ALT
ALT > 3 ULN
Confirm ALT > 3 ULN
Retest within 72 hours of initial 
sample*
No
Yes
COMPLETE the specific CRF forms for 
„ALT Increase” and inform the 
Monitoring Team within 24 hours
Total Bilirubin > 2 ULN 
No
Yes
ALT > 5 ULN (if baseline ALT ≤ 2 ULN), or 
ALT >8 ULN (if baseline ALT > 2 ULN)
Continue IMP administration
No
Monitor LFTs every 72 hours
IMP administration can be continued as 
long as – under close monitoring –
conditions for permanent 
discontinuation or temporary 
interruption per protocol are not met
Yes
Permanent Discontinuation of IMP
In ANY CASE, FOLLOW the instructions listed in the box below: 
1.
INFORM the Site Monitor who will forward the information to the Study Manager
2.
INVESTIGATE specifically for malaise with or without loss of consciousness, dizziness, and/or hypotension and/or episode of 
arrhythmia in the previous 72 hours; rule out muscular injury
3.
PERFORM the following tests:
- LFTs: AST, ALT, alkaline phosphatase, total and conjugated bilirubin and prothrombin time / INR
- CPK, serum creatinine, complete blood count
- Anti-HAV IgM, anti-HBc IgM (HBV-DNA if clinically indicated), anti-HCV and HCV RNA, anti-
CMV  IgM and anti-HEV IgM antibodies
- Depending on the clinical context, check for recent infection with EBV, herpes viruses, and toxoplasma
- Hepatobiliary ultrasonography (or other imaging investigations if needed)
4.
CONSIDER Auto-antibodies: antinuclear, anti-DNA, anti-smooth muscle, anti-LKM
5.
CONSIDER consulting with hepatologist
6.
CONSIDER patient hospitalisation if INR>2 (or PT<50%) and/or central nervous system disburbances suggesting hepatic 
encephalopathy
7.
MONITOR LFTs after discontinuation of IMP:
- As closely as possible (or every 48 hours) until stabilization, then every 2 weeks until return to normal/baseline or clinical 
resolution.
8.
FREEZE serum sample (5ml x 2)
9.
In case of SUSPICION of GILBERT Syndrome, a DNA diagnostic test should be done

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Rapid increase in serum creatinine over 150 µmol/L 
or rapid decrease in creatinine clearance below
50 mL/mn
ACUTE RENAL FAILURE
Can be rapidly reversed:
• By volume repletion
• Or relief of urinary tract 
obstruction (according to etiology)
Cannot be rapidly reversed: 
• Occurrence/aggravation of life 
threatening symptoms of ARF: anemia, 
hyperkalemia, hyperuricemia, metabolic 
acidosis, cardiac insufficiency, 
pulmonary edema, arrhythmia, DIC, etc.
• And/or predominant elimination of 
Investigational Medicinal Product by 
renal route
1.
Investigational Medicinal 
Product may be continued
2.
MONITOR serum creatinine 
until return to baseline level
1.
INFORM the local monitor
2.
DISCONTINUE
Investigational Medicinal Product 
administration
3.
HOSPITALIZATION should be 
considered and seek for nephrologic  
advice
4.
PERFORM the following 
examinations: 
•
BP, HR, hydration status, ECG
•
Blood count
•
Liver function tests + CPK
•
Biochemistry, including urea
•
Urinalysis
5.
COLLECT/STORE one sample 
following handling procedures 
described in PK sections (for studies 
with PK sampling) and freeze one 
serum sample (5 mL) on Day 1 
(cessation of investigational 
medicinal product)
6.
MONITOR renal function until 
return to baseline level (every day at 
the beginning, then every week)
Acute renal failure is to be recorded as AE only if at least one of the criteria listed in 
Section 10.4.3 is met
 
Acute renal failure is to be recorded as an AE only if at least 1 of the criteria listed in the general 
guidelines for reporting AEs in Section 10.4.2 is met. 

