A Randomized, Double-Blind, Placebo-Controlled, 52-Week Phase II Study to Evaluate the Efficacy of Intravenous RO7046015/Prasinezumab (PRX002) in Participants With Early Parkinson's Disease With a 11-Year All-Participants-on-Treatment Extension
Phase: PHASE2
Conditions: Parkinson's Disease
Sponsor: Hoffmann-La Roche

 
Official Title: 
 
A Randomized, Double-Blind, Placebo-Controlled, 52-Week Phase II 
Study to Evaluate the Efficacy of Intravenous 
RO7046015/Prasinezumab (PRX002) in Participants With Early 
Parkinson's Disease With a 6-Year All-Participants-on-Treatment 
Extension (Pasadena) 
 
NCT Number: NCT03100149 
Document Date: Protocol Version 6: 20-March-2020 
 
 
 

FINAL PROTOCOL APPROVAL
CONFIDENTIAL
The information contained in this document, especially any unpublished data, is the property of 
F. Hoffmann-La Roche Ltd (or under its control) and therefore is provided to you in confidence as 
an Investigator, potential investigator, or consultant, for review by you, your staff, and an 
applicable Ethics Committee or Institutional Review Board. It is understood that this information 
will not be disclosed to others without written authorization from Roche except to the extent 
necessary to obtain informed consent from persons to whom the drug may be administered.
RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
Protocol BP39529, Version 6
PROTOCOL
TITLE:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, 52-WEEK PHASE II STUDY TO 
EVALUATE THE EFFICACY OF INTRAVENOUS 
RO7046015/PRASINEZUMAB (PRX002) IN 
PARTICIPANTS WITH EARLY PARKINSON’S 
DISEASE WITH A 6-YEAR ALL-
PARTICIPANTS-ON-TREATMENT 
EXTENSION (PASADENA)
PROTOCOL NUMBER:
BP39529
VERSION:
6
EUDRACT NUMBER:
2017-000087-15
IND NUMBER:
119602
TEST PRODUCT:
RO7046015
SPONSOR:
F. Hoffmann-La Roche Ltd
DATE FINAL:
Version 1: 01 March 2017
DATE AMENDED:
Version 2: 13 November 2017
Version 3: 27 June 2018
Version 4: 23 October 2019
Version 5: 6 March 2020
Version 6: See electronic date stamp below
 
20-Mar-2020 11:44:09
Title
Approver's Name
Company Signatory
Date and Time (UTC)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
2/Protocol BP39529, Version 6
PROTOCOL AMENDMENT ACCEPTANCE FORM
TITLE:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, 52-WEEK PHASE II STUDY TO 
EVALUATE THE EFFICACY OF INTRAVENOUS 
RO7046015/PRASINEZUMAB (PRX002) IN 
PARTICIPANTS WITH EARLY PARKINSON’S 
DISEASE WITH A 6-YEAR ALL-PARTICIPANTS-
ON-TREATMENT EXTENSION (PASADENA)
PROTOCOL NUMBER:
BP39529
VERSION NUMBER:
6
EUDRACT NUMBER:
2017-000087-15
IND NUMBER:
119602
TEST PRODUCT:
RO7046015
SPONSOR:
F. Hoffmann-La Roche Ltd
I agree to conduct the study in accordance with the current protocol.
Principal Investigator’s Name  (print)
Principal Investigator’s Signature
Date
Please keep the signed original form in your study files, and return a copy to your 
local Study Monitor.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
3/Protocol BP39529, Version 6
PROTOCOL AMENDMENT, VERSIONS 5 AND 6:
RATIONALE
Note: Protocol BP39529 Version 5 has not been submitted to health authorities and this 
rationale presents the changes included in both Version 5 and 6, respectively. 
Protocol BP39529 Version 5 has been amended to incorporate the following changes:

Addition of Part 3: A 5-year all participants on treatment extension. BP39529 has 
been amended to allow the patients who completed Part 2 and who completed the 
12-week treatment free follow up visit to enroll in Part 3. Part 3 is a 5-year all 
participants on treatment extension aiming to assess long-term safety and efficacy 
effects of RO7046015. Part 3 will start with the doses of RO7046015 tested in Part 2, 
patients will remain blinded to the dose they are receiving, and they were previously 
assigned too. When the dose used in the coming Phase III study will be known, 
patients will be switched to that dose. Details on this procedure and the schedule of 
activities have been added. (New sections: Section 3.1.1.3; Section 3.2.6; Appendix 
3; updated sections: Section 1.3.1, Section 2.2, Section 2.3, Section 3.1.1, Figure 1, 
Section 3.1.1.4, Section 3.1.3, Section 3.2, Section 3.3.4, Section 4.2.2, Section 
4.4.4, Section 6.6, Section 6.9; minor updates to other sections throughout protocol 
to include reference to Part 3).

Section 1 (Background and Rationale) has been updated to include details on the 
most recent clinical study data. As such, Section 1.2 has been updated to include 
details on an additional Phase I study that has been performed. Section 1.3 has 
been updated to reflect the most recent safety data as presented in the latest 
Investigator Brochure.

Section 2.3 and Section 3.3.4 have been updated to align and clarify the study 
objectives with the listed outcome measures and vice versa. 
Protocol BP39529 Version 6 has been amended to incorporate the following changes:

Two additional MRI sequences (iron and neuromelanin-sensitive imaging) have 
been added to the MRI battery. Sections 2.3, Section 3.2.7.2, Section 3.3.4, Section 
4.6.1.9 and Appendix 2 & 3 have been updated to reflect these changes.
Additional minor corrections and changes have been made to improve clarity and 
consistency. Substantial new information (for Version 5 and Version 6) appears in book 
antiqua italics. This amendment represents cumulative changes to the original protocol.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
4/Protocol BP39529, Version 6
TABLE OF CONTENTS
PROTOCOL AMENDMENT ACCEPTANCE FORM ............................................ 2
PROTOCOL SYNOPSIS .................................................................................... 11
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS............................. 24
1.
BACKGROUND AND RATIONALE ............................................................ 28
1.1
Background on Disease......................................................... 28
1.2
Background on RO7046015 .................................................. 29
1.2.1
Previous Non-Clinical Studies ............................................... 29
1.2.2
Previous Clinical Studies ....................................................... 30
1.3
Study Rationale and Benefit–Risk Assessment..................... 32
1.3.1
Study Rationale ..................................................................... 32
1.3.2
Benefit-Risk Assessment....................................................... 33
2.
OBJECTIVES.............................................................................................. 35
2.1
Primary Objective .................................................................. 35
2.2
Secondary Objectives............................................................ 35
2.3
Exploratory Objectives........................................................... 35
3.
STUDY DESIGN......................................................................................... 37
3.1
Description of Study .............................................................. 37
3.1.1
Overview of Study Design ..................................................... 37
3.1.1.1
Part 1..................................................................................... 37
3.1.1.2
Part 2..................................................................................... 38
3.1.1.3
Part 3..................................................................................... 39
3.1.1.4
Duration of Study................................................................... 41
3.1.2
Independent Data Monitoring Committee .............................. 42
3.1.2.1
Review of Safety Data by the Independent Data 
Monitoring Committee............................................................ 42
3.1.2.2
Review of Efficacy Data by the Independent Data 
Monitoring Committee............................................................ 42
3.1.3
End of Study.......................................................................... 43
3.2
Rationale for Study Design.................................................... 43
3.2.1
Rationale for Study Population .............................................. 43
3.2.2
Rationale for Control Group................................................... 45

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3.2.3
Rationale for Dosage Selection ............................................. 45
3.2.4
Rationale for Duration of Treatment ...................................... 47
3.2.5
Rationale for One-Year Extension (Part 2) ............................ 47
3.2.6
Rationale for Five-Year Extension (Part 3) ............................ 48
3.2.7
Rationale for Biomarkers and Digital 
Assessments ......................................................................... 48
3.2.7.1
DaT-SPECT........................................................................... 48
3.2.7.2
Magnetic Resonance Imaging ............................................... 48
3.2.7.3
Digital Biomarkers ................................................................. 50
3.2.7.4
Clinical Genotyping................................................................ 50
3.2.7.5
Cerebrospinal Fluid Biomarkers ............................................ 50
3.2.7.6
Skin Biopsy and Collection of Screen Failure 
Data and Samples................................................................. 50
3.3
Outcome Measures ............................................................... 51
3.3.1
Safety Outcome Measures .................................................... 51
3.3.2
Pharmacokinetic Outcome Measures.................................... 51
3.3.3
Efficacy Outcome Measures.................................................. 51
3.3.4
Exploratory Outcome Measures ............................................ 52
4.
MATERIALS AND METHODS .................................................................... 53
4.1
Center.................................................................................... 53
4.2
Study Population ................................................................... 53
4.2.1
Recruitment Procedures........................................................ 53
4.2.2
Inclusion Criteria.................................................................... 53
4.2.3
Exclusion Criteria................................................................... 55
4.3
Method of Treatment Assignment and Blinding..................... 58
4.4
Study Treatment.................................................................... 60
4.4.1
Formulation, Packaging, and Handling of 
RO7046015 ........................................................................... 60
4.4.2
Dosage, Administration and Compliance............................... 61
4.4.3
Investigational Medicinal Product Accountability ................... 63
4.4.4
Post-trial Access to RO7046015............................................ 64
4.5
Concomitant Therapy ............................................................ 64
4.5.1
Permitted Therapy................................................................. 65
4.5.1.1
For Participants on MAO-B Inhibitor Therapy........................ 65

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4.5.1.2
Other Permitted Therapy ....................................................... 65
4.5.2
Prohibited Therapy ................................................................ 66
4.5.2.1
MAO-B Inhibitor Therapy....................................................... 66
4.5.2.2
Other Prohibited Therapy ...................................................... 66
4.5.3
Other Symptomatic PD Therapy............................................ 67
4.5.4
Dietary Restrictions ............................................................... 67
4.6
Study Assessments ............................................................... 67
4.6.1
Description of Study Assessments ........................................ 67
4.6.1.1
Medical History and Demographic Data ................................ 67
4.6.1.2
Physical and Neurological Examinations............................... 68
4.6.1.3
Vital Signs.............................................................................. 68
4.6.1.4
Electrocardiograms................................................................ 69
4.6.1.5
Laboratory Assessments ....................................................... 70
4.6.1.6
Pharmacokinetic Assessments.............................................. 71
4.6.1.7
Immunogenicity Assessments ............................................... 71
4.6.1.8
Biomarker Samples ............................................................... 72
4.6.1.9
Disease-Specific Assessments.............................................. 73
4.6.1.10
Participant-Reported Outcomes ............................................ 79
4.6.1.11
Patient Engagement Application............................................ 81
4.6.1.12
Samples for Research Biosample Repository ....................... 82
4.6.2
Timing of Study Assessments ............................................... 84
4.6.2.1
Screening and Pretreatment Assessments............................ 85
4.6.2.2
Assessments during Treatment............................................. 85
4.6.2.3
Assessments Prior to Start of 
Dopaminergic/Symptomatic PD Treatment............................ 86
4.6.2.4
Assessments at Study Completion/Early 
Termination Visit.................................................................... 86
4.6.2.5
Assessments at Unscheduled Visits...................................... 86
4.7
Participant, Study, and Site Discontinuation.......................... 86
4.7.1
Study and Site Discontinuation.............................................. 86
4.7.2
Participant Discontinuation .................................................... 87
4.7.2.1
Discontinuation from Study Treatment .................................. 87
4.7.2.2
Withdrawal from Study........................................................... 87

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5.
ASSESSMENT OF SAFETY....................................................................... 88
5.1
Safety Parameters and Definitions ........................................ 88
5.1.1
Adverse Events ..................................................................... 88
5.1.2
Serious Adverse Events (Immediately Reportable 
to the Sponsor)...................................................................... 89
5.1.3
Non-Serious Adverse Events of Special Interest 
(Immediately Reportable to the Sponsor) .............................. 89
5.1.4
Selected Adverse Events....................................................... 90
5.2
Safety Plan ............................................................................ 90
5.2.1
Management of Specific Adverse Events .............................. 90
5.3
Methods and Timing for Capturing and 
Assessing Safety Parameters................................................ 95
5.3.1
Adverse Event Reporting Period ........................................... 95
5.3.2
Eliciting Adverse Event Information....................................... 96
5.3.3
Assessment of Severity of Adverse Events ........................... 96
5.3.4
Assessment of Causality of Adverse Events ......................... 97
5.3.5
Procedures for Recording Adverse Events............................ 98
5.3.5.1
Diagnosis versus Signs and Symptoms................................. 98
5.3.5.2
Adverse Events Occurring Secondary to Other 
Events.................................................................................... 98
5.3.5.3
Persistent or Recurrent Adverse Events................................ 99
5.3.5.4
Abnormal Laboratory Values ................................................. 99
5.3.5.5
Abnormal Vital Sign Values ................................................. 100
5.3.5.6
Abnormal Liver Function Tests............................................ 100
5.3.5.7
Deaths ................................................................................. 101
5.3.5.8
Preexisting Medical Conditions............................................ 101
5.3.5.9
Lack of Efficacy or Worsening of Parkinson’s 
Disease................................................................................ 101
5.3.5.10
Hospitalization or Prolonged Hospitalization........................ 101
5.3.5.11
Overdoses and Medication Errors ....................................... 102
5.3.5.12
Patient-Reported Outcome Data ......................................... 102
5.4
Immediate Reporting Requirements from 
Investigator to Sponsor........................................................ 102
5.4.1
Emergency Medical Contacts.............................................. 103

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5.4.2
Reporting Requirements for Serious Adverse 
Events and Non-Serious Adverse Events of 
Special Interest.................................................................... 103
5.4.2.1
Events That Occur prior to Study Drug Initiation.................. 103
5.4.2.2
Events That Occur after Study Drug Initiation...................... 103
5.4.3
Reporting Requirements for Pregnancies............................ 104
5.4.3.1
Pregnancies in Female Participants .................................... 104
5.4.3.2
Pregnancies in Female Partners of Male 
Participants.......................................................................... 104
5.4.3.3
Abortions ............................................................................. 104
5.4.3.4
Congenital Anomalies/Birth Defects .................................... 105
5.5
Follow-Up of participants after Adverse Events................... 105
5.5.1
Investigator Follow-Up......................................................... 105
5.5.2
Sponsor Follow-Up .............................................................. 105
5.6
Post-Study Adverse Events................................................. 105
5.7
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees............................................................... 106
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN..................... 106
6.1
Determination of Sample Size ............................................. 106
6.2
Summaries of Conduct of Study.......................................... 108
6.3
Analysis Populations ........................................................... 108
6.3.1
Safety Analysis Population .................................................. 108
6.3.2
Efficacy Analysis Populations.............................................. 108
6.3.3
Immunogenicity Analysis Population ................................... 108
6.3.4
Pharmacokinetic Analysis Population.................................. 108
6.4
Summaries of Treatment Group Comparability ................... 109
6.5
Safety Analyses................................................................... 109
6.5.1
Adverse Events ................................................................... 109
6.5.2
Clinical Laboratory Test Results.......................................... 109
6.5.2.1
Standard Reference Ranges and Transformation 
of Data................................................................................. 110
6.5.2.2
Definition of Laboratory Abnormalities................................. 110
6.5.3
Vital Signs............................................................................ 110

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6.5.4
ECG Data Analysis.............................................................. 110
6.5.5
Concomitant Medications .................................................... 111
6.6
Efficacy Analyses ................................................................ 111
6.6.1
Primary Efficacy Endpoint.................................................... 112
6.6.2
Secondary Efficacy Endpoints............................................. 113
6.7
Pharmacokinetic and Pharmacodynamic 
Analyses.............................................................................. 114
6.8
Exploratory Analyses........................................................... 115
6.9
Efficacy Interim Analyses..................................................... 116
7.
DATA COLLECTION AND MANAGEMENT ............................................. 116
7.1
Data Quality Assurance....................................................... 116
7.2
Electronic Case Report Forms............................................. 117
7.3
Digital Biomarker Data......................................................... 117
7.4
Source Data Documentation................................................ 117
7.5
Use of Computerized Systems ............................................ 118
7.6
Retention of Records........................................................... 118
8.
ETHICAL CONSIDERATIONS.................................................................. 119
8.1
Compliance with Laws and Regulations .............................. 119
8.2
Informed Consent................................................................ 119
8.3
Institutional Review Board or Ethics Committee.................. 120
8.4
Confidentiality...................................................................... 120
8.5
Financial Disclosure ............................................................ 121
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ................................................................................... 121
9.1
Study Documentation .......................................................... 121
9.2
Site Inspections ................................................................... 122
9.3
Administrative Structure....................................................... 122
9.4
Publication of Data and Protection of Trade 
Secrets ................................................................................ 122
9.5
Protocol Amendments ......................................................... 123
10. REFERENCES ......................................................................................... 124

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LIST OF TABLES
Table 1
Guidelines for Managing IRRs .................................................... 91
Table 2
Infusion-Related Reaction Grading............................................. 95
Table 3
Adverse Event Severity Grading Scale ....................................... 97
Table 4
Assumptions Used for Simulations ........................................... 107
LIST OF FIGURES
Figure 1
Study Design............................................................................... 41
Figure 2
Evaluation and Reporting of Infusion Related Reactions (IRR)....93
LIST OF APPENDICES
Appendix 1
Schedule of Assessments (Part 1)............................................ 130
Appendix 2
Schedule of Assessments (Part 2)............................................ 134
Appendix 3
Schedule of Assessments (Part 3)............................................ 138
Appendix 4
Recommended Sequence of Study Assessments .................... 160
Appendix 5
Patient Engagement Application............................................... 165

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
11/Protocol BP39529, Version 6
PROTOCOL SYNOPSIS
TITLE:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 52-
WEEK PHASE II STUDY TO EVALUATE THE EFFICACY OF 
INTRAVENOUS RO7046015/PRASINEZUMAB (PRX002) IN 
PARTICIPANTS WITH EARLY PARKINSON’S DISEASE WITH A 
6-YEAR ALL-PARTICIPANTS-ON-TREATMENT EXTENSION
(PASADENA)
PROTOCOL NUMBER:
BP39529
VERSION:
6
EUDRACT NUMBER:
2017-000087-15
IND NUMBER:
119602
TEST PRODUCT:
RO7046015
PHASE:
II
INDICATION:
Parkinson’s disease
SPONSOR:
F. Hoffmann-La Roche Ltd
OBJECTIVES
Primary Objectives
The primary objective of this study is:

To evaluate the efficacy of RO7046015 versus placebo at Week 52 in participants with early 
Parkinson’s disease (PD) (Hoehn & Yahr [H&Y] Stages I-II) who are untreated or treated 
with monoamine oxidase B (MAO-B) inhibitors since baseline, as measured by change from 
baseline on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale
(MDS-UPDRS) Total Score (sum of Parts I, II and III).
Secondary Objectives
The secondary objectives of this study are:

To evaluate the effects of RO7046015 versus placebo at Week 52, in participants with early 
PD (H&Y Stages I-II) who are untreated or treated with MAO-B inhibitors since baseline, on 
the following:
–
MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total and Part III subscores 
–
Dopamine transporter imaging with single photon emission computed tomography 
(DaT-SPECT) in the ipsilateral (to the clinically dominant side) putamen.
–
Montreal Cognition Assessment (MoCA) total score 
–
Clinical Global Impression of Improvement (CGI-I)
–
Patient Global Impression of Change (PGIC)
–
Schwab and England Activity of Daily Living (SE-ADL) score 
–
Time to worsening in motor or non-motor symptoms 
–
Time to start of dopaminergic PD treatment (levodopa or dopamine agonists)
–
Safety and tolerability of RO7046015.

To evaluate the safety and tolerability of treatment with RO7046015 for up to 104 weeks

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
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(Part 2) and up to Part 3 Week 260, with or without concomitant dopaminergic treatment.

To evaluate the immunogenicity of RO7046015.

To describe the pharmacokinetics (PK) of RO7046015 using population PK modelling.
Exploratory Objectives
The exploratory objectives of this study are:

To compare consistency and accuracy in MDS-UPDRS Part III total, Part III subscores 
centrally rated by video-tapes vs locally rated by the site (in Part 1 and Part 2 only)

Time to worsening in motor or non-motor symptoms or starting dopaminergic PD treatment 
(levodopa or dopamine agonist) 

To evaluate the effect of RO7046015 versus placebo over 52 weeks, on change from 
baseline in:
–
Modified Hoehn and Yahr, Hospital Anxiety and Depression Scale (HADS), Patient 
Assessment of Constipation Symptoms (PAC-SYM), Scales for outcomes in Parkinson’s 
disease autonomic dysfunction (SCOPA-AUT), Parkinson’s Disease Sleep Scale 
Revised Version 2 (PDSS-2), 39-item Parkinson’s Disease Questionnaire (PDQ-39), 
European Quality of Life Questionnaire 5-level version [EQ-5D-5L] and Smartphone and 
wrist-worn wearable assessments.
–
Serum, plasma, cerebrospinal fluid (CSF), skin, and imaging biomarkers related to 
Parkinson’s disease.

To evaluate clinical and biomarker outcomes (as outlined above) over a period of up to 
104 weeks including data from the one-year extension (Part 2) (all-participants-on-treatment,
blinded to dose) with or without concomitant dopaminergic treatment.

To evaluate clinical and biomarker outcomes (as outlined above) in the five-year extension 
(Part 3) (all-participants-on-treatment, blinded to dose until Phase III study dose has been 
identified) with or without concomitant dopaminergic treatment.

To evaluate the dose-exposure-response (pharmacokinetic/pharmacodynamic [PK/PD]) 
relationship for MDS-UPDRS, DaT-SPECT and other functional, biomarker and safety 
parameters.

To evaluate an immunohistochemical assay for -synuclein pathology in peripheral nerves 
(skin biopsy samples from randomized participants and DaT-SPECT screen failures).

To assess time to start or change of co-medication for non-motor symptoms that may be 
related to PD (cognition, constipation, depression, anxiety, excessive daytime sleep, 
nocturnal sleep, urogenital symptoms/sexual dysfunction).

To assess start or change of co-medication for non-motor symptoms that may be related to 
imaging biomarkers (DAT Scan and ASL).

To assess Parkinson-related effects on the loss of autonomic tone as measured by heart rate 
variability. 

To evaluate motor progression as assessed by a composite score of MDS-UPDRS Part II 
(patient reported motor experiences of daily living) and MDS-UPDRS Part III (clinician 
rated motor signs of PD) sub-items 

To assess motor complications as assessed by MDS-UPDRS Part IV at Week 52, at Week 
104 and Part 3 Week 260 in participants who started dopaminergic treatment (levodopa or 
dopamine agonist).
STUDY DESIGN
Description of Study
This is a multicenter, Phase II study to evaluate the effect of IV administration of RO7046015 in 
participants with early stage (H&Y Stages I-II) PD. Participants will be eligible if they have 
idiopathic PD with bradykinesia plus one of the other cardinal signs of PD (resting tremor, 
rigidity) being present, without any other known or suspected cause of PD (adapted from the 

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MDS Clinical Diagnostic Criteria for Parkinson’s Disease) and are either untreated or treated 
only with MAO-B inhibitor. 
The study will consist of three parts: a 52-week, double-blind, placebo-controlled treatment 
period (Part 1) after which eligible participants will continue into an all-participants-on-treatment 
(RO7046015) blinded to dose extension for an additional 52 weeks (Part 2). Participants who 
complete Part 2 (including the 12-week treatment free follow up visit assessing long term 
safety and efficacy of RO7046015) will be offered participation in Part 3 (all-participants-on-
treatment (RO7046015) blinded to dose until Phase III study dose has been identified) for an 
additional 260 weeks.
Part 1
During Part 1 of the study, participants will receive IV infusions of RO7046015 or placebo once 
every four weeks (Q4W) over a period of 52 weeks.
Participants will be randomized with a 1:1:1 allocation ratio to placebo, or one of the two active 
treatment doses: high dose (4500 mg for body weight 65 kg; 3500 mg for body weight 65 kg), 
low dose (1500 mg; for all body weights).
Randomization will be stratified by sex, age group and existence or lack of prior background 
therapy (untreated or treated with stable MAO-B inhibitor therapy at baseline).
To enhance the tolerability of RO7046015 infusions, a dose titration regimen that may reduce the 
risk of IRRs will be implemented for the high dose, as follows: 2000 mg will be infused on Day 1 
followed by an up-titration to the full dose of 4500 mg (65 kg body weight) or 3500 mg (65 kg 
body weight) on the second infusion (Day 28) during Part 1.
Participants are expected not to start dopaminergic therapy (levodopa or dopamine agonist) or 
other symptomatic PD therapy during the 52-week double-blind placebo-controlled period. Some 
participants may experience worsening of their symptoms to an extent that they are unable to 
tolerate in their personal or professional life. These participants may start dopaminergic or 
symptomatic PD treatment according to local guidelines after completing the assessments at the 
“prior to start of dopaminergic or symptomatic PD treatment” visit according to the schedule of 
assessments and the Investigator must record the reasons and the type and dose of 
dopaminergic or symptomatic PD treatment started. 
For the main analysis of the primary endpoint and other efficacy endpoints that are sensitive to 
dopaminergic treatment (such as MDS-UPDRS part III, PGIC, CGI-I), only data up to the last 
measurement before start of symptomatic PD treatment will be used. Data after start of 
symptomatic PD treatment will be included in safety, sensitivity, exploratory and biomarker 
evaluations as appropriate.
All participants, including those that have started symptomatic PD treatment, will be eligible to 
participate in Part 2 if they have completed Part 1 with the predefined minimum of infusions and 
assessments as defined below.
Part 2
Part 2 is a one-year all-participants-on-treatment, blinded to dose extension.
Participants must meet the following criteria to enter Part 2: DaT-SPECT and magnetic 
resonance imaging (MRI) scans completed at Screening and Week 52 and received at least 
10 doses of study treatment (RO7046015 or Placebo) during Part 1 of the study. Participants may 
initiate or change symptomatic PD treatment (including dopaminergic treatment) as per standard 
of care (SOC) during Part 2.
For Part 2, participants who complete the initial placebo-controlled part and fulfil the criteria 
mentioned above will switch into the extension:

Participants initially randomized to placebo will be re-randomized to one of the two active 
doses using a 1:1 allocation ratio. 
Randomization will be stratified by: dopaminergic therapy since start of the study (Yes 
versus No), age group (60 versus 60) and prior background therapy with MAO-B inhibitor 
(Yes versus No). Note that for age group and prior background therapy with MAO-B inhibitor 
the values collected for Part 1 will be used. 

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Participants receiving placebo during Part 1 and randomized to the high dose at the start of 
Part 2 (extension) will receive 2000 mg IV on Week 56 followed by an up-titration to the full 
dose of 4500 mg (65 kg body weight) or 3500 mg (65 kg body weight) on the second 
infusion (Week 60).

Participants initially randomized to the active dose will remain on their dose.
Part 3
Part 3 is a 5-year extension in which all participants will be on treatment. Participants will be 
blinded to dose until the Phase III study dose is identified (Note: this dose will not exceed the 
high dose tested in the present BP39529 study). Once the Phase III study dose is identified, 
participants will be switched to that dose (if applicable). 
Participants must meet the following criteria to enter Part 3: 

Having completed Part 2 (i.e., completed Week 104 visit) as well as the 12-week treatment 
free follow up visit. Participants may initiate or change symptomatic PD treatment 
(including dopaminergic treatment) as per standard of care during Part 3.

Not having received another investigational medication during the treatment free period 
(i.e., between Week 104 visit and Part 3 Week 1 visit).

Participation in Part 3 not deemed inappropriate by the Investigator (e.g., patient with 
serious medical condition or other concerns that preclude their safe participation in Part 3 
or their ability to comply with the required procedures should not be enrolled).
NUMBER OF PARTICIPANTS
Approximately 300 participants are planned to be enrolled which could be increased to a 
maximum of 360 depending on the outcome of the independent Data Monitoring Committee 
(iDMC) safety review. The sample size may also be adjusted to up to 360 participants if 
assumptions (e.g., drop-out rate) used for sample size calculation need to be adapted.
TARGET POPULATION
Men and women, aged 40 to 80 years inclusive, with early PD (H&Y Stage I or II), who were 
recently (2 years) diagnosed, and either de novo (untreated) or treated with a MAO-B inhibitor.
Only early stage PD patients with a clinical condition not requiring dopaminergic PD medication 
at baseline and not expected to require dopaminergic treatment within 12 months from baseline 
will be eligible to participate in the study. Patients with a history of stable parkinsonian symptoms 
who are on a stable dose of MAO-B inhibitor (rasagiline or selegiline) for at least 90 days prior to 
baseline may also be included. 
INCLUSION/EXCLUSION CRITERIA
Inclusion Criteria:
Participants must meet the following criteria for study entry:
1.
Idiopathic PD with bradykinesia plus one of the other cardinal signs of PD (resting tremor, 
rigidity) being present, without any other known or suspected cause of PD untreated or 
treated with MAO-B inhibitor.
2.
Male or female, 40 to 80 years of age, body weight range of 45 kg/99 lbs to 110 kg/242 lbs 
and a body mass index (BMI) of 18 to 34 kg/m2.
3.
A diagnosis of PD for 2 years or less at screening.
4.
H&Y Stage I or II.
5.
A screening brain DaT-SPECT consistent with PD (central reading).
6.
Clinical status does not require dopaminergic PD medication and is not expected to require 
dopaminergic treatment within 52 weeks from baseline.
7.
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at least 90 days prior to baseline and not expected to change within 52 weeks. 
8.
Able and willing to provide written informed consent and to comply with the study protocol 
according to ICH and local regulations.
9.
For women of childbearing potential: use of highly effective contraceptive methods (that result 
in a failure rate of 1% per year) during the treatment period and for at least 30 days (or 
longer if required by local regulations) after the last dose of study drug. 
A woman is considered to be of childbearing potential if she is post-menarcheal, has not 
reached a post-menopausal state (12 continuous months of amenorrhea with no 
identified cause other than menopause), and has not undergone surgical sterilization 
(removal of ovaries and/or uterus).
Examples of highly effective contraceptive methods (with a failure rate of 1% per year) 
include bilateral tubal ligation, vasectomized partner, established, proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper 
intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are 
not acceptable methods of contraception.
10. For men: use of contraceptive measures as defined below:
With female partners of childbearing potential or pregnant female partners, men must use 
a condom during the treatment period and for at least 30 days (or longer if required by 
local regulations) after the last dose of study drug to avoid exposing the embryo. Men 
must refrain from donating sperm during this same period. The female partners should 
use a contraception method with a failure rate of 1% per year during the treatment 
period and for at least 30 days (or longer if required by local regulations) after the last 
dose of study drug.
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are 
not acceptable methods of contraception.
Exclusion Criteria:
Participants who meet any of the following criteria will be excluded from study entry:
Current or Past Medical History
1.
Medical history indicating a Parkinson syndrome other than idiopathic PD, including but not 
limited to, progressive supranuclear gaze palsy, multiple system atrophy, drug-induced 
parkinsonism, essential tremor, primary dystonia.
2.
Known carriers of certain familial PD genes (Parkin, PINK1, DJ1). Note: GBA, synuclein, 
LRRK2 mutation carriers are allowed.
3.
History of PD-related freezing episodes or falls.
4.
A diagnosis of a significant CNS disease other than Parkinson’s disease (including but not 
limited to Huntington’s disease, normal pressure hydrocephalus, cerebrovascular disease 
including stroke, fronto-temporal dementia, Alzheimer’s disease); history of repeated head 
injury; history of epilepsy or seizure disorder other than febrile seizures as a child.
5.
Mini Mental State Examination (MMSE) 25.
6.
Reside in a nursing home or assisted care facility.
7.
History of or screening brain MRI scan indicative of clinically significant abnormality including, 
but not limited to, prior hemorrhage or infarct 1 cm3, 3 lacunar infarcts.
8.
Concomitant disease or condition within six months of screening, or as specified below, that 
could interfere with, or treatment of which might interfere with, the conduct of the study, or 
that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in 
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study restrictions, or with the ability to interpret safety data, including, but not limited to:
a.
Autoimmune disease (however, well controlled conditions such as, but not limited to, 
quiescent rheumatoid arthritis [RAS], controlled type I diabetes, or mild-to-moderate 
psoriasis not requiring systemic medications may be acceptable after discussion with 
Sponsor/Medical monitors).
b.
A history of cancer within 5 years of baseline with the exception of fully excised 
non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at 
least 6 months.
c.
Any active infectious disease at baseline.
d.
Current or history of, alcohol or drug abuse or other dependence (except nicotine 
dependence) within two years before screening.
e.
Any febrile illness within one week prior to first dose administration.
f.
Any current psychiatric diagnosis according to Diagnostic and Statistical Manual of 
Mental Disorders fifth edition (DSM-5), International Statistical Classification of Diseases 
and Related Health Problems 10th Revision (ICD-10) or equivalent, that may interfere 
with the participant’s ability to perform the study and all assessments (e.g., major 
depression, mental retardation, schizophrenia, bipolar disorder, etc.). Note: Mild 
depression, depressive mood or mild anxiety arising in the context of PD, are not 
exclusionary.
9.
The following cardiovascular conditions:
a.
Myocardial infarction within 12 months of baseline.
b.
Known history or documentation of uncontrolled hypotension or bradycardia on more than 
one occasion within 3 months prior to baseline.
c.
Known history or documentation of uncontrolled hypertension on more than one occasion 
within three months prior to baseline.
d.
Resting pulse rate (PR) greater than 100 or less than 45 bpm.
e.
Clinically significant cardiovascular disease including any of the following: unstable 
angina, decompensated congestive heart failure, clinically significant arrhythmias or 
symptomatic orthostatic hypotension.
f.
A corrected QT (QTcF) interval measurement 450 ms for males or 470 ms for 
females at screening, or a family history of long QT syndrome.
g.
Intermittent second or third degree atrioventricular (AV) heart block or AV dissociation is 
excluded (asymptomatic first degree AV block may be included).
10. Clinically significant abnormalities in laboratory test results at the Screening visit, including 
hepatic and renal panels, complete blood count, chemistry panel and urinalysis, including:
a. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 
times the upper limit of normal (ULN).
b. Serum creatinine 1.5 times the ULN.
c. Hematocrit (Hct) less than 35% for males and less than 32% for females, or absolute 
neutrophil cell count of 1500/µL (with the exception of a documented history of a chronic 
benign neutropenia), or platelet cell count of 120,000/µL; international normalized ratio 
(INR) 1.4 (in patients not on anticoagulants) or other coagulopathy.
d. A clinically significant abnormal thyroid-stimulating hormone (TSH) test.
e. A positive urine drug screen for a drug of abuse.

For participants treated with selegiline, the amphetamine drug abuse test should be 
based on the results from a urine assay by liquid chromatography-mass spectrometry 
which is able to differentiate “false positive methamphetamine” from “true positive 
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
For participants treated with benzodiazepines: a positive urine drug screen for 
benzodiazepines is allowed, provided that the prescription has been stable for 90 
days prior to baseline (please also refer to exclusion criterion 15).
f.
Positive result for acute or chronic infectious hepatitis B (HBV; [i.e., HBsAg positive test]), 
for hepatitis C (HCV), or HIV 1 or 2. Successfully treated HCV patients (undetectable HCV 
RNA) are eligible for enrollment. Participants who are immune due to HBV natural 
infection or HBV vaccination are eligible.
g. For women of childbearing potential, a positive urine or blood pregnancy test.
11.Lactating women.
Medications and treatments
12. Prior treatment with dopaminergic medication (e.g., levodopa or a dopaminergic agonist) with 
no clinical treatment response or a clinical treatment response inconsistent with PD (e.g., 
absence of observable response to a sufficiently high dose of levodopa [i.e., 600 mg/day]).
13. Use of any of the following: catechol-O-methyl transferase (COMT) inhibitors (entacapone, 
tolcapone), amantadine or anticholinergics, or dopaminergic medication (levodopa and both 
ergot and non-ergot [pramipexole, ropinirole, rotigotine] dopamine agonists) for more than a 
total of 60 days or within 60 days of baseline.
14. Anti-epileptic medication for non-seizure-related treatment which has not remained stable for 
at least 60 days prior to baseline.
15. Anti-depressant or anxiolytic use that has not remained stable for at least 90 days prior to 
baseline. The use of fluoxetine and fluvoxamine is not permitted. For patients treated with an 
MAO-B inhibitor and an antidepressant (except fluoxetine and fluvoxamine), a 6-month period 
of stable and tolerated dosing before baseline is required.
16. Use of any of the following within 90 days prior to baseline; antipsychotics (including 
clozapine and olanzapine), metoclopramide, alpha methyldopa, flunarizine, amoxapine, 
amphetamine derivatives, reserpine, bupropion, buspirone, cocaine, mazindol, 
methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, and 
modafinil. 
17. Participated in an investigational drug, device, surgical or stem cell study in PD.
18. Any prior treatment with an investigational PD-related vaccine (including active immunization 
or passive immunotherapy with monoclonal antibodies).
19. Prior participation in any RO7046015 or PRX002 study.
20. Receipt of any non-PD investigational product or device, or participation in a non-PD drug 
research study within a period of 30 days (or 5 half-lives of the drug, whichever is longer) 
before baseline.
21. Receipt of any monoclonal antibody or investigational immunomodulator within 180 days (or 5 
half-lives, whichever is longer) before baseline (e.g., monoclonal antibodies, intravenous 
immunoglobulin [IVIG], interleukin 2 [IL-2], interleukin 12 [IL-12], interferon or 
immunosuppressive drugs).
22. Immunomodulating drugs within 30 days prior to baseline.
23. Allergy to any of the components of RO7046015 such as citrate, trehalose and polysorbate 
(Tween) 20 or a known hypersensitivity or an infusion-related reaction (IRR) to the 
administration of any other monoclonal antibody.
Procedural
24. Any contraindications to obtaining a brain MRI (e.g., claustrophobia unresponsive to 
reassurance or low dose of an anxiolytic agent, tooth implants) and any contraindications to 
obtain a DaT-SPECT (i.e., known hypersensitivity to the active substance or to any of the 
excipients). Patients with a hypersensitivity to iodine may receive an alternative thyroid 
blocking agent (e.g., potassium perchlorate or sodium perchlorate). 
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only be performed if the participant does not have any contraindication to undergoing an LP 
including, but not limited to: INR 1.4 or other coagulopathy, platelet cell count 
of 120,000/L, infection at the desired LP site, taking anti-coagulant medication within 
90 days of baseline (Note: low dose aspirin (acetylsalicylic acid [ASA] is permitted), severe 
degenerative arthritis of the lumbar spine, suspected non-communicating hydrocephalus or 
intracranial mass, prior history of spinal mass or trauma is/are identified. Participants failing to 
meet these criteria can still participate in the study and all other study assessments (with the 
exception of LP) as appropriate. Participants could be excluded from the study if the CSF has 
more than 5 WBCs/mm3 (according to local laboratory assessment). This should be 
discussed with the Medical Monitor (e.g., if there is evidence that the spinal tap was 
traumatic, the participant may still be considered for study eligibility).
26. For skin biopsy at the cervical paravertebral region:
Condition that either precludes the safe performance of the skin punch biopsy or may 
interfere with obtaining evaluable skin tissue biopsies, including any previous or active 
significant dermatological disease (e.g., previous biopsy with any of the following findings: 
inflammatory disease, scar tissue, psoriasis, keloid formation, skin cancer).
Participants failing to meet these criteria can still participate in the study and all other study 
assessments (with the exception of skin biopsy) as appropriate.
27. Donation of blood over 500 mL within three months prior to screening.
LENGTH OF STUDY
The study for each patient will be divided as follows:

Screening: Up to 8 weeks

Treatment period: 364 weeks (52 weeks in Part 1, 52 weeks in Part 2 and 260 weeks in Part 
3)

Safety Follow-up: up to 12 weeks after cessation of double-blind treatment (regardless of 
whether cessation of treatment occurs at the end of or during Part 1 or Part 2).     