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If Increase in CPK (expressed in ULN)
> 3 ULN
Repeat immediately the count.
If confirmed, inform the local monitor and
INVESTIGATE for the origin:
- PERFORM:
•
ECG
•
CPK-MB -MM 
•
Troponin
•
Creatinine
•
Iono (k+, Ca2+)
•
Transaminases + Total and conjugated bilirubin
•
Myoglobin (serum and urines)
- COLLECT/STORE one sample following handling procedures described in PK sections (for 
studies with PK sampling) and freeze one serum sample (5 mL) on Day 1 (cessation of 
investigational medicinal product). 
- INTERVIEW the patient about a recent intensive muscular effort, trauma, convulsions, electrical 
injury, injury or stress to the skeletal muscle, multiple intramuscular injections, recent surgery, 
concomitant medications, consumption of alcohol, morphine, cocaine.
- SEARCH for alternative causes to cardiac or muscular toxicity, ie: stroke, pulmonary infarction, 
dermatomyositis or polymyositis, convulsions, hypothyroidism, delirium tremens, muscular 
dystrophies.
If either the cardiac origin or the 
rhabdomyolysis is confirmed or if CPK 
> 10 ULN:
1. DISCONTINUE Investigational 
Medicinal Product administration
2. MONITOR CPK every 3 days for the 
first week then once weekly until return 
to normal or for at least 3 months
3. HOSPITALIZATION should be 
considered
If the cardiac origin or the rhabdomyolysis is 
ruled out and if CPK 10 ULN:
MONITOR CPK every 3 days for the first week 
then once weekly until return to normal or for 
at least 3 months
Muscular symptoms (myalgia, pain, weakness, 
dark urines)
Systematic CPK assessment as per 
protocol
Perform CPK
SUSPICION OF RHABDOMYOLYSIS
Suspicion of rhabdomyolysis is to be recorded as AE only if at least one of the criteria listed in Section 10.4.3 
is met
 
Suspicion of rhabdomyolysis is to be recorded as an AE only if at least 1 of the criteria in the 
general guidelines for reporting AEs in Section 10.4.2 is met. 

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Appendix T 
Country-specific requirements  
The country-specific requirements for Japan and Israel are included in the protocol in the relevant 
sections, and the rationale for the amendment is included in Appendix U (Protocol amendment 
history). 

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Appendix U 
Protocol amendment history 
The Protocol Amendment Summary of Changes for the current amendment is located directly 
before the Clinical Trial Summary. 
Amended clinical trial protocol 05 (03 September 2020) 
This amended protocol (amendment 05) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The protocol is being amended to include a 1-year prolongation of the open-label long-term 
follow-up period (Period 3) of Part 2. This prolongation is being done to allow time for analysis of 
the results from the 52-week double blind period (planned for Q1 2021) to inform the potential 
long-term extension program. 
Protocol amendment summary of changes table 
Section # and Name 
Description of 
Change 
Brief Rationale 
Clinical trial summary, Study design, Assessment schedule, 
Duration of study period (per patient); Section 1.2, Graphical study 
design for Part 2; Section 1.3.3, Part 2: study schedule of 
assessments (Periods 3 and 4); Section 6.1, Description of the 
study; Section 6.2.1, Duration of study participation for each 
patient; Section 6.2.2, Determination of end of clinical trial (all 
patients); Section 6.5, Discussion of study design; Section 8.1, 
Investigational medicinal product; Section 8.3.2, Randomization 
code breaking during Parts 1 and 2; Section 9.1.2, Part 2: 
Treatment phase; Section 9.2.3.1, Parkinson’s disease-cognitive 
rating scale; Section 9.3.3.3, Vital signs; Section 9.3.3.4, Physical 
examination; 9.3.3.5, Neurological examination; 9.3.3.6, 
Ophthalmological examination; Section 9.3.3.7, Electrocardiogram 
(ECG); Section 9.4.3, Dopamine transporters scan assessment; 
Section 9.4.5.1, Montreal cognitive assessment score; Section 
9.4.5.2, Oral symbol digit modalities test score; Section 9.4.5.3, 
Trail making test A and B score; 9.4.5.4, Beck depression 
inventory, second edition; Section 9.4.5.7, Parkinson’s disease 
questionnaire – 39 score; Section 9.4.5.8, EuroQol five 
dimensions questionnaire; Section 9.4.5.9, Falls efficacy scale; 
Section 9.5, Health-related productivity questionnaire; Section 
10.1.2.10, Long term follow-up period (Period 3); Section 
10.1.2.11, Six-week follow-up visit (Period 4, end-of-study visit, 
Visit 16: Week 214 ± 7 days); Section 10.3.3, List of criteria for 
permanent treatment discontinuation; Section 10.3.4, Handling of 
patients after permanent treatment discontinuation; Section 10.3.5, 
Procedure and consequence for patient withdrawal from study, 
Section 11.5.2, Two-step final analysis 
Sections updated. 
 