Part 3 Safety Follow-up: 12 weeks after cessation of treatment (regardless of whether 
cessation of treatment occurs at the end of or during Part 3).
END OF STUDY
The end of the study is defined as the date when the last participant last observation (LPLO) 
occurs at the follow-up visit. LPLO is expected to occur approximately 388 weeks after the last 
participant is enrolled, or earlier in the case that the study is discontinued following any of the 
planned interim analyses.
OUTCOME MEASURES
SAFETY OUTCOME MEASURES
The safety outcome measures for this study are as follows:

Changes in safety laboratory tests (hematology, chemistry and coagulation) from baseline 
over time.

Incidence of treatment-emergent abnormal laboratory values and abnormal laboratory values 
reported as adverse events (AEs).

Incidence and severity of AEs.

Incidence of anti-drug antibodies (ADAs)

Changes in electrocardiogram (ECG) assessments from baseline over time; incidence of 
abnormal ECG assessments.

Change in blood pressure (BP [systolic and diastolic], heart rate, and orthostatic 
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diastolic], heart rate, and orthostatic changes).

Incidence of exacerbation of motor and psychiatric side-effects (including C-SSRS).

Incidence of MRI abnormalities.
PHARMACOKINETIC OUTCOME MEASURES
The PK outcome measures for this study are as follows:

Population and individual primary PK parameter estimations (e.g., clearance and volume of 
distribution) and the influence of various covariates on these parameters.

Secondary PK parameters (e.g., AUC, Ctrough) derived from the individual post-hoc 
predictions.
EFFICACY OUTCOME MEASURES
The primary efficacy outcome measure for this study is as follows:

Change in total MDS-UPDRS score (sum of Parts I, II and III) from baseline at Week 52.
The secondary efficacy outcome measures for this study (after 52 weeks of treatment with 
RO7046015 or placebo) are as follows:

Change from baseline in MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total 
and Part III subscores

Change from baseline in DaT-SPECT in ipsilateral (to the clinically dominant side) putamen 
binding ratio values.

Change from baseline in MoCA total score 

Change from baseline in Clinical Global Impression (CGI-I).

Change from baseline in Patient Global Impression of change (PGIC).

Change from baseline in Schwab and England Activities of Daily Living (SE-ADL) 

Time to worsening of motor or non-motor symptoms as measured by MDS-UPDRS 

Time to start of dopaminergic PD treatment (levodopa or dopamine-agonists)
EXPLORATORY OUTCOME MEASURES
The exploratory outcome measures for this study are change from baseline to Week 52, to Week 
104 and to Part 3 Week 260 in:

MDS-UPDRS Part III total and Part III subscores central vs local ratings for consistency and 
accuracy

Time to worsening of motor or non-motor symptoms as measured by MDS-UPDRS or
starting dopaminergic treatment (levodopa or dopamine agonist)

Modified Hoehn & Yahr (mH&Y).

PDSS-2 total score and sub-scales.

SCOPA-AUT total score and subdomain scores. 

PDQ-39 total score and sub-scales

Digital Biomarkers and patient-reported outcomes (Smartphone and wrist-worn wearable 
assessments):

Diary questions (patient-reported outcome [PRO]) 

PAC-SYM questionnaire (PRO)

Hospital Anxiety and Depression Scale (HADS), anxiety (HADS-A), and depression (HADS-
D) sub-scales (PRO)

EQ-5D-5L questionnaire (PRO)

Sensor data collected during “Active Tests”, assessing motor symptoms (upper and lower 

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body movement, upper limb dexterity, voice/speech) and non-motor symptoms (including an 
electronic version of the Symbol Digital Modalities Test (eSDMT) to measure attention and 
executive function).

Sensor data collected during “Passive Monitoring” assessing activity, movement and motor 
symptoms associated with routine daily living.

Sensor data collected during “In-Clinic Assessments”, including the Timed Up and Go Test 
and selected items from the Berg Balance Scale.

Serum, plasma, and CSF biomarkers related to PD.

-synuclein pathology in peripheral nerves (skin biopsies in eligible participants).

DaT-SPECT binding ratio values for: striatum, caudate and putamen (average, ipsilateral 
and contralateral)

Diffusion tensor imaging (DTI) MRI for mean diffusivity and fractional anisotropy 

Resting state functional magnetic resonance imaging (rs-fMRI) for functional brain 
connectivity

Arterial spin labelling (ASL) MRI for cerebral blood flow.

NM-MRI for substantia nigra integrity.

Iron imaging for brain iron accumulation.

Time to start or change of co-medication for non-motor symptoms that may be related to PD 
(cognition, constipation, depression, anxiety, excessive daytime sleep, nocturnal sleep, 
urogenital symptoms/sexual dysfunction).

Start or change of co-medication for non-motor symptoms that may be related to imaging 
biomarkers (DAT Scan and ASL).

Parkinson-related effects on the loss of autonomic tone as measured by heart rate variability.

Composite score of MDS-UPDRS Part II (patient reported motor experiences of daily living) 
and MDS-UPDRS Part III (clinician rated motor signs of PD) sub-items 

MDS-UPDRS Part IV at Week 52, at Week 104 and Part 3 Week 260 in participants who 
started dopaminergic treatment (levodopa or dopamine agonist).
INVESTIGATIONAL MEDICINAL PRODUCT(S)
Test Product
The investigational medicinal product (IMP) in this study is RO7046015 for IV infusion, supplied 
as a concentrate for solution for infusion of 500 mg. Participants will receive IV infusions of 
RO7046015 high dose (4500 mg for BW 65 kg; 3500 mg for BW 65 kg), low dose (1500 mg; 
for all BW), or placebo, Q4W.  
Study drug should be given as IV infusion over 2 hours for the first three doses and if well
tolerated, the infusion time can be reduced to one hour in subsequent doses.
To enhance the tolerability of RO7046015 infusions, a dose titration regimen that may reduce the 
risk of IRRs will be implemented for the high dose, as follows: 2000 mg will be infused on Day 1 
followed by an up-titration to the full dose of 4500 mg (65 kg body weight) or 3500 mg (65 kg 
body weight) on the second infusion (Day 28) during Part 1. Participants receiving placebo 
during Part 1 and randomized to the high dose at the start of Part 2 (extension) will receive 2000 
mg IV on Week 56 followed by an up-titration to the full dose of 4500 mg (65 kg body weight) 
or 3500 mg (65 kg body weight) on the second infusion (Week 60).
Placebo 
Placebo formulation will not be provided. Participants randomized to placebo will receive an IV 
infusion of normal saline.

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Other
Symptomatic/dopaminergic PD medication and premedication before infusion are considered 
non-investigational medicinal products (NIMPs).
PROCEDURES
All assessments must be performed according to the Schedule of Assessments (SoA). 
The sequence of study assessments at each visit must be carried out according to the Sequence 
of Study Assessments.
STATISTICAL METHODS
PRIMARY EFFICACY ANALYSIS
The primary efficacy endpoint is the change in total MDS-UPDRS (sum of Parts I, II and III) from 
baseline to Week 52 (end of Part 1 of the study). It will be analyzed using a mixed-effect model 
for repeated measures (MMRM) with treatment (placebo and each active dose), background 
therapy (with or without MAO-B inhibitor treatment), age group (< 60 years vs 60 years), sex, 
DaT binding ratio at baseline and visit (seven levels) as fixed effects, treatment-by-visit 
interaction term, and the baseline value for total MDS-UPDRS (sum of Parts I, II and III) as a 
covariate; an interaction term between baseline MDS-UPDRS by visit will also be included. 
Within each participant, the model will incorporate an unstructured variance-covariance matrix 
for the random error terms. Observations from different participants are considered independent. 
For each active dose arm tested at the final analysis, this model will be used to test the null 
hypothesis of no treatment difference between the placebo arm and each active arm at a two-
sided -level of 20%, which corresponds to a one-sided -level of 10%.
Starting symptomatic PD treatment for the statistical analysis is defined as starting COMT 
inhibitors (entacapone, tolcapone), amantadine, anticholinergics, levodopa, dopamine agonists, 
or MAOB inhibitors and - for patients already on MAO-B inhibitors at baseline - also increases in 
dose or regimen of the MAOB inhibitor. Assessments performed after starting symptomatic PD 
treatment will not be included in the primary analysis. 
Missing values will be handled via the MMRM methodology.
The primary endpoint will also be summarized using descriptive statistics.
SECONDARY EFFICACY ANALYSES
For the endpoints of MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total, and Part 
III subscores, CGI-I, and PGI-C the information collected after symptomatic PD treatment or after 
an increase in MAO-B inhibitor therapy will be handled as in the primary analysis. The analysis 
of all other secondary endpoints will include all the information available regardless of start of 
symptomatic PD treatment.  
An important biomarker secondary endpoint is the change (between baseline and the Week 52 
visit) in DaT-SPECT uptake values in the ipsilateral putamen, which will be analyzed via an 
analysis of covariance (ANCOVA), regardless of intake of symptomatic PD therapy during the 
first 52 weeks. The model will include the baseline value of the respective DaT binding ratio as a 
covariate and age group, sex, treatment, background therapy as main effects. There will be no 
imputation for missing values.
Other secondary endpoints, which will also be analyzed at the end of Part 1 (after 52 weeks of 
treatment with either placebo or active treatment) include:

Change in MDS-UPDRS sub-scores from baseline to Week 52 for Part IA, Part IB, Part I 
total, Part II total, Part III total, and Part III subscores (bradykinesia, resting tremor and axial 
symptoms) analyzed with exactly the same MMRM approach as for the primary endpoint.

Change in MoCA total score from baseline to Week 52 analyzed with an analysis of 
covariance (ANCOVA). 

CGI-I will be analyzed using a logistic regression model, including the covariates described 
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
PGI-C will be analyzed using a logistic regression model, including the covariates described 
for the primary efficacy analysis.

Change in Schwab and England Activities of Daily Living (SE-ADL) from baseline to Week 
52 will be analyzed with ANCOVA.

Time to first occurrence of either of the following: 3 points change from baseline in MDS-
UPDRS Part I, or 3 points change from baseline in MDS-UPDRS Part II will be analyzed 
with a Cox proportional hazards model including the covariates described for the primary 
efficacy analysis along with a Kaplan-Meier Plot. 

Time to start dopaminergic treatment (levodopa or dopamine agonists) will be analyzed with 
a Cox proportional hazards model including the covariates described for the primary efficacy 
analysis, along with a Kaplan-Meier plot. Events in this analysis will only consider the start of 
levodopa or dopamine agonist. 
All secondary endpoints will be summarized using descriptive statistics. 
SAFETY ANALYSES
All randomized participants receiving at least one dose of study drug will be included in the 
safety analysis.
As appropriate, listings, summary tables and graphs will be provided for safety and tolerability 
assessments.
Safety data will be summarized using descriptive statistics. 
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES
Non-linear mixed effects modelling (with software NONMEM) will be used to analyze the sparse 
sampling dose-concentration-time data of RO7046015. Population and individual 
pharmacokinetic parameters (e.g., CL and central volume) will be estimated and the influence of 
various covariates (such as age, sex and body weight) on these parameters will be investigated. 
The data collected during the study will be pooled with data collected in the previous Phase I 
studies conducted in healthy volunteers and patients with PD. Secondary PK parameters such as 
AUC, Cmax and Ctrough at steady-state will be derived from the individual post-hoc predictions.
Interim Analyses
An interim analysis for efficacy may be conducted. If so, the efficacy interim analysis will be 
reviewed by the iDMC based on predefined criteria outlined in a statistical analysis plan. 
In addition to the primary analysis performed at Week 52, the Sponsor may choose to conduct
additional interim efficacy analyses during Part 2 and/or Part 3 of the trial. The decision to 
conduct an optional interim analysis and the timing of the analysis will be documented in the 
Sponsor’s trial master file prior to the conduct of the interim analysis. The interim analysis 
will be performed and interpreted by Sponsor study team personnel.

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SAMPLE SIZE JUSTIFICATION
A sample size of 100 randomized participants per group (300 participants for the three groups) 
has been chosen to obtain a power of approximately 80% at two-sided -level of 20%, which 
corresponds to a one-sided -level of 10%, for the pairwise comparison of each active dose arm 
to placebo. The power calculation was based on simulations of the mixed-effect model repeated 
measures (MMRM) analysis planned for the primary efficacy variable. Assessments performed 
while on any symptomatic treatment started after randomization will not be included in the 
analysis. The following assumptions were made for simulating the data:

Seven post-baseline assessment visits

An overall rate of missing values (due to participants starting symptomatic therapy or 
prematurely withdrawing from study medication during the 52-week placebo-controlled 
treatment period) of 25% in the placebo group and 20% in each dose group at Week 52, with 
incremental rates over the 52-week placebo-controlled period

A linear mean increase of the primary endpoint (natural progression) of eight points/year for 
the placebo arm, with a linearly increasing common standard deviation reaching nine points 
at Week 52.

An effect size of 0.33 (difference 3 points, relative reduction of progression 37.5%) for one 
dose group versus placebo at Week 52 with increasing magnitude of treatment difference 
over the placebo-controlled period.

A compound symmetry correlation structure assuming a correlation coefficient of 0.55 
between different visits.
These assumptions were derived from analyses based on the Parkinson’s Progression Markers 
Initiative (PPMI) database and various sources of information from the literature.
The sample size of 100 patients per arm provides also 76% power (20%, two-sided or 
10%, one-sided) to demonstrate a 37.5% reduction (effect size 0.318 based on assumption 
of decline over 52 weeks and standard deviation of 0.185 derived from the PPMI database) for 
the key secondary endpoint, the DaT-SPECT signal loss at Week 52, for the pairwise 
comparison of each active dose arm to placebo. 
No adjustments for multiple comparisons were incorporated into the analyses.
The sample size may be adjusted depending on the outcome of the iDMC safety review 
performed during the study or if assumptions (e.g., drop-out rate) used for sample size 
calculation need to be adapted. 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
AE
Adverse events
ADA
Anti-drug antibody
ALT
Alanine aminotransferase
ANS
Autonomic nervous system
aPTT
Activated partial thromboplastin time
ASA
Acetylsalicylic acid
ASL
Arterial spin labelling
AST
Aspartate aminotransferase
AUC
Area under the curve
BA
Bioavailability
BP
Blood pressure
CBF
Cerebral blood flow
CGI-I
Clinical Global Impression of Improvement 
CL
Systemic clearance
Cmax
Peak serum concentration
Ctrough
Trough serum concentration
CNS
Central nervous system
CRO
Contract research organization
CSF
Cerebrospinal fluid
CSR
Clinical study report
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTD
Common technical document
DaT-SPECT
Dopamine transporter imaging with single photon 
emission computed tomography
DNA
Deoxyribonucleic acid
DTI
Diffusion tensor imaging
DWI
Diffusion-weighted imaging
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic data capture
EEA
European Economic Area
ePRO
Electronic patient-reported outcome
EQ-5D-5L
European Quality of Life Questionnaire 5-level version
ESF
Eligibility Screening Form

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Abbreviation
Definition
eSDMT
Electronic Symbol Digit Modalities Test
EU
European Union
FDA
Food and Drug Administration
FDG-PET
2-deoxy-2-(18F) fluoro-D-glucose positron emission 
tomography
FLAIR
Fluid-attenuated inversion recovery
FSH
Follicle-stimulating hormone
GRE
Gradiant echo
HADS
Hospital Depression and Anxiety Scale
HBsAG
Hepatitis B surface antigen
HbcAb
Total hepatitis B core antibody
HCV
Hepatitis C
HDL
High density lipoproteins
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human immunodeficiency virus
H&Y
Hoehn and Yahr
ICH
International Conference on Harmonisation
iDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IMP
Investigational medicinal product
IND
Investigational New Drug 
INR
International normalized ratio
IP
Intraperitoneal
IRB
Institutional Review Board
IRC
Independent Review Committee
IRR
Infusion-related reaction
IRT
Item Response Theory
IUD
Intrauterine device
IV
Intravenous
IxRS
Interactive (voice/web) response system
LDH
Lactate dehydrogenase
LDL
Low density lipoproteins
LH
Luteinizing hormone
LPLV
Last patient, last visit
LPLO
Last participant, last observation
mAb
Monoclonal antibody
MAD
Multiple ascending doses

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Abbreviation
Definition
MAO-B
Monoamine oxidase B
MD
Multiple doses
MDS-UPDRS
Movement Disorder Society - Unified Parkinson's 
Disease Rating Scale
mITT
Modified intent-to-treat
MMRM
Mixed-effect model for repeated measures
MoCA
Montreal Cognitive Assessment
MRI
Magnetic resonance imaging
MTD
Maximal tolerated dose
NM
Neuromelanin
NOAEL
No-observed-adverse-effect level
OTC
Over-the-counter
PAC-SYM
Patient Assessment of Constipation Symptoms
PD
Parkinson’s disease
PDSS-2
Parkinson’s Disease Sleep Scale Revised Version 2
PK
Pharmacokinetic
PK/PD
Pharmacokinetic/pharmacodynamic
PPMI
Parkinson’s Progression Markers Initiative
PRO
Patient-reported outcome
PT
Prothrombin time
Q4W
Once every 4 weeks
QRS
QRS complex
QT
QT interval
QTc
QT corrected for heart rate
QTcF
QT corrected for heart rate using the Fridericia formula
RBC
Red blood cell
RBD
Rapid eye movement sleep behavior disorder
RBR
Research Biosample Repository
REM
Rapid eye movement
RNA
Ribonucleic acid
RR
RR interval
rs-fMRI
Resting state functional magnetic resonance imaging
SAD
Single ascending dose
SAE
Serious adverse event
SCOPA-AUT
Scales for outcomes in Parkinson’s disease autonomic 
dysfunction 
SD
Single dose

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Abbreviation
Definition
SE-ADL
Schwab and England Activities of Daily Living
SNc
Substantia nigra pars compacta
SoA
Schedule of assessments
SmPC
Summary of Product Characteristics
sMRI
Structural MRI
SNRI
Serotonin and norepinephrine reuptake inhibitors
SSRI
Selective serotonin reuptake inhibitors
SUSAR
Suspected unexpected serious adverse reaction
TEAE
Treatment-emergent adverse event
TSH
Thyroid-stimulating hormone
ULN
Upper limit of normal
US
United States
USPI
United States Prescribing Information
V
Volume of distribution
VAS
Visual analogue scale
WBC
White blood cell
WGS
Whole genome sequencing

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1.
BACKGROUND AND RATIONALE
1.1
BACKGROUND ON DISEASE
Parkinson’s disease (PD) is a progressive and chronic neurodegenerative disease 
estimated to affect between 7-10 million people worldwide (Parkinson’s Disease 
Foundation). In the United States (US), an estimated 725,000 people are affected 
(extrapolated from Kowal et al 2013) and over 50,000 new cases are reported every 
year (National Institute of Neurological Disorders and Stroke). Although 5 to 10 percent 
of patients are diagnosed before age 50, it is generally considered a disease that targets 
older adults, affecting one out of every 100 people over the age of 60 and it is more 
common in men than women (National Institute of Neurological Disorders and Stroke).
PD is pathologically characterized by the presence of Lewy bodies, composed of 
aggregated and phosphorylated -synuclein, in the subcortical regions of the brain 
(Spillantini et al 1997). While the presence of Lewy bodies in the substantia nigra pars 
compacta (SNc) is a pathologically-defining feature of PD, it is now well appreciated that 
-synuclein pathology can be present in other brain regions (e.g., olfactory bulb, medulla 
oblongata, midbrain, basal forebrain, neocortex, etc.) and is not restricted to the central
nervous system (CNS) as it is also abundantly present in the peripheral nervous system. 
Extra-nigral -synuclein pathology appears to precede the pathology in the SNc (Braak 
et al 2003) and presence of -synuclein pathology has been visualized in the peripheral 
nervous system using ante-mortem biopsy and post-mortem autopsy specimens from 
various regions of the body, such as colon, salivary glands and skin (for review see 
Malek et al 2014).
While the exact cause of the disease is unknown, there is a strong correlation between 
motor symptoms and the loss of the dopaminergic neurons in the substantia nigra and 
the presence of -synuclein containing Lewy bodies and Lewy neurites in both central 
and peripheral nervous systems (Beach et al 2009). Moreover, genetic evidence 
indicates that both missense mutations (Kay et al 2008) and increased production of 
-synuclein due to genomic duplication or triplication of the -synuclein gene (SNCA) 
(Singleton et al 2003, Ibanez et al 2004) can cause early onset autosomal dominant 
Parkinson’s disease.
At the time of diagnosis, patients may present with prominent motor and non-motor 
symptoms. Motor symptoms often include resting tremor, limb stiffness or rigidity, 
slowness of movement (i.e., bradykinesia), and gait or balance problems (i.e., postural 
instability). Non-motor symptoms, present in most patients, can often dominate the 
clinical presentation and may include cognitive decline, depression, constipation, 
anosmia, pain, and sleep disorders. A diagnosis of PD is typically supported by 
asymmetric onset of motor symptoms and by a substantial and sustained response to 
levodopa or dopaminergic agents (Gibb and Lees 1988; Gelb et al 1999; Bhidayasiri and 
Reichmann 2013). As the disease slowly progresses, there is ongoing decline and 
debilitation. Patients are at high risk for the development of psychiatric illness and 

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dementia with disease-related complications that can reduce life-expectancy (de Lau et 
al 2005; Weintraub and Burn 2011).
Current treatments for PD manage the early motor symptoms of the disease, mainly 
through the use of dopamine replacement therapy and dopamine receptor agonists. 
Treatment with levodopa and other dopaminergic agents temporarily addresses the 
motor symptoms and is used extensively. However, this does not reverse, slow or halt 
pathological processes related to the disease. As the disease progresses and dopamine 
neurons continue to be lost, these drugs become less effective at controlling the 
symptoms. 
Patients who take these medications often develop side-effects such as motor 
complications (e.g., response oscillations, wearing off phenomena and drug-induced 
dyskinesias), as well as nausea, daytime somnolence, sleep attacks, orthostatic 
hypotension or impulse control disorders (Sprenger and Poewe 2013). Symptomatic 
treatment of non-motor symptoms of PD, e.g., sleep disturbances, anxiety and 
depression, are also available. To date, there are no approved treatments that have 
demonstrated protection of neurons or modification of the disease course.
1.2
BACKGROUND ON RO7046015
RO7046015 (PRX002) is an immunoglobulin class G1 (IgG1) humanized monoclonal 
antibody (mAb) directed against an epitope in the C-terminus of human -synuclein. The 
molecule is composed of two heterodimers. Each of the heterodimers is composed of a 
heavy polypeptide chain of ~48 kDa (446 amino acids) and a kappa light polypeptide 
chain of ~24 kDa (220 amino acids). The antibody protein has a humanized amino acid 
sequence with a total molecular mass of approximately 147 kDa. There are two binding 
sites for the -synuclein epitope per antibody molecule.
Note: RO7046015 is also known as prasinezumab but in this document, RO7046015 
will be used.
For details on non-clinical and clinical studies, see the RO7046015 Investigator’s 
Brochure.
1.2.1
Previous Non-Clinical Studies
Non-clinical studies showed that RO7046015 and/or its murine form, 9E4, bind to 
monomeric human -synuclein with nanomolar affinity (KD approximately 20-35 nM) and 
high specificity for -synuclein over other members of the synuclein family (- and 
-synuclein). RO7046015 binding affinity was comparable between human and 
cynomolgus monkey -synuclein but was not measurable against murine -synuclein, 
nor was binding to rat or rabbit -synuclein detected. The epitope for RO7046015/9E4 
binding is included in amino acids 118-126 of human -synuclein. RO7046015 and 9E4 
bind to fibrillar -synuclein, which is evident by their capacity to immunostain thioflavin-
positive Lewy bodies and Lewy neurites in PD brain samples. Furthermore, the apparent 

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affinity/avidity of those antibodies to the pathological aggregated forms of -synuclein 
was demonstrated to be substantially higher compared to affinity/avidity to monomers. 
An in vitro model of cell-to-cell transmission of -synuclein was established and used to 
demonstrate that 9E4 blocks the intercellular transmission of -synuclein. In vivo efficacy 
was evaluated in two transgenic mouse models of -synucleinopathy, the Line D and 
Line 61 models, using 9E4 to ensure efficient engagement of Ig receptor function by 
utilizing a mouse-in-mouse system. In both transgenic models, weekly intraperitoneal (IP) 
administration of 9E4 over 5-6 months reduced brain pathology manifested as -
synuclein deposits in cortical and subcortical regions, protected against synaptic loss, 
and prevented the decline in cognitive and motor behavior. 
In a 26-week cynomolgus monkey study, there were no specific effects of intravenous 
(IV) infusion of RO7046015 on any safety pharmacology endpoints, including the 
cardiovascular system, at dose levels up to 300 mg/kg/week (the maximum dose 
studied). There were also no effects on the respiratory system up to 100 mg/kg/week 
(maximum dose studied) for 13 weeks. In GLP toxicology studies, RO7046015 was well 
tolerated and no target organ toxicity has been described in the monkey up to 
300 mg/kg/week for 26 weeks. At the end of the 26-week GLP toxicology study, the 
average serum AUC0-28d and Cmax 300 mg/kg/week IV were 894,000 g h/mL (average 
AUC0-7d of 223,500 g h/mL4 weeks) and 7030 g/mL, respectively. Toxicokinetic 
parameters were generally similar after first and last administrations and there was a 
tendency for higher systemic exposure in males compared to females. Following 
repeated IV administration (100 mg/kg IV infusion once weekly for 13 weeks) in 
cynomolgus monkey, RO7046015 was demonstrated to reach the cerebrospinal fluid 
(CSF) (0.1-0.4% CSF/serum AUC ratio).
1.2.2
Previous Clinical Studies
RO7046015 or placebo has been administered as an IV infusion in three Phase I clinical 
studies. A total of 64 healthy subjects and 80 participants with PD have taken part in 
these studies, of whom 48 healthy subjects and 55 participants with PD have received 
prasinezumab as an IV infusion.
Study PRX002-CL001 (BP29477; single-ascending dose [SAD] in healthy subjects in 
the United States [US]) was a randomized, double-blind, placebo-controlled study 
which assessed the safety and PK of RO7046015 administered to 40 healthy 
participants in 5 ascending-dose cohorts in which participants were randomly assigned 
to receive a single IV infusion of study drug (0.3, 1, 3, 10 or 30 mg/kg; n6/cohort) or 
placebo (n2/cohort). Serum RO7046015 exposure parameters increased proportionally 
with the dose of RO7046015 over the dose range of 0.3 mg/kg to 30 mg/kg and resulted 
in dose- and time-dependent reductions in mean serum free -synuclein levels (unbound) 
and increases in mean serum total -synuclein levels (bound plus free). RO7046015 
demonstrated favorable safety, tolerability, and pharmacokinetic profiles at all doses 

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tested, with no immunogenicity. No serious adverse events, discontinuations as a result 
of adverse events, or dose-limiting toxicities were reported (Schenk et al 2016).
Study JP40211 (SAD study in healthy male Japanese subjects) was a randomized, 
double-blind, placebo-controlled study SAD study which assessed the safety and 
tolerability of RO7046015 and evaluated PK of RO7046015 in 24 healthy Japanese male 
participants in three ascending-dose cohorts in which participants were randomly 
assigned to receive a single IV infusion of study drug (10, 30 or 60mg/kg; n 6/cohort) 
or placebo (n 2/cohort). Across the dose range of 10 mg/kg to 60 mg/kg, the PK of 
RO7046015 in healthy Japanese subjects were similar to that of healthy subjects in the 
US in the PRX002-CL001 SAD study. In addition, RO7046015 demonstrated favorable 
safety, tolerability, and pharmacokinetic profiles comparable to the healthy subjects in 
the US, with no immunogenicity. No serious adverse events, discontinuations because 
of adverse events, or dose-limiting toxicities were reported.
Study PRX002-CL002 (multiple-ascending dose (MAD) study in participants with mild-
to-moderate PD) (Jankovic et al 2018) was a randomized, double-blind, placebo-
controlled study which assessed the safety, PK and pharmacodynamics of RO7046015 
administered to 80 participants with mild to moderate PD (Hoehn and Yahr [H&Y] Stages 
I-III), in six ascending-dose cohorts in which patients were randomly assigned to receive 
study drug (0.3, 1, 3, 10 mg/kg, n8/cohort or 30, 60 mg/kg, n12/cohort) or placebo 
(n4/cohort) for three IV infusions administered every 28 days. The PK in patients was 
similar to that in healthy volunteers. Exposure increased approximately proportionally
with increasing dose. The highest mean exposure (at 60 mg/kg dose) in terms of Cmax
and AUCtau after the third dose was 1160 g/mL and 168000 g h/mL, respectively, and 
well below the no-observed-adverse-effect level (NOAEL) exposure in cynomolgus
monkey. A population PK model described the pharmacokinetics very well, estimating 
clearance as 2.5-3-fold higher than for a typical IgG1 and the effective half-life as 13-15 
days (see RO7046015 Investigator’s Brochure). The reduction in free serum -synuclein 
levels were comparable to those seen in healthy subjects after the first dose, and more 
pronounced after the third dose.
RO7046015 was well tolerated without any reports of treatment-emergent serious 
adverse events (SAEs). The most frequently reported mild to moderate treatment-
emergent adverse events (TEAEs) in the MAD study in PD patients (PRX002-CL002, 
see RO7046015 Investigator’s Brochure) included constipation (9.1%), infusion-related 
reactions (IRRs) (7.3%), diarrhea (5.5%), peripheral edema (5.5%) and post-lumbar 
puncture syndrome (5.5%). Mild to moderate IRRs, that all resolved were limited to the 
60 mg/kg dose cohort and were observed in 4 of the 12 treated patients. One patient 
had a confirmed anti-drug antibody (ADA) titer to RO7046015; however, this patient 
received placebo indicating that the finding was a false positive. No clinically relevant 
trends in clinical laboratory data, physical examination, vital sign, or electrocardiogram 
(ECG) parameters were observed after dosing, and no TEAE trends related to these 
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1.3
STUDY RATIONALE AND BENEFIT–RISK ASSESSMENT
1.3.1
Study Rationale
Current treatments for PD manage the early motor symptoms of the disease, mainly 
through the use of dopamine replacement therapy and dopamine receptor agonists. 
However, these treatments do not reverse, slow or halt the pathological processes 
related to the disease. As the disease progresses and dopamine neurons continue to be 
lost, symptomatic treatments become less effective and patients develop side-effects 
such as motor complications including response oscillations, wearing-off phenomena 
and drug-induced dyskinesias (Sprenger and Poewe 2013). To date, there are no 
approved treatments which have demonstrated protection of neurons or modification of 
the disease course.
Clinical and non-clinical evidence suggest that aggregated forms of -synuclein 
self-propagate and spread between interconnected nervous system regions, contributing 
to the progression of PD. Strong non-clinical evidence suggests that RO7046015, a 
monoclonal antibody designed to preferentially target aggregated forms of -synuclein, 
has the potential to slow or halt the progression of PD by preventing cell-to-cell 
spreading of -synuclein pathology (Section 1.2.1 and RO7046015 Investigator’s 
Brochure).
Disease-modifying (neuroprotective) treatment is expected to be most effective in early 
PD patients who still have a substantial number of vulnerable neurons which could be 
protected. The most suitable population in which to test the hypothesis that treatment 
with RO7046015 will slow or halt the progression of PD is in patients with early-stage 
clinical PD, DaT-SPECT-confirmed dopaminergic deficit and rapid disease progression 
that is not yet modified by symptomatic treatment with levodopa or dopaminergic 
agonists. 
Proof-of-concept (POC) will be demonstrated by a reduction in clinical progression of PD 
symptoms measured using a well-characterized scale, the Movement Disorder Society 
(MDS)-sponsored revision of the Unified Parkinson’s Disease Rating Scale (UPDRS). 
The UPDRS is a well-validated scale that has been used for many pivotal studies for the 
symptomatic treatment of PD. In order for a Phase II POC study to assess the disease-
modifying potential of study treatment, it is essential to define a population that optimizes 
the rate of progression of the placebo population when using the Movement Disorder 
Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Based on analysis of 
data from the Parkinson’s Progression Markers Initiative (PPMI) study (Marek et al 2011, 
Simuni et al 2015), a 52-week treatment duration is expected to be sufficient to 
demonstrate relevant between-group differences due to the effects of a 
disease-modifying treatment that changes the rate of progression in early stage PD 
patients without dopaminergic treatment.

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Participants completing Part 1 of the study (52-week placebo-controlled period) with a 
pre-defined minimum of infusions and assessments will be offered the option to continue 
with Part 2 (52-week all-on-active-treatment extension) and receive RO7046015 
infusions Q4W (blinded to dose) until Week 104 to further study the long-term safety and 
clinical effects of RO7046015 and to offer potential benefits of treatment with 
RO7046015 to all participants (see Section 3.1.1 for further details).
Participants completing Part 2 of the study (52-week all-active-treatment extension) 
and completing the 12 weeks treatment free follow-up will be offered the option to 
participate in Part 3 (260 weeks all-on-active-treatment extension followed by 12 weeks 
treatment free follow-up). In Part 3 participants will be administered RO7046015 
infusions Q4W (blinded to dose until Phase III study dose has been identified) until 
Part 3 Week 260 to further study the long-term safety and clinical effects of 
RO7046015 and to continue to offer potential benefits of treatment with RO7046015 to 
all participants. When the Phase III study dose is identified, based on Part 1 data 
analysis, all participants will receive the Phase III dose for the remaining duration of 
this study.
1.3.2
Benefit-Risk Assessment
RO7046015 and its murine form, 9E4, bind to monomeric human (and cynomolgus 
monkey) -synuclein with nanomolar affinity and with substantially higher apparent 
affinity/avidity to the pathological aggregated forms of -synuclein. In vitro data show 
that 9E4 can block cell-to-cell transmission of -synuclein. In two transgenic mouse 
models of -synucleinopathy, weekly intraperitoneal (IP) administration of 9E4 over 
5-6 months reduced brain pathology (-synuclein deposits) in cortical and subcortical 
regions, protected against synaptic loss, and prevented the decline in cognitive and 
motor behavior. Reduction of brain pathology and improvement of cognition was 
observed after 1 mg/kg weekly IP, and additional beneficial effects on other behavioral 
endpoints were observed after 10 mg/kg weekly IP. For further details, see the 
RO7046015 Investigator’s Brochure.
To date, no treatments have been identified that change the neuropathological 
progression of PD. Consequently, there are no predictive biomarkers and the 
translatability of available PD animal models to man is not known. Furthermore, 
there are no biomarkers to measure target engagement (aggregated -synuclein) in the 
CNS in humans. Therefore, a fixed (flat) high dose IV (4500 mg for BW 65 kg; 3500 mg 
for BW 65 kg), corresponding to the maximum dose tested in Phase I clinical studies 
(60 mg/kg IV) will be tested in the Phase II study. This dose achieves average trough 
serum concentrations in the range of those observed after 10 mg/kg weekly IP dose in
the transgenic mouse model (approximately 70 g/mL). In addition, a second fixed (flat) 
dose of 1500 mg IV (for all BW), that achieves serum trough concentration levels above 
those noted with 1 mg/kg in the mouse efficacy model (approximately 17 g/mL, which is 
achieved with a human Q4W dose of 800 mg) will be tested as a potential low 

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efficacious dose with sufficient separation from the maximum dose to allow exposure-
response analyses (see Section 3.2.3).
In a 26-week cynomolgus monkey study, there were no specific effects of IV infusion of 
RO7046015 on any safety pharmacology endpoints, including the cardiovascular system, 
at dose levels up to 300 mg/kg/week (the maximum dose studied). RO7046015 was well 
tolerated and no target organ toxicity has been described up to 300 mg/kg/week for 
26 weeks. The average AUC0-28d and Cmax values at 300 mg/kg/week were 
894,000 g h/mL and 7030 g/mL, respectively.
In clinical studies conducted with RO7046015, the highest mean exposure (after three 
infusions with a 60 mg/kg dose) in terms of Cmax and AUCtau after the third dose was 
1160 g/mL and 168000 g h/mL, respectively, and well below the no-observed-
adverse-effect level (NOAEL) exposure in cynomolgus monkey (Cmax six times and AUC 
five times).
In the clinical studies with healthy volunteers or PD patients, no treatment-emergent 
SAEs were reported (Section 1.2.2). No studies were terminated prematurely. Mild to 
moderate IRRs were observed in 4 of 12 treated patients in the 60 mg/kg dose cohort in 
the MAD study (PRX002-CL002, see RO7046015 Investigator’s Brochure). IRRs have 
been reported with the use of many antibodies and other biologic therapies, usually with 
the first or second infusion of a therapeutic monoclonal antibody and they tend to be 
dose-related. In order to reduce the occurrence and potential impact of IRRs, several 
measures have been included in the current protocol, such as dose titration, two 
different flat doses (based on body weight) for the high dose group, slower infusion time 
and premedication for the first three infusions, as well as implementation of an 
independent data monitoring committee that will monitor IRRs and other adverse event 
(AE) reports and may reduce the highest dose level if necessary (see Section 4.4.2 and 
Section 5.2.1). As of 29 November 2019, 84 participants out of 316 participating in the 
currently ongoing BP39529 Phase II study and receiving either prasinezumab or 
placebo had at least one IRR: 50 participants experienced IRR at the highest grade 1; 32 
experienced IRR at the highest Grade 2 and 2 pts experienced IRR at the highest of 
Grade 3 (see RO7046015 Investigator’s Brochure). Review of blinded data from the 316 
safety evaluable participants in the ongoing study (BP39529) shows a safety profile 
that is consistent with that observed in the Phase I study (PRX002-CL002).
A benefit of RO7046015 in patients has not yet been demonstrated and the study 
described in this protocol is designed to assess this. Based on the evidence collected to 
date supporting a potential beneficial effect, the high unmet medical need for therapies 
which may modify the course of disease progression in PD, and the observed safety 
profile to date, further clinical development of RO7046015 is supported.