 
 
 
 
 
 
To add the supplementary 
visits and corresponding 
assessments related to the 
1-year prolongation of the 
long-term follow-up period 
(Period 3). 
 
 
 
 
 
 
 
Clinical trial summary, Study objectives, Endpoints; Section 5.2.3 
Update of the exploratory 
To clarify the objectives of the 

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Section # and Name 
Description of 
Change 
Brief Rationale 
Exploratory objectives  
study objectives. 
 
long-term follow-up period 
(period 3). 
Clinical trial summary, Assessment schedule; Section 1.3.3, 
Part 2: Study schedule of assessments (Periods 3 and 4); 
Section 6.2.2, Determination of end of clinical trial (all patients); 
Section 10.1.2.10, Long term follow-up period (Period 3) 
Sections updated. 
To specify that Visit 15 
(Week 208) will be the last 
study visit for patients who will 
transition to a long-term study 
with GZ/SAR402671. 
Section 6.5, Discussion of study design  
Revised text regarding 
Parkinson’s disease (PD) 
medications. 
To clarify the PD medications 
allowed during the study. 
Section 13.2, Responsibilities of the Sponsor 
Added text stating the 
monitoring may include 
remote monitoring, and 
details are provided in 
separate documents. 
Sanofi protocol template 
update, adapting to the 
changing trial environment. 
Throughout 
Administrative changes. 
Minor, therefore not 
summarized. 
 
Amended clinical trial protocol 04 (21 May 2020) 
This amended protocol (amendment 04) is considered to be non-substantial based on the criteria 
set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The protocol is being amended to remove the interim analysis, to include guidance for Covid-19 
pandemic, to incorporate feedback received from the Investigator(s), as well as other changes 
deemed necessary by the Sponsor.  
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Clinical Trial Summary (Study 
objectives, Endpoints), Section 5.2.3, 
Exploratory Objectives; New Section 
9.4.6, Parkinson’s disease 
progression model 
Added a new exploratory objective and 
endpoint. 
To better characterize Parkinson’s 
disease (PD) progression in early stage 
PD patients carrying a 
β-glucocerebrosidase gene (GBA) 
mutation. 
Clinical Trial Summary (Statistical 
considerations), Section 6.3, Interim 
Analysis; Section 11.5.1, Interim 
Efficacy Analysis 
Removed interim analysis. 
Interim analysis planned for 
administrative purposes that are no 
longer required by the Sponsor. 
Section 1.3.2, Part 2: Study schedule 
of assessments (Periods 1 and 2), 
Added text to address Covid-19 pandemic. 
To provide guidance during Covid-19 
pandemic. 