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2.
OBJECTIVES
2.1
PRIMARY OBJECTIVE 
The primary objective of this study is:

To evaluate the efficacy of RO7046015 versus placebo at Week 52 in participants 
with early PD (H&Y Stages I-II) who are untreated or treated with monoamine 
oxidase B (MAO-B) inhibitors since baseline, as measured by change from baseline
on the MDS-UPDRS Total Score (sum of Parts I, II and III).
2.2
SECONDARY OBJECTIVES
The secondary objectives of this study are:

To evaluate the effects of RO7046015 versus placebo at Week 52, in participants 
with early PD (H&Y Stages I-II) who are untreated or treated with MAO-B inhibitors 
since baseline, on the following:
–
MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total and Part III 
subscores 
–
Dopamine transporter imaging with single photon emission computed 
tomography (DaT-SPECT) in the ipsilateral (to the clinically dominant side) 
putamen
–
Montreal Cognition Assessment (MoCA) total score 
–
Clinical Global Impression of Improvement (CGI-I) 
–
Patient Global Impression of Change (PGIC)
–
Schwab and England Activity of Daily Living (SE-ADL) score
–
Time to worsening in motor or non-motor symptoms 
–
Time to start of dopaminergic PD treatment (levodopa or dopamine agonists) 
–
Safety and tolerability of RO7046015.

To evaluate the safety and tolerability of treatment with RO7046015 for up to 
104 weeks (Part 2) and up to Part 3 Week 260, with or without concomitant 
dopaminergic treatment.

To evaluate the immunogenicity of RO7046015.

To describe the PK of RO7046015 using population PK modelling.
2.3
EXPLORATORY OBJECTIVES
The exploratory objectives of this study are:

To compare consistency and accuracy in MDS-UPDRS Part III total, Part III 
subscores centrally rated by video-tapes vs locally rated by the site (in Part 1 and 
Part 2 only)

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
Time to worsening in motor or non-motor symptoms or starting dopaminergic PD 
treatment (levodopa or dopamine agonist) 

To evaluate the effect of RO7046015 versus placebo over 52 weeks, on change 
from baseline in:
–
Modified Hoehn and Yahr, Hospital Anxiety and Depression Scale (HADS), 
Patient Assessment of Constipation Symptoms (PAC-SYM), scales for 
outcomes in Parkinson’s disease autonomic dysfunction (SCOPA-AUT), 
Parkinson’s Disease Sleep Scale Revised Version 2 (PDSS-2), 39-item 
Parkinson’s Disease Questionnaire (PDQ-39), European Quality of Life 
Questionnaire 5-level version [EQ-5D-5L] and Smartphone and wrist-worn 
wearable assessments.
–
Serum, plasma, CSF, skin and imaging biomarkers related to PD.

To evaluate clinical and biomarker outcomes (as outlined above) over a period of up 
to 104 weeks including data from the one-year extension (Part 2) (all-participants-
on-treatment, blinded to dose) with or without concomitant dopaminergic treatment. 

To evaluate clinical and biomarker outcomes (as outlined above) in the five-year 
extension (Part 3) (all-participants-on-treatment, blinded to dose until Phase III 
study dose has been identified) with or without concomitant dopaminergic 
treatment. 

To evaluate the dose-exposure-response (pharmacokinetic/pharmacodynamic 
[PK/PD]) relationship for MDS-UPDRS, DaT-SPECT and other functional, biomarker 
and safety parameters.

To evaluate an immunohistochemical assay for -synuclein pathology in peripheral 
nerves (skin biopsy samples from randomized participants and DaT-SPECT screen 
failures).

To assess time to start or change of co-medication for non-motor symptoms that 
may be related to PD (cognition, constipation, depression, anxiety, excessive 
daytime sleep, nocturnal sleep, urogenital symptoms/sexual dysfunction).

To assess start or change of co-medication for non-motor symptoms that may be 
related to imaging biomarkers (DAT Scan and ASL).

To assess Parkinson-related effects on the loss of autonomic tone as measured by 
heart rate variability. 

To evaluate motor progression as assessed by a composite score of MDS-UPDRS 
Part II (patient reported motor experiences of daily living) and MDS-UPDRS Part 
III (clinician rated motor signs of PD) sub-items 

To assess motor complications as assessed by MDS-UPDRS Part IV at Week 52, at 
Week 104 and Part 3 Week 260 in participants who started dopaminergic treatment 
(levodopa or dopamine agonist).

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3.
STUDY DESIGN
3.1
DESCRIPTION OF STUDY
3.1.1
Overview of Study Design
This is a multicenter, Phase II study to evaluate the effect of IV administration of 
RO7046015 in participants with early stage (H&Y Stages I-II) PD. Participants will be 
eligible if they have idiopathic PD with bradykinesia plus one of the other cardinal signs 
of PD (resting tremor, rigidity) being present, without any other known or suspected 
cause of PD (adapted from the MDS Clinical Diagnostic Criteria for Parkinson’s Disease, 
see Postuma et al 2015) and are either untreated or treated only with MAO-B inhibitor. 
The study will consist of three parts: a 52-week, double-blind, placebo-controlled 
treatment period (Part 1) after which eligible participants will continue into an all-
participants-on-treatment (RO7046015) blinded to dose extension for an additional 
52 weeks (Part 2). Participants who complete Part 2 (including the 12-week treatment 
free follow up visit assessing long term safety and efficacy of RO7046015) will be 
offered participation in Part 3 (all-participants-on-treatment (RO7046015) blinded to 
dose until Phase III study dose has been identified) for an additional 260 weeks (see
Section 3.1.1.3 for further details on Part 3).
An overview of the study design is provided in Figure 1.
3.1.1.1
Part 1
During Part 1 of the study, participants will receive IV infusions of RO7046015 or 
placebo Q4W over a period of 52 weeks.
Approximately 300 participants will be randomized with a 1:1:1 allocation ratio to placebo, 
or one of the two active treatment doses: high dose (4500 mg for body weight65 kg; 
3500 mg for body weight65 kg), low dose (1500 mg; for all body weights). The number 
of randomized participants could be increased to a maximum of 360 depending on the 
outcome of the safety review by the independent Data Monitoring Committee (iDMC;
Section 3.1.2.1). The sample size may also be adjusted if the initial assumptions on 
dropout rate and likelihood to start dopaminergic therapy as described in Table 4 are 
different from the actual values observed. If that is the case, the Sponsor may increase 
enrolment up to 20% of the total sample size. The aim of this increase in sample size is 
to ensure that the pairwise comparison of each active dose arm to placebo remains 
adequately powered (see Section 6.1).
Randomization will be stratified by sex, age group (60 years vs 60 years), and prior 
background therapy with MAO-B inhibitor at randomization (Yes vs No).
To enhance the tolerability of RO7046015 infusions, a dose titration regimen that may 
reduce the risk of IRRs (Gazyvaro SmPC) will be implemented for the high dose, as 
follows: 2000 mg will be infused on Day 1 followed by an up-titration to the full dose of 

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4500 mg (65 kg body weight) or 3500 mg (65 kg body weight) on the second infusion 
(Day 28) during Part 1.
Only early stage PD patients with a clinical condition not requiring dopaminergic PD 
medication at baseline and not expected to require dopaminergic treatment within 
12 months from baseline will be eligible to participate in the study. Patients with a history 
of stable parkinsonian symptoms who are on a stable dose of MAO-B inhibitor 
(rasagiline or selegiline) for at least 90 days prior to baseline may also be included (see 
Section 4.5.1). 
Participants are expected to not start dopaminergic (levodopa or dopamine agonist) or 
other symptomatic PD therapy (as defined in Section 4.5.3) during Part 1. Some 
participants may experience worsening of their symptoms to an extent that they are 
unable to tolerate it in their personal or professional life. These participants may start 
dopaminergic or symptomatic PD treatment according to local guidelines after 
completing the assessments at the “prior to start of dopaminergic treatment” visit 
according to the schedule of assessments (SoA; Appendix 1) and the Investigator must 
record the reasons and the type and dose of dopaminergic or symptomatic PD treatment 
started. Participants who have started dopaminergic or symptomatic PD treatment will 
then continue in the study, as per their regular scheduled study visits. 
For the main analysis of the primary endpoint and other efficacy endpoints that are 
sensitive to symptomatic PD treatment (such as MDS-UPDRS part III, PGIC, CGI-I), only 
data up to the last measurement before start of dopaminergic treatment will be used. 
Data after start of symptomatic PD treatment will be included in safety, sensitivity, 
exploratory and biomarker evaluations as appropriate.
All participants, including those that have started symptomatic PD treatment, will be 
eligible to participate in Part 2 if they have completed Part 1 with the predefined 
minimum of infusions and assessments as defined in Section 3.1.1.2.
3.1.1.2
Part 2
Part 2 is a one-year all-participants-on-treatment, blinded to dose extension.
Participants must meet the following criteria to enter Part 2: DaT-SPECT and magnetic 
resonance imaging (MRI) scans completed at Screening and Week 52 and have 
received at least 10 doses of study treatment (RO7046015 or Placebo) during the first 
52 weeks of the study (Part 1). Participants may initiate or change symptomatic PD 
treatment (including dopaminergic treatment) as per standard of care during Part 2 (see 
Section 4.5.3).

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For Part 2, participants who complete the initial placebo-controlled part and fulfil the 
criteria mentioned above will switch into the extension as follows:

Participants initially randomized to placebo will be re-randomized to one of the two 
active doses using a 1:1 allocation ratio. 
Randomization will be stratified by: dopaminergic therapy since start of the study 
(Yes versus No), age group (60 versus60) and prior background therapy with 
MAO-B inhibitor (Yes versus No). For age group and prior background therapy with 
MAO-B inhibitor, the values collected for Part 1 will be used. 
Participants receiving placebo during Part 1 and randomized to the high dose at the 
start of Part 2 (extension) will receive 2000 mg IV on Week 56 followed by an 
up-titration to the full dose of 4500 mg (65 kg body weight) or 3500 mg (65 kg 
body weight) on the second infusion (Week 60).

Participants initially randomized to the active dose will remain on their dose.
3.1.1.3
Part 3
Part 3 is a 5-year extension in which all participants will be on treatment. Participants
will be blinded to dose until the Phase III study dose is identified (Note: this dose will 
not exceed the high dose tested in the present BP39529 study). Once the Phase III study 
dose is identified, participants will be switched to that dose (if applicable). 
Participants must meet the following criteria to enter Part 3: 

Having completed Part 2 (i.e., completed Week 104 visit) as well as the 12-week
treatment free follow up visit. Participants may initiate or change symptomatic PD 
treatment (including dopaminergic treatment) as per standard of care during Part 
3 (see Section 4.5.3).

Not having received another investigational medication during the treatment free 
period (i.e., between Week 104 visit and Part 3 Week 1 visit).

Participation in Part 3 not deemed inappropriate by the investigator (e.g., patient 
with serious medical condition or other concerns that preclude their safe 
participation in Part 3 or their ability to comply with the required procedures 
should not be enrolled)
Note: At the time Part 3 will be initiated and locally approved, the participants can be 
in one of the 3 following situations:

Situation #1: Participants have completed Part 2 and the 12-week free of treatment 
follow up (including the follow up visit)

Situation #2: Participants have completed Part 2 but are still in the 12-week free of 
treatment follow up (follow up visit not done yet)

Situation #3: Participants have not yet completed Part 2

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In any case, the time window between the date the protocol has been initiated and 
approved as per local regulation and the date of Part 3 Week 1 visit should not exceed 2 
months.   
If eligible, all these patients will be offered the possibility to participate in Part 3. The 
section below details how eligible participants will enter Part 3 according to their 
status in the study at the time Part 3 is initiated and approved as per local regulation.

Situation #1: Participants having already completed Part 2 and are free of 
treatment for more than 12-weeks at the time Part 3 is initiated and locally 
approved: 
As long as the Phase III study dose is not identified, patients will take the 
same dose they received in Part 2. Dosing will be restarted as an IV infusion at 
the same infusion rate used in Part 2. In case of occurrence of IRR, 
instructions provided in Section 5.2.1 will be followed.  Once the Phase III
study dose is identified, and if applicable, participants will be switched to this 
dose as soon as possible. 

Situation #2: Participants having completed Part 2 (i.e., Week 104 visit completed)
and being in the 12-week treatment free follow up period at the time Part 3 is 
initiated and locally approved: 
Patients will be asked to complete the 12-week treatment free period as well as
the 12-week treatment free follow-up visit as per protocol. Within four weeks 
after the follow-up visit, they will be asked to start Part 3 (Note: Part 3 Week 
1 visit cannot take place the same day as the 12-week treatment free follow-up 
visit). 
- If the Phase III study dose is not identified at that time, patients will take the 
same dose they received in Part 2. Dosing will be restarted as an IV infusion at 
the same infusion rate used in Part 2. In case of occurrence of IRR, 
instructions provided in Section 5.2.1 will be followed.  Once the Phase III 
study dose is identified, and if applicable, participants will be switched to this 
dose as soon as possible. 
- If the Phase III study dose is already identified at that time, dosing will be 
restarted with Phase III study dose as an IV infusion at the same infusion rate 
used in Part 2. In case of occurrence of IRR, instructions provided in Section 
5.2.1 will be followed.  

Situation #3: Participants not having completed Part 2 at the time Part 3 is 
launched and locally approved:
As per inclusion criteria, all participants have to have completed Part 2 to be 
eligible to Part 3, thus these participants will be asked to complete Part 2 (i.e.,
completed Week 104 visit and the 12-week treatment free follow-up visit). 
Within four weeks after 12-week treatment free follow up visit has been 
completed (but not on the same day this visit has been completed), dosing will 
be restarted with Phase III study dose as IV infusion at the same infusion rate 

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used in Part 2. In case of occurrence of IRR, instructions provided in Section 
5.2.1 will be followed.  
Figure 1
Study Design
3.1.1.4
Duration of Study
The study for each patient will be divided as follows:

Screening: Up to 8 weeks

Treatment period: 364 weeks (52 weeks in Part 1, 52 weeks in Part 2 and 260 weeks 
in Part 3)

Safety Follow-up: up to 12 weeks after cessation of double-blind treatment 
(regardless of whether cessation of treatment occurs at the end of or during Part 1 
or Part 2).     

Part 3 Safety Follow-up: 12 weeks after cessation of treatment (regardless of 
whether cessation of treatment occurs at the end of or during Part 3).
Day 1 will be designated as the first day the study drug (RO7046015 or placebo) is 
administered.

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3.1.2
Independent Data Monitoring Committee
This study will utilize an independent Data Monitoring Committee (iDMC), which will 
monitor safety and may also conduct an efficacy interim analysis review, if deemed 
necessary by the Sponsor. The interim analyses will be conducted by an external 
statistical group and other external specialists, as appropriate, and reviewed by the 
iDMC. Interactions between the iDMC and the Sponsor will be carried out as specified in 
the iDMC Charter. Sponsor personnel will not have access to the results of these data 
analyses.
The iDMC will be composed of:  

Three to four independent clinical experts in the field of Parkinson’s disease 
(external to Roche)

An independent statistician (external to Roche)
3.1.2.1
Review of Safety Data by the Independent Data Monitoring 
Committee
An iDMC will be used during the study to monitor and ensure the participants’ safety. 
The iDMC will be unblinded at the aggregate and individual level to review and evaluate 
safety data including AEs/SAEs, ECGs, and vital signs. No sponsor personnel will have 
access to the data displays reviewed by the iDMC. The iDMC will make 
recommendations to the Sponsor on the conduct of the clinical trial in accordance with 
the remit of the iDMC documented in the iDMC charter. In particular, the iDMC may 
recommend stopping enrollment in the highest dose cohort and introducing a new mid-
dose cohort (3000 mg). In this case, participants already enrolled at a higher dose will 
continue in the study with the new mid-dose of 3000 mg (see Section 3.2.3). 
The first and second iDMC meetings for review of safety data will take place after 
approximately 30 participants (approximately 10 participants per arm) and 
60 participants (approximately 20 participants per arm), respectively, have received their 
first three infusions. The iDMC may be convened at an earlier or at additional time-points 
if warranted by safety considerations or for other reasons (for further details see the 
separate iDMC Charter). 
Note that if the high-dose is discontinued, the sponsor may increase the sample size (by 
a maximum of 20%) and/or change the allocation ratio to ensure that the number of 
participants required to have approximately 80% power for the comparison between the 
new mid-dose and placebo is maintained (see Section 6.1).
3.1.2.2
Review of Efficacy Data by the Independent Data Monitoring 
Committee
The decision to conduct an optional interim analysis for efficacy, along with the rationale, 
timing, and statistical details for the analysis, will be documented in a Statistical Analysis 
Plan (SAP). 