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Section # and Name 
Description of Change 
Brief Rationale 
footnote “u”; Section 1.3.3, Part 2: 
Study schedule of assessments 
(Periods 3 and 4), footnote “f”; 
Section 8.8.1.1, Temporary use of 
strong or moderate CYP3A4 inducers 
or inhibitors; Section 10.1.2, Part 2: 
Treatment phase; New Section 
10.1.2.12, Contact for IMP dispensing 
during Covid-19 outbreak 
Section 4.2.2, Risk assessment 
Updated section.  
Last information regarding 
gastrointestinal, liver and central 
nervous system safety data were 
added. 
Section 8.7, Responsibilities 
Added text regarding Direct-to-Patient 
investigational medicinal product (IMP) 
delivery. 
To avoid treatment discontinuation in 
exceptional cases, under regional or 
national emergencies (eg, natural 
disaster, epidemic diseases (eg, Covid-
19 pandemic), terrorist attack). 
Clinical Trial Summary (Assessment 
schedule); Section 1.3.2, Part 2: 
Study schedules of assessments 
(Periods 1 and 2); Section 1.4.2, Part 
2: Treatment phase; Section 10.1.2, 
Part 2: Treatment Phase (Visit 
Window); Section 10.1.2.9, Visit 9: 
Week 52 (± 14 days) 
Week 52 visit window increased. 
To facilitate site organization. 
Section 8.8, Concomitant medication; 
Section 8.8.5, Medications that can 
prolong the QT interval 
Specified the forbidden concomitant treatment 
during the study. 
Protocol clarification. 
Section 10.3.3, List of criteria for 
permanent treatment discontinuation; 
Section 10.3.4, Handling of patients 
after permanent treatment 
discontinuation; Section 10.3.5, 
Procedure and Consequence for 
Patient Withdrawal From Study 
Specified the patient management in case of 
study/treatment discontinuation 
Protocol clarification. 
Section 8.8.3, Medications with risk 
for dopamine transporters scan 
imaging 
Revised the paragraph to match E 26 
criterion. 
Correction. 
Section 9.6.1, Optional stored DNA 
sample (not applicable in Israel); 
Section 1.3.2, Part 2: Study schedule 
of assessments (Periods 1 and 2); 
Section 10.1.2.9, Visit 9: Week 52 
(± 14 days) 
Second optional sample added. 
To better characterize drug response. 
Section 9.4.2.1.1, Lumbar puncture 
Deleted reference to an Operations Manual. 
There is no Operations Manual for this 
study. 
Section 1.3.2, Part 2: Study schedule 
of assessments (Periods 1 and 2); 
Clinical global impression scale (CGI) 
removed  from Weeks 13, 26, and 39 in Part 
Correction. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3.3, Part 2: Study schedule 
of assessments (Periods 3 and 4); 
Section 10.1.2.6, Visit 6: Week 13 
(± 3 days); Section 10.1.2.7, Visit 7: 
Week 26 (± 3 days); Section 10.1.2.8, 
Visit 8: Week 39 (± 3 days); Section 
10.1.2.10, Long term follow-up period 
(Period 3) 
2 Period 2, and from all visits in Part 2 
Periods 3 and 4. 
Section 7.2.3, Exclusion criteria 
related to current knowledge of 
GZ/SAR402671 IMP 
Updated section. 
Medical/surgical history and 
previous/concomitant medication data 
not required for screen failures. 
Section 9.3.3.6, Ophthalmological 
Examination 
Week 39 added as an intermediate time point. 
Protocol clarification. 
Section 10.1.2.2, Visit 2: 
Randomization/baseline at 
Week 0/Day 1; Section 10.1.2.9, Visit 
9: Week 52 (± 14 days);  
“Should” replaced by “must” for the order of 
assessments. 
Protocol clarification. 
Section 10.1.2.9, Visit 9: Week 52 
(± 14 days) 
Added text to provide more guidance on 
transition to long-term follow-up. 
Protocol clarification. 
Section 10.4.5, Guidelines for 
management of specific laboratory 
abnormalities 
Table 5: Updated table for Symptomatic 
overdose with IMP for which a specific form is 
to be completed. 
Correction. 
Section 10.4.3, Instructions for 
reporting serious adverse events 
Section 17, Appendices: Appendix A, 
List of common GBA mutations 
Copies of medical records only sent upon 
request by the Sponsor. 
Administrative change. 
Revised to include new GBA mutations. 
Updated with the last known mutations. 
Throughout 
Administrative changes. 
Minor, therefore not summarized. 
 
Amended clinical trial protocol 03 (Global) (20 July 2018) 
This amended protocol is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The protocol is being amended to incorporate feedback received from the Investigator(s), as well 
as other changes deemed necessary by the Sponsor.  
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Names and addresses 
Updated address of Sponsor. 
Editorial correction. 
Synopsis (study design, assessment 
Extended screening period duration from 45 
Up to 30 days is required to obtain the 

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Section # and Name 
Description of Change 
Brief Rationale 
schedule, duration of study period) 
 
Sections 1.1 and 1.2 Graphical study 
design Part 1 and Part 2 
 
Sections 1.3.1 and 1.3.2 Study 
schedule of assessment Part 1 and 
Part 2  
 
Section 6 Study design 
 
to 60 days. 
genetic laboratory results, and the 
screening is split in 2 steps. The 
objective to increase the final 2 weeks 
to 4 weeks to give more time to the 
sites to perform all remaining 
examinations including MRI and DAT 
scan. This will facilitate the logistics of 
the screening period and may prevent 
protocol deviation. 
Section 1.3.1 Part 1: Study schedule of 
assessment 
Ophthalmologic examination added at the 
early withdrawal Visit 8 (Week 8). 
Aligned flowchart footnote description 
with visit assessment.   
Section 1.3.2 Part 2: Study schedule of 
assessment 
Footnote “c” updated and added following 
details ‘genetic screening will not need to be 
repeated to confirm eligibility of patients from 
Part 1 to enroll in Part 2’.   
  
Provided clarification that the genetic 
screening does not need to be 
repeated for patients from Part 1 being 
screened for Part 2. 
Synopsis (exclusion criteria) 
 
Section 7.2.3 Exclusion criteria related 
to current knowledge of 
GZ/SAR402671 IMP 
 
Updated the exclusion criteria 26 (E 26) and 
revised the list of the drugs that have the 
potential to interfere with DATSCAN imaging 
based on the  DATSCAN USPI.  
List of drugs updated to follow 
DATSCAN label.  
Section 9.3.3.6 Ophthalmological 
examination 
“baseline visit” replaced by “screening visit”. 
Clarify that in both study parts, the first 
ophthalmological examination must be 
performed during screening (and not 
“at baseline”, which corresponds to the 
randomization visit on Week 0/Day1). 
 
Section 10.1.1.9 Visit 9 (safety 
follow-up completion visit; ± 3 days) 
Text in section 10.1.1.9 is aligned with the 
corresponding flowchart footnote 
Flowchart footnote was updated in the 
last amendment, corresponding text in 
other sections aligned with updated 
footnote.  
 
Synopsis (assessment schedule) 
 
Section 10.3.5 Procedure and 
consequence for patient withdrawal 
from study 
Added following additional details: If the 
following examinations including lumbar 
puncture, DAT scan, and PK analyses on 
plasma and CSF have been performed 
recently, then the Investigator can discuss 
with Sponsor the need to repeat these 
examinations. Repeat examination(s) will be 
done on a patient by patient basis. 
Provided more clarification on 
examinations to be performed at early 
end of treatment or withdrawal from 
Part 2. 
Appendix A 
Deleted the reference to an operation 
manual.  
Updated the mutation table and added 
T369M variant where history of RBD is 
required. 
There is no such operational manual in 
the study. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 17 Appendix  
Added 2 new appendix, Appendix T Country 
specific requirements and Appendix U 
Protocol amendment history.  
To add country specific requirements 
and prior amendment history. 
Throughout 
Minor editorial, typographical error 
corrections and document formatting 
revisions 
Minor, therefore have not been 
summarized. 

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Amended protocol 05: 06-Jun-2017 
This amended protocol (Amendment 05) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment 
The protocol is being amended mainly to incorporate feedback received from Investigators to 
facilitate enrollment and clarify some sections. 
Major changes specific to this global amendment include the following: 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Clinical Trial Summary 
(Study population, Inclusion 
Criteria);  
Section 4.2.1 Study 
rationale 
Section 7.1 Inclusion 
criteria 
Inclusion criteria I 03 updated: Increase the 
patient upper age limit from 70 to 80 years old. 
Given the acceptable safety and tolerability 
profile of venglustat seen in healthy volunteers 
and other patient populations at doses used in 
the current study, the average age of a 
Parkinson’s disease patient, and Parkinson’s 
disease guidelines within certain countries, it 
is appropriate to increase the upper age limit 
from 70 to 80 years in this trial. 
Clinical Trial Summary 
(Study population, 
Exclusion Criteria);  
Section 7.2.2 Exclusion 
criteria 
Section 7.2.3 Exclusion 
criteria 
Revise exclusion criterion E 20 to specify the 
prohibited duration of medication use. 
 
Specify the prohibited duration of the 
medication’s use, ie, within 30 days or 5 half-
lives, whichever is longer, prior to 
randomization 
Revise exclusion criterion E 25 to delete the 
words “of screening.” 
Delete “of screening” which was written by 
error in this exclusion criteria. 
Section 6.1 Description of 
the study 
Clarify that the internal review committee can 
comprise individuals involved in the conduct of 
the study 
Because the data reviewed by this internal 
review committee will be blinded, they will be 
reviewed by individuals from the clinical trial 
team involved in the study conduct. 
Throughout 
• 
Minor editorial changes to punctuation, 
grammar, and syntax. 
• 
Table of contents were updated. 
• 
Flow charts were updated to reflect the 
study procedures in Section 10. 
• 
Sections, table footnotes and citations, 
and references were renumbered. 
• 
Tables were reformatted. 
• 
Abbreviations were updated in text, 
Section 3 (Abbreviations), and table 
footnotes. 
• 
References were updated. 
Minor, therefore have not been summarized. 
 