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3.1.3
End of Study
The end of the study is defined as the date when the last participant last observation 
(LPLO) occurs at the follow-up visit. LPLO is expected to occur approximately 388
weeks after the last participant is enrolled, or earlier in the case that the study is 
discontinued following any of the planned interim analyses.
The primary analysis will be performed after all active participants have completed the 
Week 52 visit (placebo-controlled, double-blind treatment period) or withdrew from the 
study prior to Week 52. 
3.2
RATIONALE FOR STUDY DESIGN
3.2.1
Rationale for Study Population
The clinical hypothesis is most efficiently tested in early PD patients (H&Y Stage I or II), 
that are recently (2 years) diagnosed, and either de novo (untreated) or treated with a 
MAO-B inhibitor. Data from several previous treatment studies and longitudinal 
observational studies (Parkinson Study Group 2002, Parkinson Study Group PRECEPT 
Investigators 2007, Rascol et al 2011, NINDS Exploratory Trials in Parkinson Disease 
(NET-PD) FS-ZONE Investigators 2015, Simuni et al 2015) demonstrate that the 
progression rate in early PD patients measured using UPDRS or MDS-UPDRS is 
greater shortly after diagnosis and before the start of dopaminergic therapy 
(approximately 612 MDS-UPDRS total points/year without dopaminergic medication). 
The progression rate depends on baseline severity, study length, co-medication, and 
other factors. Several studies (both treatment and observational studies) have shown 
that it is feasible to enroll this early PD patient population in large, multicenter trials. The 
specificity of the diagnosis of Parkinson’s disease based on established clinical 
diagnostic criteria by trained movement disorder specialists will be further enhanced by 
including only patients with a dopaminergic deficit confirmed using DaT-SPECT.
The likelihood of starting dopaminergic treatment within one year after diagnosis in such 
a population is highly variable and a range between 14 and 50% of enrolled patients has
been reported (Parkinson Study Group 2002, Parkinson Study Group PRECEPT 
Investigators 2007, Rascol et al 2011, NINDS Exploratory Trials in Parkinson Disease 
(NET-PD) FS-ZONE Investigators 2015, Simuni et al 2015), depending on factors such 
as baseline severity, background therapy, study length and historical context. MAO-B 
inhibitor pre-treated patients have a reduced likelihood of starting dopaminergic therapy 
during the course of 12 months, while maintaining a relatively high progression rate 
(Parkinson Study Group 2002, Rascol et al 2011, NINDS Exploratory Trials in Parkinson 
Disease (NET-PD) FS-ZONE Investigators 2015). 

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After start of dopaminergic treatment (with continuous increases in levodopa doses and 
combination therapy with dopaminergic agonists), apparent progression rate is reduced
to a value corresponding to an MDS-UPDRS total change of 24 points/year 
(e.g., Parkinson Study Group 2004, NINDS Exploratory Trials in Parkinson Disease 
(NET-PD) FS-ZONE Investigators 2015), while variability (due to individual progression 
rate and patient response to dopaminergic treatment) remains high. Both rate of clinical 
progression and progression to variability ratio is best in an early patient population 
before start of dopaminergic treatment (6-12 MDS-UPDRS total points/year) (Parkinson 
Study Group 2002, Parkinson Study Group PRECEPT Investigators 2007, Rascol et al 
2011, NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators 
2015, Simuni et al 2015). 
Participants who initiate dopaminergic treatment in Part 1, Part 2 or Part 3 (levodopa or 
dopamine agonist) will continue in the study, as per their regular scheduled study visits 
and will continue to receive study drug. Initiation of dopaminergic treatment should take 
place during a regular scheduled study visit. Before initiation of dopaminergic treatment, 
patients are requested to perform all assessments of the “prior to start of dopaminergic 
treatment” visit as per SoA (Appendix 1). For participants who have started 
dopaminergic treatment (levodopa or dopamine agonist), the MDS-UPDRS and Digital 
Biomarker in-clinic assessments at subsequent visits will be performed in a practically-
defined “Off” state – no levodopa or dopamine agonist medication since the prior 
evening, including Part IV (motor assessment while on dopaminergic treatment), and the 
MDS-UPDRS Part III (motor assessment) will be repeated at least one hour after 
receiving their dopaminergic medication in the clinic (“On” state), along with Digital 
Biomarker in-clinic assessments. 
The effect on clinical progression rate determined using the MDS-UPDRS will be 
supported with a panel of exploratory biomarkers to assess the potential reduction of 
pathological changes and/or reduction of neuronal damage (e.g., reduction of loss of 
dopaminergic terminals measured using DaT-SPECT). In these early PD participants 
(within two years of diagnosis), there is already measurable loss of dopaminergic 
synaptic terminals in the striatum as documented using DaT-SPECT(de la Fuente-
Fernandez et al 2011, Nandhagopal et al 2011, Schwarz et al 2004). There is a high 
plausibility that disease progression can be slowed at this stage, while sufficient 
numbers of dopaminergic neurons and synapses (and other neuronal populations 
vulnerable to toxic -synuclein aggregates) are still present and available to be rescued 
by a disease-modifying treatment. Regardless of dopaminergic treatment, early PD 
patients show the fastest decrease of DaT-SPECT signal (i.e., loss of dopaminergic 
terminals) resulting in an inverse exponential decline in striatal DaT-SPECT uptake 
values (Nandhagopal et al 2011, Schwarz et al 2004).

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An empirical disease progression model based on data from the PPMI observational 
study (NCT01141023) was developed for patients not treated with symptomatic PD 
medication and patients on MAO-B inhibitors. The model was used to run clinical trial 
simulations that confirmed that the use of a mixed population (drug-naïve and on MAO-B 
inhibitor) is feasible and that more frequent assessments during the trial conduct may 
allow the detection of a disease-modifying effect.
3.2.2
Rationale for Control Group
This is the first POC study of RO7046015 in patients with PD, and information from other 
treatment and longitudinal studies (Parkinson Study Group 2002, Parkinson Study 
Group PRECEPT Investigators 2007, Rascol et al 2011, NINDS Exploratory Trials in 
Parkinson Disease (NET-PD) FS-ZONE Investigators 2015, Simuni et al 2015) was used 
to guide the current study design. In these studies, there was a high variability in the rate 
of disease progression depending upon factors such as population and study design, 
supporting the need for a placebo group in the current study. 
As the MDS-UPDRS primary endpoint is planned for after 52 weeks, the duration of the 
placebo treatment is limited to Part 1 (52 weeks), with the option to enroll participants 
already on stable MAO-B inhibitor at baseline and expected to receive stable MAO-B 
inhibitor throughout the study. In Part 2 and in Part 3, dopaminergic treatment may be 
initiated according to standard of care. Both PPMI (Marek et al 2011, Simuni et al 2015) 
and FS-Zone (NCT01280123; NINDS Exploratory Trials in Parkinson Disease (NET-PD) 
FS-ZONE Investigators 2015) studies, which included de novo and MAO-B 
inhibitor-treated early PD populations, effectively managed early PD for 6 months to a 
year, without requiring dopaminergic treatment. 
3.2.3
Rationale for Dosage Selection
Currently, there is no biomarker available to measure target engagement in the CNS, 
either directly or indirectly, in humans. As anticipated from non-clinical data, there were 
no effects on free -synuclein in the CSF at IV doses administered up to 60 mg/kg in 
patients (MAD study, PRX002-CL002), while a dose-dependent reduction of free 
-synuclein in serum of up to 97% was observed. Based on monkey PK/PD studies and 
modelling work that took into consideration the estimated brain penetration of 
RO7046015 and the binding of the antibody to monomeric -synuclein (the predominant 
form in CSF), it was expected that there would be no effect on free -synuclein in CSF 
measurable at the doses investigated in the SAD and MAD studies (PRX002-CL001 and 
PRX002-CL002, see RO7046015 Investigator's Brochure). Therefore, human PK/PD 
information obtained from the SAD and MAD studies cannot be used to guide efficacy 
dose selection in patients. 

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The dose-selection is guided by the in vivo animal pharmacology studies. In the 
dose-response study in the transgenic mouse model Line 61, effects on 
histopathological endpoints were seen at weekly IP doses of 1 mg/kg and higher. Effects 
on functional endpoints were seen at 1 mg/kg (spatial learning assessment) or at higher 
doses of at least 10 mg/kg (restoration of gait/balance impairment). A dose of 60 mg/kg 
every 4 weeks in patients with PD in the MAD study (PRX002-CL002) achieved average 
trough serum concentrations in the range of those observed after 10 mg/kg weekly IP 
dose in the transgenic mouse model (approximately 70 g/mL) while the dose of 
10 mg/kg Q4W in patients achieved mean trough concentrations above those observed 
after 1 mg/kg in mice (approximately 17 g/mL). 
RO7046015 was well tolerated without any reports of treatment-emergent SAEs. The 
most frequently reported mild to moderate treatment-emergent adverse events (TEAEs) 
in the MAD study in PD patients (PRX002-CL002) included constipation (9.1%), infusion-
related reactions (IRRs) (7.3%), diarrhea (5.5%), peripheral edema (5.5%) and 
post-lumbar puncture syndrome (5.5%). Mild to moderate IRRs, that all resolved were 
limited to the 60 mg/kg dose cohort and were observed in 4 of 12 treated patients. 
Based on previous experience with other mAbs, it is expected that participants can 
safely be treated with such high doses provided certain measures are taken to minimize 
the risk for IRRs (see Section 4.4.2).
The exposure at the NOAEL in cynomolgus monkey was 6 times (Cmax) and 5 times 
(AUC over 4 weeks) higher than the exposure achieved with 60 mg/kg in the MAD study, 
which is considered an acceptable safety window. 
Since there is uncertainty around translatability of animal to man in this disease, it is 
recommended to use the maximal tolerable and/or achievable dose (e.g., 60 mg/kg) and 
a second dose that produces exposure levels that are well separated from the high dose 
while achieving trough levels at least as high as those observed in the mouse model at 
1 mg/kg. Therefore, a second dose in patients equal to or greater than 10 mg/kg is 
appropriate as low dose.
The PK in humans is well described by a population PK model in the dose range of 
0.3-60 mg/kg for single and multiple IV dosing from the SAD and MAD studies 
(PRX002-CL001 and PRX002-CL002). The PK is similar in healthy subjects and patients 
and exposure increases dose-proportionally (see RO7046015 Investigator's Brochure).
Body weight has an effect on clearance (and volume of distribution) such that exposure 
increases in patients with lower body weight. A switch to more convenient flat dosing is 
possible to achieve similar exposures across a large range of body weight provided the 
use of an approximately 25% lower dose in participants with lower body weight (65 kg) 
is implemented at high doses where there is an increased risk for IRRs.

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Therefore, two doses were selected to match approximately the exposure achieved with 
60 mg/kg and a lower dose that achieves exposures at least as high as with 10 mg/kg 
and which leads to approximately 30% overlap of trough levels. The high-dose is 
4500 mg for participants with body weight equal or higher than 65 kg or 3500 mg for 
participants with body weight lower than 65 kg), and the low-dose is 1500 mg 
(independent of the participant’s body weight), given IV (Q4W). Additional information 
can be found the RO7046015 Investigator's Brochure. As described in Section 3.1.2.1, 
results of pre-specified safety interim analyses may lead to a stop of enrollment to the 
highest dose cohort and introduction of a new mid-dose cohort of 3000 mg 
(corresponding to a median AUC of approx. 112800 g h/mL and a median Cmax of 
approx. 700 g/mL, close to the values observed with the 30 mg/kg dose in the MAD 
study PRX002-CL002). 
Part 1 results may guide Phase III study dose selection. Once identified (and if 
applicable), participants will be switched to this dose in Part 3 (see Section 3.1.1.3 for 
further details). This dose will not exceed the high dose tested in the present BP 39529 
study.
3.2.4
Rationale for Duration of Treatment
Based on data from observational cohorts such as the PPMI study and previous 
placebo-controlled treatment trials (see Section 3.2.1), a 52-week treatment duration is 
expected to be sufficient to demonstrate between group differences due to the effects of 
a disease-modifying treatment that changes the rate of progression in early stage PD 
patients without dopaminergic treatment. See Section 3.2.5 for the rationale for the 
one-year extension and Section 3.2.6 for the rationale for the five-year extension. 
3.2.5
Rationale for One-Year Extension (Part 2)
Participants who complete the double-blind, placebo-controlled treatment period (Part 1) 
will continue in an all-participants-on-treatment (RO7046015), blinded to dose extension 
for an additional 52 weeks (Part 2). See Section 3.1.1.2 for further information. This will 
allow collection of safety information on long-term exposure with RO7046015, as well as 
concomitant dopaminergic treatment.
The clinical and biomarker outcomes described in Sections 2.2 and 3.3.4 will also be 
evaluated over a period of up to 104 weeks (Part 1 and Part 2) using a disease 
progression model that will consider start of RO7046015 treatment, start of 
dopaminergic treatment and baseline severity to assess the effects of RO7046015 
beyond one year of treatment and to identify potential parameters that are sensitive to 
RO7046015 treatment after start of dopaminergic treatment (see Section 6.7 and 6.8).
The doses of RO7046015 in Part 2 (52-week extension) will be the same as in Part 1. 
Participants randomized to RO7046015 in Part 1 will remain on the same dose, while 
participants randomized to placebo will be re-randomized at the start of Part 2 to one of 
the two active doses of RO7046015 with a 1:1 allocation ratio.

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3.2.6
Rationale for Five-Year Extension (Part 3)
Participants who complete the blinded to dose extension (Part 2) will be offered 
participation in an all-participants-on-treatment extension (RO7046015) for an 
additional five years (Part 3), see Section 3.1.1.3 for further information. This will 
allow collection of safety and efficacy information on long-term exposure to RO7046015, 
as well as concomitant dopaminergic treatment.
Until the Phase III study dose is identified, participants will remain on the same dose 
they were assigned to in Part 2. Once identified (and if applicable), participants will be 
switched to the Phase III study dose as described in Section 3.1.1.3. 
3.2.7
Rationale for Biomarkers and Digital Assessments
3.2.7.1
DaT-SPECT
A striatal dopamine transporter deficit on dopamine transporter imaging by DaT-SPECT 
currently represents the most established imaging marker in de novo PD, reflecting 
neurodegeneration in key brain regions affected by -synuclein pathology. Indeed, 
longitudinal studies in PD patients have established an inverse exponential decline in 
striatal DaT-SPECT uptake values over time, i.e., with disease progression 
(Nandhagopal et al 2011, Schwarz et al 2004). Therefore, in PD, DaT-SPECT will be 
used as a secondary outcome measure to determine whether RO7046015 has an effect 
on the underlying pathology of PD. 
3.2.7.2
Magnetic Resonance Imaging
Three different types of MRI will be explored in this study, in order to assess different 
aspects of brain function and integrity that have been proposed to be impacted by PD 
pathology (grey and white matter integrity, functional interaction between different brain 
regions and metabolic cost associated with brain function). At the end of Part 2 (if 
applicable) and in Part 3, iron and neuromelanin-sensitive (NM) imaging will be added 
to the MRI battery. Please note that the MRI sequences will only be acquired if the 
investigative sites have the required scanner software/sequences capabilities.
Diffusion Tensor Imaging
DTI is an MRI sequence which can be used to assess grey and white matter integrity in 
the brain. In-house analyses of the PPMI whole-brain DTI data (Taylor et al, 2018), as 
well as a published report (Zhang et al 2016), demonstrated significant annual 
reductions in DTI-based measures of white matter integrity in PD compared to healthy 
control participants. Importantly, these changes significantly correlated with declining 
CSF -synuclein levels (Zhang et al 2016), supporting the use of DTI as a downstream 
measure of progressive -synuclein pathology (Burke and O’Malley 2013). 

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Resting State Functional MRI 
Rs-fMRI provides a measure of functional brain network integrity, i.e., the ability of brain 
regions to interact with one another to enable thinking (Prodoehl et al 2014). Resting 
state functional connectivity analyses demonstrated that functional connectivity declines 
significantly over time in PD, independent of age effects (Olde Dubbelink et al 2014). 
Moreover, the magnitude of resting state functional connectivity over one year correlated 
significantly with decline in motor performance as measured by the MDS-UPDRS Part III 
motor scale (Dukart et al 2017, Manza et al 2016). The present study will therefore 
acquire rs-fMRI to perform striatal functional connectivity analyses testing for effects of 
RO7046015 treatment.
Arterial Spin Labeling
2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography (FDG-PET) has 
traditionally been used to assess metabolic cost associated with brain function, but it is 
an expensive and invasive procedure. Cerebral blood flow (CBF) provides another good 
approximation of metabolic cost associated with brain function. MRI ASL is a less 
expensive and non-invasive method to estimate CBF than FDG-PET (Teune et al 2014), 
and has recently reached a high level of multi-site standardization (Alsop et al 2015, 
Mutsaerts et al 2015). Whole-brain CBF patterns are disturbed in PD, and the degree of 
disturbance increases with time (e.g., Wu et al 2013). Therefore, the present study will 
examine participants with MRI ASL to compare changes in CBF patterns between the 
treatment groups.
Neuromelanin-sensitive MRI
NM sequesters metal ions are a product of dopamine metabolism. NM is enriched in the 
substantia nigra and considered a marker of nigral integrity in PD patients. In NM-
MRI of Parkinson’s patients, a loss of pigments has been repeatedly observed. 
Sensitivity and specificity for PD diagnosis was confirmed in a meta-analysis (Wang et 
al 2019). Further studies have demonstrated longitudinal decline in substantia nigra 
pars compacta contrast ratio (Matsuura et al 2016) and substantia nigra volume 
(Gaurav et al 2018). The present study will therefore examine treatment-specific 
slowing of substantia nigra NM loss in Parkinson’s Disease patients.
Iron imaging
Iron accumulation in the brain leads to toxic reactive oxygen species and can trigger 
the aggregation of alpha synuclein (Wan et al 2017). In Parkinson’s Disease, iron has 
consistently been shown to be increased relative to healthy controls, based on 
pathological and MRI studies (Wang et al 2016). In addition, longitudinal studies have 
shown a PD-specific increase in substantia nigra brain iron (Du et al 2018) which was 
correlated to clinical changes during the same time frame (Ulla et al 2013). The present 
study will therefore examine treatment-specific slowing of iron accumulation in the 
brain MRI in Parkinson’s Disease patients.