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Amended protocol 04 (local for Japan): 01-Feb-2017 
This amended protocol (Amendment 04) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment 
The protocol is being amended primarily to incorporate feedback received from Health 
Authorities on the clinical trial notification in Japan. 
Major changes specific to Japan sites include the following: 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Clinical Trial Summary 
(Assessment Schedule);  
Section 1.2 Graphical study 
design; 
Section 1.3.3 Part 2: Study 
schedule of assessment 
(Period 3 and 4); 
Section 9.3.3.3 Vital signs; 
Section 10.1.2.10 Long-
term follow-up period 
(Period 3) 
Change the visit interval, as every 3 months in 
the long-term follow up period in Part 2 is only for 
Japanese patients. 
Additional visits (W65, W91, W117, and 
W143), for Japanese patients only, between 
the 6 month follow-up visits in the LTFU 
(Period 3) of Part 2 are added so Japanese 
patient safety can be monitored by a 
healthcare professional every 3 months. 
Section 1.3.1 Part 1 Study 
schedule of assessments; 
Section 10.1.1.2 Visit 2: 
Randomization/baseline at 
Week 0/Day 1 
Changes in description of hospitalization from 
Visit 2 through Visit 4 in Part 1 for Japanese 
patients. 
To ensure Japanese patients’ safety in the 
beginning of the treatment period in Part 1 
(dose escalation phase). 
Section 4.2.2 Risk 
assessment 
Addition of the new information to the risk 
assessment. 
The delayed development of fetus and related 
findings in the skeletal system in the non-
clinical toxicology study on embryo-fetal 
development were added as the information to 
be shared. 
Section 8.8.1.1 Temporary 
use of strong or moderate 
CYP3A4 inducers or 
inhibitors;  
Section 10.3.3 List of 
criteria for permanent 
treatment discontinuation 
Specified the patient management in terms of 
study drug administration rules when a temporary 
use of a strong or moderate CYP3A4 inducer or 
inhibitor is required. 
Description of the impact on study drug 
administration in case such concomitant 
medication is required was added to specify 
the patient management in terms of study 
drug administration rules. 
Appendix C 
Guidance on contraceptive methods and 
collection of pregnancy information updated. 
To provide some additional information on the 
reproductive potential of bilateral tubal ligation, 
a definition of post-menopausal state, some 
clarifications on contraceptive methods to be 
followed in both male and female during the 
study, and the non-approval status of the 

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drugs and medical device in Japan. 
Throughout 
• 
Administrative changes. 
• 
Minor editorial changes to punctuation, 
grammar, and syntax. 
• 
Sections, table footnotes and citations, 
and references were renumbered. 
• 
Tables of contents were updated. 
• 
Abbreviations were updated and were 
listed in revised Section 3, 
Abbreviations. 
Minor, therefore have not been summarized. 
 
Amended protocol 03: 08-Dec-2016 
This amended protocol (Amendment 03) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment 
The protocol is being amended to primarily incorporate feedback received from Health 
Authorities in the United States and Japan, as well as other changes deemed necessary by the 
Sponsor. Please note a separate local amendment was previously issued for patients enrolled in 
Japan and several changes from the Japan amendment are being incorporated into this global 
amendment, as applicable. 
Major changes specific to this global amendment include the following: 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Clinical trial summary 
(study population);  
Section 7.1 Inclusion 
criteria 
Section 7.2 Exclusion 
criteria 
Inclusion criteria I 01, I 02, I 03, I 05 and 
exclusion criteria E 14 updated. 
I 01. and I 02. were clarified, indicating that 
both do not need to be met in order to qualify 
(just one or the other). 
I 03. was clarified in order to appropriately 
define the Japanese adult patient population 
age range. 
I 05. was clarified to state that patients on 
stable PD medication need to be on ‘ON’ state 
when scoring the Hoehn and Yahr scale at 
baseline. 
E 14. was clarified to state forms and duration 
of contraception. 
Throughout 
• 
Administrative change. 
• 
Minor editorial changes to punctuation, 
grammar, formatting, abbreviations, 
and syntax. 
• 
Sections and table footnote 
Minor, therefore have not been summarized. 

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annotations renumbered. 
• 
In Part 2 Treatment Phase, site Visit 4 
at Week 0, Day 3 has been removed 
from Section 1.3.2 Part 2: Study 
schedule of assessments (Periods 1 
and 2) flowchart for consistency (it was 
added to original protocol in error). 
Therefore, visit numbers throughout the 
protocol have been renumbered; 
Section 10.1.2.4 has been removed. 
 
Amended protocol 02 (local for Israel): 15-Aug-2016 
This amended protocol (Amendment 02) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment 
Due to local regulatory approval in Israel for DNA material collection, and since there will be 
sufficient DNA samples collected in other countries for this study, it is the Sponsor’s proposal to 
not to collect DNA samples from patients enrolled in any Israeli site. 
Major changes specific to this global amendment include the following: 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 Study flow 
chart 
Section 9.6.1 Optional DNA 
stored sample,  
Section 10.1.1.2,  
Section 10.1.2.2,  
Section 10.1.2.4,  
Section 12.2 Informed 
consent 
Remove DNA sample collection for patients in 
Israel. 
Due to local regulatory approval in Israel for 
DNA material collection, and since there will 
be sufficient DNA samples collected in other 
countries for this study, it is the Sponsor’s 
proposal to not to collect DNA samples from 
patients enrolled in any Israeli site. 
 
Amended protocol 01 (local for Japan): 15-Nov-2016 
This amended protocol (Amendment 01) is considered to be substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment 
The Sponsor proposed to include Japanese Parkinson's disease patients carrying a GBA mutation 
(GBA-PD) in the planned global Phase 2 clinical study since, based on preliminary data, the 
probability of differences in PK and drug response between Japanese and non-Japanese 

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populations was expected to be low. In addition, the characterization of GZ/SAR402671 safety, 
tolerability, PK, and pharmacodynamics profile in Japanese GBA-PD patients may be more 
informative than in healthy Japanese subjects.  
It was not feasible for Japan to participate in Part 1 of the global Phase 2 clinical study as too few 
Japanese patients would be enrolled, given there were only 5 patients per dose cohort planned in 
Part 1 of the global study. Sanofi/Genzyme has considered it scientifically appropriate to include 
Japan in the multiple-country study with embedding Japanese dose escalation scheme instead of 
Phase 1 study in Japanese patients. 
Accordingly, the following modifications were proposed to the global study to optimize 
GZ/SAR402671 for characterization in Japanese GBA-PD patients since the number of diagnosed 
Japanese GBA-PD was very limited. The dose escalation phase (Part 1) in Japanese GBA-PD 
patients was conducted exactly as the dose escalation phase outside of Japan, except for a 3:1 
randomization ratio as opposed to a 4:1 randomization ratio outside of Japan. In major movement 
disorder centers, both within and outside of Japan, the majority of such centers had ≤10 patients 
with a known mutation that would be eligible for this. Other changes allow for clarifications of 
the original intent of the protocol. 
Major changes specific to this global amendment include the following: 
Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Clinical trial summary 
(study design); 
Section 6.1 Description of 
the study 
The study design was updated in order to 
describe the study duration, sample size and 
randomization ratio being used for Japanese 
GBA-PD patients in each part of this trial. 
It is not feasible for Japan to participate in 
Part 1 of the global Phase 2 clinical study as 
too few Japanese patients would be enrolled, 
given there are only 5 patients per dose cohort 
planned in Part 1 of the global study. 
Sanofi/Genzyme has considered it 
scientifically appropriate to include Japan in 
the multiple-country study with embedding 
Japanese dose escalation scheme instead of 
Phase 1 study in Japanese patients. 
Clinical trial summary 
(study population); 
Section 7.1 Inclusion 
criteria 
I03 was clarified in order to appropriately define 
the Japanese adult patient population age range. 
Throughout 
• 
Administrative change. 
• 
Minor editorial changes to punctuation, 
grammar, formatting, abbreviations, 
and syntax. 
• 
Sections and table footnote 
annotations renumbered. 
• 
In Part 2 Treatment Phase, site Visit 4 
at Week 0, Day 3 has been removed 
from Section 1.3.2 Part 2: Study 
schedule of assessments (periods 1 
and 2) flowchart for consistency (it was 
added to original protocol in error). 
Therefore, visit numbers throughout the 
protocol have been renumbered; 
Section 10.1.2.4 has been removed. 
Minor, therefore have not been summarized.