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3.2.7.3
Digital Biomarkers
Smartphones and wrist-worn wearables have high quality sensors that enable the 
remote, non-invasive, frequent and precise measurement of motor and non-motor
symptoms (Maetzler et al 2013, Ossig et al 2016). These digital biomarkers may 
therefore provide more sensitive assessments of symptom progression and fluctuation 
over time than established clinical rating scales. Smartphone sensor data, including 
motion and location, were collected during the previous RO7046015 MAD study 
(PRX002-CL002), where patients completed daily “active tests” and then carried the 
phone with them throughout the day (“Passive Monitoring”), revealing very high 
acceptance and adherence and excellent correspondence with clinical measures of 
motor symptom severity (i.e., MDS-UPDRS III) (Lipsmeier et al 2018), similar to previous
reports (e.g., Tsanas et al 2010, Kostikis et al 2014, Patel et al 2011, Kassavetis et al 
2016). This digital biomarker approach will therefore be implemented in the current study 
to maximize the probability of detecting a potential therapeutic effect of RO7046015 and 
to potentially provide new insights into subject functioning and behavior.
3.2.7.4
Clinical Genotyping
Dissection of the genetic architecture of a complex disorder such as PD is important to 
understand its biological basis, assess the individual predisposition of disease, and 
evaluate the capacity of therapeutic interventions.
3.2.7.5
Cerebrospinal Fluid Biomarkers
Molecular changes that take place in the CNS can be mirrored in CSF as an accessible 
source of brain-derived proteins. Efforts together with Public Private Partnerships 
(e.g., the Michael J Fox Foundation) are ongoing to identify and validate CSF 
biomarkers that reflect disease severity, its progression and/or to serve as downstream 
markers of -synuclein pathology. CSF biomarkers will be measured in patients who 
consent to an optional lumbar puncture. A matching serum sample will be collected in 
Part 1 and Part 2, matching serum and plasma samples will be collected in Part 3. See 
SoA (Appendix 1, Appendix 2 and Appendix 3) for the timing of CSF sampling. 
3.2.7.6
Skin Biopsy and Collection of Screen Failure Data and 
Samples
No biomarker tools currently exist to detect and monitor aggregated -synuclein in brain 
in vivo, and the definitive diagnosis can only be made post-mortem through 
neuropathology (Dickson et al 2009). However, Donadio et al (2014) recently reported 
that pathological forms of -synuclein were detectable in the accessible peripheral 
neurons of skin biopsy samples obtained from PD patients, and a cross-sectional study 
indicated that the degree of peripheral nerve pathology was associated with disease 
severity (Wang et al 2013). Longitudinal skin biopsy sampling will therefore be 
implemented for the direct and in vivo assessment of -synuclein pathology and its 
progression and response to therapy. Clinical data and samples, including skin biopsies, 
will be collected from DaT-SPECT negative screen failure participants to determine 

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whether the detection of -synuclein skin pathology may be used as a sensitive and 
specific, less invasive, tool to diagnose PD.
3.3
OUTCOME MEASURES
3.3.1
Safety Outcome Measures
The safety outcome measures for this study are as follows:

Changes in safety laboratory tests (hematology, chemistry and coagulation) from 
baseline over time.

Incidence of treatment-emergent abnormal laboratory values and abnormal 
laboratory values reported as AEs.

Incidence and severity of AEs.

Incidence of ADAs.

Changes in ECG assessments from baseline over time; incidence of abnormal ECG 
assessments.

Change in blood pressure (BP [systolic and diastolic], heart rate, and orthostatic 
measurement from baseline over time, incidence of abnormal blood pressure 
[systolic and diastolic], heart rate, and orthostatic changes).

Incidence of exacerbation of motor and psychiatric side-effects (including C-SSRS).

Incidence of MRI abnormalities.
3.3.2
Pharmacokinetic Outcome Measures
The PK outcome measures for this study are as follows:

Population and individual primary PK parameter estimations (e.g., clearance and 
volume of distribution) and the influence of various covariates on these parameters.

Secondary PK parameters (e.g., AUC, Ctrough) derived from the individual post-hoc 
predictions.
3.3.3
Efficacy Outcome Measures
The primary efficacy outcome measure for this study is as follows:

Change in total MDS-UPDRS score (sum of Parts I, II and III) from baseline at Week 
52.
The secondary efficacy outcome measures for this study (after 52 weeks of treatment 
with RO7046015 or placebo) are as follows:

Change from baseline in MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part 
III total and Part III subscores 

Change from baseline in DaT-SPECT in ipsilateral (to the clinically dominant side) 
putamen binding ratio values

Change from baseline in MoCA total score 

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
Change from baseline in Clinical Global Impression of Improvement (CGI-I) 

Change from baseline in Patient Global Impression of Change (PGIC) 

Change from baseline in Schwab and England Activities of Daily Living (SE-ADL) 

Time to worsening of motor or non-motor symptoms as measured by MDS-UPDRS 

Time to start of dopaminergic PD treatment (levodopa or dopamine agonists)
3.3.4
Exploratory Outcome Measures
The exploratory outcome measures for this study are change from baseline to Week 52,
to Week 104 and to Part 3 Week 260 in:

MDS-UPDRS Part III total and Part III subscores central vs local ratings for 
consistency and accuracy

Time to worsening of motor or non-motor symptoms as measured by MDS-UPDRS 
or starting dopaminergic treatment (levodopa or dopamine agonist) 

Modified Hoehn & Yahr (mH&Y).

PDSS-2 total score and sub-scales.

SCOPA-AUT total score and subdomain scores.

PDQ-39 total score and sub-scales

Digital Biomarkers and patient-reported outcomes (Smartphone and wrist-worn 
wearable assessments):
–
Diary questions (patient reported outcome [PRO]).
–
PAC-SYM questionnaire (PRO).
–
Hospital Anxiety and Depression Scale (HADS) total score and sub-scales: 
anxiety (HADS-A), and depression (HADS-D) (PRO).
–
EQ-5D-5L questionnaire (PRO).
–
Sensor data collected during “Active Tests”, assessing motor symptoms (upper 
and lower body movement, upper limb dexterity, voice/speech) and non-motor 
symptoms - including an electronic Symbol Digital Modalities Test (eSDMT) to 
measure attention and executive function.
–
Sensor data collected during “Passive Monitoring” assessing activity, 
movement and motor symptoms associated with routine daily living.
–
Sensor data collected during “In-Clinic Assessments”, including the Timed Up 
and Go Test and selected items from the Berg Balance Scale.

Serum, plasma, and CSF biomarkers related to Parkinson’s disease (CSF in 
consented patients only).

-synuclein pathology in peripheral nerves (skin biopsies in eligible participants; see 
exclusion criteria in Section 4.2.3).

DaT-SPECT binding ratio values for: striatum, caudate and putamen (average
ipsilateral and contralateral)

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
DTI MRI for mean diffusivity and fractional anisotropy.

rs-fMRI for functional brain connectivity.

ASL MRI for cerebral blood flow.

NM-MRI for substantia nigra integrity.

Iron imaging for brain iron accumulation.

Time to start or change of co-medication for non-motor symptoms that may be 
related to PD (cognition, constipation, depression, anxiety, excessive daytime sleep, 
nocturnal sleep, urogenital symptoms/sexual dysfunction).

Start or change of co-medication for non-motor symptoms that may be related to 
imaging biomarkers (DAT Scan and ASL).

Parkinson-related effects on the loss of autonomic tone as measured by heart rate 
variability. 

Composite score of MDS-UPDRS Part II (patient reported motor experiences of 
daily living) and MDS-UPDRS Part III (clinician rated motor signs of PD) sub-
items.

MDS-UPDRS Part IV at Week 52, at Week 104 and Part 3 Week 260 in participants
who started dopaminergic treatment (levodopa or dopamine agonist).
4.
MATERIALS AND METHODS
4.1
CENTER
This is a multicenter study (approximately 60 centers) to be conducted in multiple 
countries worldwide. Additional site(s) may be included for back-up purposes and may 
be activated if needed.
4.2
STUDY POPULATION
4.2.1
Recruitment Procedures 
Participants will be identified for potential recruitment per site-specific recruitment plans 
prior to consenting to take part in this study. Any recruitment materials for participants
will receive Institutional Review Board or Ethics Committee (IRB/EC) approval prior to 
use.
4.2.2
Inclusion Criteria
Participants must meet the following criteria for study entry:
1.
Idiopathic PD with bradykinesia plus one of the other cardinal signs of PD (resting 
tremor, rigidity) being present, without any other known or suspected cause of PD 
untreated or treated with MAO-B inhibitor.
2.
Male or female, 40 to 80 years of age, body weight range of 45 kg/99 lbs 
to 110 kg/242 lbs and a body mass index (BMI) of 18 to 34 kg/m2.
3.
A diagnosis of PD for 2 years or less at screening.
4.
H&Y Stage I or II.

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5.
A screening brain DaT-SPECT consistent with PD (central reading).
6.
Clinical status does not require dopaminergic PD medication and is not expected to 
require dopaminergic treatment within 52 weeks from baseline.
7.
If presently being treated for PD, a stable dose of MAO-B inhibitor (rasagiline or 
selegiline) for at least 90 days prior to baseline and not expected to change within 
52 weeks. 
8.
Able and willing to provide written informed consent and to comply with the study 
protocol according to ICH and local regulations.
9.
For women of childbearing potential: use of highly effective contraceptive methods 
(that result in a failure rate of1% per year) during the treatment period and for at 
least 30 days (or longer if required by local regulations) after the last dose of study 
drug. 
A woman is considered to be of childbearing potential if she is post-menarcheal, has 
not reached a post-menopausal state (12 continuous months of amenorrhea with 
no identified cause other than menopause), and has not undergone surgical 
sterilization (removal of ovaries and/or uterus).
Examples of highly effective contraceptive methods (with a failure rate of 1% per 
year) include bilateral tubal ligation, vasectomized partner, established, proper use 
of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine 
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient. Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.
10. For men: use of contraceptive measures as defined below:
With female partners of childbearing potential or pregnant female partners, men 
must use a condom during the treatment period and for at least 30 days (or longer if 
required by local regulations) after the last dose of study drug to avoid exposing the 
embryo. Men must refrain from donating sperm during this same period. The female 
partners should use a contraception method with a failure rate of 1% per year 
during the treatment period and for at least 30 days (or longer if required by local 
regulations) after the last dose of study drug.
The reliability of sexual abstinence should be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the patient. Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.

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4.2.3
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from study entry:
Current or Past Medical History
1.
Medical history indicating a Parkinson syndrome other than idiopathic PD, including 
but not limited to, progressive supranuclear gaze palsy, multiple system atrophy, 
drug-induced parkinsonism, essential tremor, primary dystonia.
2.
Known carriers of certain familial PD genes (Parkin, PINK1, DJ1). Note: GBA, 
synuclein, LRRK2 mutation carriers are allowed.
3.
History of PD-related freezing episodes or falls.
4.
A diagnosis of a significant CNS disease other than Parkinson’s disease (including 
but not limited to Huntington’s disease, normal pressure hydrocephalus, 
cerebrovascular disease including stroke, fronto-temporal dementia, Alzheimer’s 
disease); history of repeated head injury; history of epilepsy or seizure disorder 
other than febrile seizures as a child. 
5.
Mini Mental State Examination (MMSE) 25. 
6.
Reside in a nursing home or assisted care facility.
7.
History of or screening brain MRI scan indicative of clinically significant abnormality 
including, but not limited to, prior hemorrhage or infarct 1 cm3, 3 lacunar infarcts.
8.
Concomitant disease or condition within six months of screening, or as specified 
below, that could interfere with, or treatment of which might interfere with, the 
conduct of the study, or that would, in the opinion of the Investigator, pose an 
unacceptable risk to the participant in this study or interfere with the participant’s 
ability to comply with study procedures or abide by study restrictions, or with the 
ability to interpret safety data, including, but not limited to:
a.
Autoimmune disease (however, well controlled conditions such as, but not 
limited to, quiescent rheumatoid arthritis (RAS), controlled type I diabetes, or 
mild-to-moderate psoriasis not requiring systemic medications may be 
acceptable after discussion with Sponsor/Medical monitors).
b.
A history of cancer within 5 years of baseline with the exception of fully 
excised non-melanoma skin cancers or non-metastatic prostate cancer that 
has been stable for at least 6 months.
c.
Any active infectious disease at baseline.
d.
Current, or history of, alcohol or drug abuse or other dependence (except 
nicotine dependence) within two years before screening.
e.
Any febrile illness within one week prior to first dose administration.
f.
Any current psychiatric diagnosis according to Diagnostic and Statistical 
Manual of Mental Disorders fifth edition (DSM-5), International Statistical 
Classification of Diseases and Related Health Problems 10th Revision (ICD-
10) or equivalent, that may interfere with the participant’s ability to perform the 

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study and all assessments (e.g., major depression, mental retardation, 
schizophrenia, bipolar disorder, etc.). Note: Mild depression, depressive mood 
or mild anxiety arising in the context of PD, are not exclusionary. 
9.
The following cardiovascular conditions:
a.
Myocardial infarction within 12 months of baseline.
b.
Known history or documentation of uncontrolled hypotension or bradycardia 
on more than one occasion within three months prior to baseline.
c.
Known history or documentation of uncontrolled hypertension on more than 
one occasion within three months prior to baseline.
d.
Resting pulse rate (PR) greater than 100 or less than 45 bpm.
e.
Clinically significant cardiovascular disease including any of the following: 
unstable angina, decompensated congestive heart failure, clinically significant 
arrhythmias or symptomatic orthostatic hypotension.
f.
A corrected QT (QTcF) interval measurement 450 ms for males or 470ms 
for females at screening, or a family history of long QT syndrome
g.
Intermittent second or third degree atrioventricular (AV) heart block or AV 
dissociation is excluded (asymptomatic patients with first degree AV block 
may be included).
10. Clinically significant abnormalities in laboratory test results at the Screening visit, 
including hepatic and renal panels, complete blood count, chemistry panel and 
urinalysis, including:
a.
Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) 2 times the upper limit of normal (ULN).
b.
Serum creatinine > 1.5 times the ULN.
c.
Hematocrit (Hct) less than 35% for males and less than 32% for females, or 
absolute neutrophil cell count of 1500/L (with the exception of a 
documented history of a chronic benign neutropenia), or platelet cell count 
of 120,000/L; international normalized ratio (INR) 1.4 (in patients not on 
anticoagulants) or other coagulopathy.
d.
A clinically significant abnormal thyroid-stimulating hormone (TSH) test.
e.
A positive urine drug screen for a drug of abuse.

For participants treated with selegiline, the amphetamine drug abuse test 
should be based on the results from a urine assay by liquid 
chromatography-mass spectrometry which is able to differentiate “false 
positive methamphetamine” from “true positive methamphetamine”.

For participants treated with benzodiazepines: a positive urine drug 
screen for benzodiazepines is allowed, provided that the prescription has 
been stable for 90 days prior to baseline (refer to exclusion criterion 15). 
f.
Positive result for acute or chronic infectious hepatitis B (HBV; [i.e., HBsAg 
positive test]), for hepatitis C (HCV), or HIV 1 or 2. Successfully treated HCV 
patients (undetectable HCV RNA) are eligible for enrollment. Participants who 
are immune due to HBV natural infection or HBV vaccination are eligible.
g.
For women of childbearing potential, a positive urine or blood pregnancy test.

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11. Lactating women.
Medications and treatments
12. Prior treatment with dopaminergic medication (e.g., levodopa or a dopaminergic 
agonist) with no clinical treatment response or a clinical treatment response 
inconsistent with PD (e.g., absence of observable response to a sufficiently high-
dose of levodopa [i.e., 600 mg/day]).
13. Use of any of the following: catechol-O-methyl transferase (COMT) inhibitors 
(entacapone, tolcapone), amantadine or anticholinergics, or dopaminergic 
medication (levodopa and both ergot and non-ergot [pramipexole, ropinirole, 
rotigotine] dopamine agonists) for more than a total of 60 days or within 60 days of 
baseline.
14. Anti-epileptic medication for non-seizure-related treatment which has not remained 
stable for at least 60 days prior to baseline.
15. Anti-depressant or anxiolytic use that has not remained stable for at least 90 days 
prior to baseline. The use of fluoxetine and fluvoxamine is not permitted. For 
patients treated with an MAO-B inhibitor and an antidepressant (except fluoxetine 
and fluvoxamine), a 6-month period of stable and tolerated dosing before baseline is 
required.
16. Use of any of the following medications within 90 days prior to baseline; 
antipsychotics (including clozapine and olanzapine), metoclopramide, alpha 
methyldopa, flunarizine, amoxapine, amphetamine derivatives, reserpine, bupropion, 
buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, 
phentermine, phenylpropanolamine, and modafinil. 
17. Participated in an investigational drug, device, surgical, or stem cell study in PD.
18. Any prior treatment with an investigational PD-related vaccine (including active 
immunization or passive immunotherapy with monoclonal antibodies). 
19. Prior participation in any RO7046015 or PRX002 study.
20. Receipt of any non-PD investigational product or device, or participation in a non-PD 
drug research study within a period of 30 days (or 5 half-lives of the drug, whichever 
is longer) before baseline.
21. Receipt of any monoclonal antibody or investigational immunomodulator within 
180 days (or 5 half-lives, whichever is longer) before baseline (e.g., monoclonal 
antibodies, intravenous immunoglobulin [IVIG], interleukin 2 [IL-2], interleukin 12 
[IL-12], interferon or immunosuppressive drugs).
22. Immunomodulating drugs within 30 days prior to baseline.
23. Allergy to any of the components of RO7046015 such as citrate, trehalose and 
polysorbate (Tween) 20 or a known hypersensitivity or an IRR to the administration 
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Procedural
24. Any contraindications to obtaining a brain MRI (e.g., claustrophobia unresponsive to 
reassurance or low dose of an anxiolytic agent, tooth implants) and any 
contraindications to obtain a DaT-SPECT (i.e., known hypersensitivity to the active 
substance or to any of the excipients). Patients with a hypersensitivity to iodine may 
receive an alternative thyroid blocking agent (e.g., potassium perchlorate or sodium 
perchlorate).
25. For participants consenting to provide optional CSF samples by lumbar puncture 
(LP): LP will only be performed if the participant does not have any contraindication 
to undergoing an LP including, but not limited to: INR 1.4 or other coagulopathy, 
platelet cell count of 120,000/L, infection at the desired LP site, taking 
anti-coagulant medication within 90 days of baseline (Note: low dose aspirin 
(acetylsalicylic acid [ASA] is permitted), severe degenerative arthritis of the lumbar 
spine, suspected non-communicating hydrocephalus or intracranial mass, prior 
history of spinal mass or trauma is/are identified. Participants failing to meet these 
criteria can still participate in the study and all other study assessments (with the 
exception of LP) as appropriate. Participants could be excluded from the study if the 
CSF has more than 5 WBCs/mm3 (according to local laboratory assessment). This
should be discussed with the Medical Monitor (e.g., if there is evidence that the 
spinal tap was traumatic, the participant may still be considered for study eligibility).
26. For skin biopsy at the cervical paravertebral region:
Condition that either precludes the safe performance of the skin punch biopsy or 
may interfere with obtaining evaluable skin tissue biopsies, including any previous 
or active significant dermatological disease (e.g., previous biopsy with any of the 
following findings: inflammatory disease, scar tissue, psoriasis, keloid formation, 
skin cancer).
Participants failing to meet these criteria can still participate in the study and all 
other study assessments (with the exception of skin biopsy) as appropriate.
27. Donation of blood over 500 mL within three months prior to screening.
4.3
METHOD OF TREATMENT ASSIGNMENT AND BLINDING
Randomization will be done via an Interactive Web Response System (IWRS) or an 
equivalent method (IxRS). Patients can only be randomized once all screening 
assessments have been completed and eligibility confirmed.
In Part 1, participants will be randomized to placebo, or one of the two active treatment 
doses: 4500 mg (3500 mg in participants with body weight lower than 65 kg) and 
1500 mg with a 1:1:1 allocation ratio, see Section 3.1.1.1. 
For Part 2, participants who complete the initial placebo-controlled part will switch into 
the extension, in which case, a re-randomization will take place using the rules 
described in Section 3.1.1.2. Although only placebo patients will be re-randomized at the 
start of Part 2, all patients will be registered in IxRS at the start of Part 2 to ensure the 
blind is maintained.

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For Part 3, participants will remain at the same dose they received in Part 2 until the 
Phase III study dose is identified. Once identified and if applicable, participants will be 
switched to the Phase III study dose as described in Section 3.1.1.3. All patients will be 
registered in IxRS at the start of Part 3 to keep track of the study period. Also the IxRS 
will record the date in which the patients switched to the Phase III dose.
The randomization list will be generated by the IxRS provider. The list will be provided to 
statisticians, and/or programmers, and/or other specialists external to Roche as needed 
to create unblinded data displays for the iDMC reviews (see Section 3.1.2). Members of 
the iDMC will be fully unblinded; no Roche personnel will have access to the unblinded 
data displays reviewed by the iDMC.
Treatment assignment for Part 1 will only be made available to the Sponsor personnel 
analyzing and interpreting the data from the placebo-controlled period (after completion 
of Part 1 of the study). However, site personnel and participants will remain blinded 
throughout the study, including Part 2 and Part 3. Once Phase III study dose is 
identified, site personnel and participants will be informed of that dose. 
The randomization list will also be made available to the pharmacist preparing the study 
treatment (for the corresponding study center only) to the individuals responsible for PK 
and ADA sample bioanalysis and to other study personnel as described in a separate 
document (List of Unblinded Site Members and Unblinded Non-Site Members).
If unblinding is necessary for patient management (in the case of a serious adverse 
event), the Investigator and the Sponsor will be able to break the treatment code by 
contacting the IxRS. Treatment codes should not be broken except in emergency 
situations. If possible, the responsible Scientific Leader/Medical Monitor should be 
contacted before the code is broken.
If the Investigator wishes to know the identity of the study drug for any other reason, he 
or she should contact the Medical Monitor. The Investigator should document and 
provide an explanation for any premature unblinding (e.g., accidental unblinding, 
unblinding due to a serious adverse event).
As per Health Authority reporting requirements, the Sponsor will break the treatment 
code for all unexpected serious adverse events (see Section 5.1) that are considered by 
the Investigator to be related to study drug. All such occurrences must be documented in 
the study file. 
Whenever disclosure of the identity of the test medication is necessary, adequate 
procedures will be in place to ensure integrity of the data. Any unblinding at the 
investigating site will be documented in the study report with date, reason for identifying 
the drug and the name of all the person(s) who requested the unblinding.

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4.4
STUDY TREATMENT
4.4.1
Formulation, Packaging, and Handling of RO7046015
The investigational medicinal product (IMP) in this study is RO7046015 for IV infusion, 
which needs to be prepared locally. Placebo formulation will not be provided; patients 
randomized to placebo will receive an IV infusion of normal saline (provided by the sites). 
Symptomatic/dopaminergic PD medication and premedication before infusion are 
considered non-investigational medicinal products (NIMPs). 
RO7046015 drug product is supplied as a concentrate for solution for infusion of 500 mg 
in a 10-mL glass vial with elastomeric stopper and aluminum seal.
Prior to use, the appropriate volume of RO7046015 solution for infusion should then be 
added to normal saline (after removal of the same amount of saline from the bag) by the 
unblinded study pharmacist who is uninvolved in any other aspects of the study, for IV 
administration to participants in the clinical study. Placebo will be prepared using the 
same type of infusion bag and tubing that will be used for the active RO7046015. All 
infusion kits will be blinded to other site staff, as described in the Pharmacy Manual.
Study drug packaging will be overseen by the Roche clinical trial supplies department 
and bear a label with the identification required by local law, the protocol number, drug 
identification and strength.
The packaging and labeling of the study medication will be in accordance with Roche 
standard and local regulations.
RO7046015 vials should be stored at 2–8C until use. For further details, see the 
RO7046015 Investigator’s Brochure.

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4.4.2
Dosage, Administration and Compliance
RO7046015 study drug product 50 mg/mL (supply vials 500 mg/10 mL) will be 
administered IV after dilution in 250 mL 0.9% NaCl bags. The qualified individual 
(unblinded study pharmacist) responsible for dispensing the study drug at the site will 
prepare the correct dose according to the randomization schedule. This individual will 
write the date dispensed and participant’s number on the study drug box label and on 
the Drug Inventory/Dispensing Log. This individual will also record the study drug 
(e.g., batch number) received by each patient during the study.
Premedication in Part 1 and Part 2
In vitro studies have characterized RO7046015 as having a low potential for induction of 
cytokine release (RO7046015 Investigator Brochure). A premedication regimen will be 
administered 30-60 min prior to infusion for the first three doses in Part 1 and first three 
doses in Part 2 of the study. The premedication regimen will consist of the following: 

Loratadine 10 mg by mouth (PO). In countries or sites where loratadine is not 
readily available, the following alternatives are acceptable in the preferred order:
–
Desloratadine 5 mg PO
–
Cetirizine 10 mg PO
–
Other alternatives may be considered acceptable upon consultation with the 
Sponsor/Medical Monitor.
AND

acetaminophen 650 mg PO (or minimum recommended adult dose of paracetamol 
as per local regulation).
Premedication in Part 3
In Part 3, no systematic premedication is required for the three first doses; 
premedication is based on signs and symptoms at previous infusion. Thus, participants 
who experienced a Grade 2 or higher IRR on a previous infusion should be pre-
medicated for subsequent infusion with:

an antihistamine (H1-receptor antagonist), anti-pyretics (acetaminophen 500-
1000 mg PO/IV or alternatively ibuprofen 400-600 mg or other NSAIDs per 
institutional standard if acetaminophen cannot be tolerated). 
If a participant experienced a Grade 3 IRR, the same as above should apply and 200 mg 
hydrocortisone IV (or equivalent dose of another corticosteroid) is recommended to be 
added. 
Premedication regimens for subsequent cycles may be reduced or omitted in case of ≤
Grade 1 events in the previous cycle.

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Premedication in case of IRR recurrence in Part 3
In case of recurrent IRRs (irrespective of grading) the premedication regimen will 
consist of the following:

a dose of an antihistamine (H1-receptor antagonist, as per local practice) is taken 
the night before the administration
AND

the same dose of the same antihistamine (H1-receptor antagonist), with an anti-
pyretics (acetaminophen 500-1000 mg PO/IV or alternatively ibuprofen 400-600 
mg or other NSAIDs per institutional standard if acetaminophen cannot be 
tolerated) are taken 1-2 hours before infusion. 

Addition of steroids may be considered in case of previous Gr 3 IRR.
Study Drug Administration
Study drug must be administered in a setting where full emergency resuscitation 
capabilities/facilities are immediately available and participants are under close 
supervision of the Investigator at all times. For all infusions, vital signs must be 
monitored pre-infusion, every 15 minutes until the end of infusion, and thereafter, every 
30 minutes until the infusion line is removed (see Appendix 1, Appendix 2 and Appendix 3
for further details).
Study drug should be given as IV infusion over 2 hours for the first three doses and if 
well tolerated, the infusion time can be reduced to one hour in subsequent doses. Date, 
start and end time of infusions should be recorded on the eCRF. The study drug should 
be administered through a dedicated line with an inline filter. Intravenous infusion pumps 
should be used to control the infusion rate of study drug. Study drug should not be 
administered as an IV push or bolus. After the end of infusion, the IV line should remain 
in place for a minimum of 1 hour for all infusions. If no infusion-related symptoms occur 
within 1 hour post-infusion, the infusion line may be removed. 
If an IRR develops, the infusion should be temporarily interrupted. The participant should 
be monitored until complete resolution of the symptoms and treated as clinically 
indicated. Upon resolution of symptoms, the infusion may be resumed at 50% of the 
previous infusion rate. For the management of IRRs and hypersensitivity reactions, see 
Section 5.2.1 and Table 1.
In Part 3, if a patient had experienced an IRR at previous visit, the rate of infusion 
should be reduced at the subsequent visit and 2 hours duration of infusion should be 
considered. Rate of infusion may be increased again in case of ≤Grade 1 events in the 
previous cycle.

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To reduce the risk of IRRs, 2000 mg will be infused on Day 1 followed by an up-titration 
to the full dose of 4500 mg (65 kg body weight) / 3500 mg (65 kg body weight) on the 
second infusion (Day 28) during Part 1. Participants receiving placebo during Part 1 and 
randomized to the high dose at the start of Part 2 (extension) will receive 2000 mg IV on 
Week 56 followed by an up-titration to the full dose of 4500 mg (65 kg body weight) or 
3500 mg (65 kg body weight) on the second infusion (Week 60).
Guidelines for dosage modification and treatment interruption or discontinuation are 
provided in Section 5.2.1.
Cases of accidental overdose or medication error along with any associated AEs, should 
be reported as described in Section 5.3.5.11.
4.4.3
Investigational Medicinal Product Accountability
All IMPs (RO7046015) required for completion of this study will be provided by the 
Sponsor. The investigational site will acknowledge receipt of IMPs via IxRS, to confirm 
the shipment condition and content. Any damaged shipments will be replaced. 
Temperature excursion will be evaluated by the Sponsor/CRO. 
The Investigator is responsible for the control of drugs under investigation. Adequate 
records of the receipt (e.g., Drug Receipt Record) and disposition (e.g., Drug 
Inventory/Dispensing Log) of the study drug must be maintained. The Drug 
Inventory/Dispensing Log must be kept current and should contain the following 
information:

The identification of the patient to whom the study drug was dispensed (for example 
patient date of birth).

All records and drug supplies must be available for inspection by an unblinded 
Monitor [at every monitoring visit].
IMPs will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure or returned to the Sponsor with the appropriate 
documentation. The site's method of IMP destruction must be agreed upon by the 
Sponsor/CRO. Local or institutional regulations may require immediate destruction of 
used investigational medicinal product for safety reasons. In these cases, it may be 
acceptable for investigational study site staff to destroy dispensed investigational 
product before a monitoring inspection provided that source document verification is 
performed on the remaining inventory and reconciled against the documentation of 
quantity shipped, dispensed, returned, destroyed and provided that adequate storage 
and integrity of drug has been confirmed. 
The site must obtain written authorization from the Sponsor/CRO before any IMP is 
destroyed, and IMP destruction must be documented on the appropriate form.

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Written documentation of destruction must contain the following:

Identity [batch number] of investigational product[s] destroyed

Quantity of investigational product[s] destroyed

Date of destruction

Method of destruction

Name and signature of responsible person [or company] who destroyed 
investigational product[s].
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the Drug Inventory/Dispensing Log.
4.4.4
Post-trial Access to RO7046015
The Sponsor will offer continued access to study drug (RO7046015) free of charge to 
eligible patients in accordance with the Roche Global Policy on Continued Access to 
Investigational Medicinal Product, as outlined below.
A patient will be eligible to receive study drug (RO7046015) after completing the study 
if all of the following conditions are met:

The patient has a life-threatening or severe medical condition and requires 
continued Sponsor study drug treatment for his or her well-being

There are no appropriate alternative treatments available to the patient

The patient and his or her doctor comply with and satisfy any legal or regulatory 
requirements that apply to them
A patient will not be eligible to receive study drug (RO7046015) after completing the 
study if any of the following conditions are met:

The Sponsor study drug is commercially marketed in the patient's country and is 
reasonably accessible to the patient (e.g., is covered by the patient's insurance or 
wouldn't otherwise create a financial hardship for the patient)

The Sponsor has discontinued development of the drug or data suggest that the 
drug is not effective for PD

The Sponsor has reasonable safety concerns regarding the drug as treatment for PD

Provision of the drug is not permitted under the laws and regulations of the 
patient's country

Patient is eligible to enroll in an ongoing RO7046015 open-label study
4.5
CONCOMITANT THERAPY
Concomitant therapy includes any medication, e.g., prescription drugs, over-the-counter 
drugs, approved dietary and herbal supplements, nutritional supplements and any non-
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smoking cessation therapy, and rehabilitative therapy) used by a patient from at least 
90 days prior to screening until the follow-up visit. All concomitant medications should be 
reported to the Investigator and recorded on the Concomitant Medications electronic 
Case Report Form (eCRF).
All medication administered to manage adverse events should also be recorded on the 
Adverse Event eCRF.
4.5.1
Permitted Therapy 
4.5.1.1
For Participants on MAO-B Inhibitor Therapy
Participants who are currently under treatment for PD with a MAO-B inhibitor (rasagiline 
or selegiline), should be on a stable dose for at least 90 days prior to baseline and 
during the first year of the study (prior to extension). These patients will be treated with 
stable daily doses as recommended by the USPI or SmPC for rasagiline monotherapy 
and selegiline monotherapy and should not increase doses or switch between different 
MAO-B inhibitors during the study. Furthermore, if a participant is on a stable and well 
tolerated treatment regimen of a combination of a selective MAO-B inhibitor (rasagiline 
or selegiline) and an antidepressant for a period of at least 6 months prior to baseline, 
he/she may, at the discretion of the treating physician and in accordance with the local 
standard of care, continue on this therapy (without increasing the dosage) for the 
duration of their participation in the study. 
Participants that are untreated at baseline should not start MAO-B inhibitor treatment 
during the 52-week placebo controlled period (Part 1). If participants do start MAO-B 
inhibitor treatment at any time during the study, they will also complete the assessments 
described in the SoA under “prior to start of dopaminergic/symptomatic PD treatment”. 
Likewise, any changes of MAO-B inhibitor treatment and the reasons will be recorded.
4.5.1.2
Other Permitted Therapy
Participants who are currently being treated with antidepressants or anxiolytics should 
remain on a stable dose for at least 90 days prior to baseline and, barring any 
unforeseen circumstances, remain on that dose for the duration of the study.
Participants who are receiving anti-epileptic medication for non-seizure related treatment 
should remain on a stable dose for at least 60 days prior to baseline.
Participants who use oral contraceptives, hormone-replacement therapy, or other 
maintenance therapy should continue their use.
All preventive/routine immunizations (e.g., tetanus/diphtheria booster, herpes zoster, 
pneumococcal pneumonia, influenza) should be administered at least 30 days prior to 
baseline. In the event that an immunization is needed during the study, it should be 
administered between the third and 12th infusion in Part 1 or Part 2. The timing of the 
vaccination should be around mid-cycle (between 2 infusions).  

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Use of anti-platelet medications such as low dose ASA, clopidogrel, prasugrel, or 
ticagrelor prescribed for the prevention of cardiovascular events are permitted.
4.5.2
Prohibited Therapy 
4.5.2.1
MAO-B Inhibitor Therapy
Participants on MAO-B inhibitor therapy for PD must not receive fluoxetine, fluvoxamine, 
meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including 
other selective MAO-B inhibitors, because of the risk of serotonin syndrome. At least 14 
days should elapse between discontinuation of the selective MAO-B inhibitor and 
initiation of treatment with these medications. Concomitant use of St. John’s wort, 
cyclobenzaprine and dextromethorphan is also prohibited (see MAO-B inhibitor 
prescribing information). 
Due to the potential risk of serotonin syndrome, starting a new treatment with any 
antidepressant in a participant already on a stable course of MAO-B inhibitor treatment 
will be decided on a case-by-case basis after a discussion between the Investigator and 
the Sponsor. 
Participants that are untreated at baseline should not start MAO-B inhibitor treatment 
during the 52-week placebo-controlled period (Part 1). If participants do start MAO-B 
inhibitor treatment at any time during the study, they will also complete the assessments 
described in the SoA under “prior to start of dopaminergic/symptomatic PD treatment”. 
Likewise, any changes of MAO-B inhibitor treatment and the reasons will be recorded.
4.5.2.2
Other Prohibited Therapy
Other prohibited therapy includes: 

Antipsychotics (including clozapine and olanzapine), metoclopramide, alpha 
methyldopa, flunarizine, amoxapine, amphetamine derivatives, reserpine, bupropion, 
buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, 
phentermine, phenylpropanolamine and modafinil within 90 days prior to baseline 
and over the study period. 

Immunomodulating drugs within 30 days prior to baseline and over the study period.

For participants undergoing Lumbar Puncture, oral anticoagulants (Direct Factor Xa 
Inhibitors and Direct Thrombin Inhibitors), low-molecular-weight heparin (LMWH), 
warfarin (Coumadin) acenocoumarol and phenprocoumon are prohibited.

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4.5.3
Other Symptomatic PD Therapy
During Part 1 (52-week double blind placebo-controlled period), participants should not 
start symptomatic treatment for PD, including COMT inhibitors (entacapone, tolcapone), 
amantadine or anticholinergics, dopaminergic medication (levodopa), both ergot and 
non-ergot (pramipexole, ropinirole, rotigotine) dopamine agonists, and MAO-B inhibitors 
(see Section 4.5.2.1). Some participants may experience worsening of their PD 
symptoms to an extent that they cannot tolerate in their personal or professional life. 
These patients may start symptomatic treatment according to local guidelines during a 
regular study visit after completing the assessments described in the SoA under visit 
“prior to start of dopaminergic/symptomatic PD treatment”. Investigators will record the 
reasons and the type and dose of symptomatic treatment started. These participants will 
continue in the study as per their regular scheduled study visits.
During the extensions (Part 2 and Part 3), symptomatic treatment for PD including but 
not limited to COMT inhibitors (entacapone, tolcapone), amantadine or anticholinergics, 
dopaminergic medication (levodopa), both ergot and non-ergot (pramipexole, ropinirole, 
rotigotine) dopamine agonists may be prescribed.
4.5.4
Dietary Restrictions
Foods with a high tyramine content should be avoided by participants on selegiline or 
rasagiline due to the potential for a hypertensive reaction (see local label).
4.6
STUDY ASSESSMENTS 
4.6.1
Description of Study Assessments
All examinations listed below will be performed according to the Schedule of 
Assessments (SoA) outlined in Appendix 1, Appendix 2 and Appendix 3. A 
recommended sequence of assessments to be carried out at each visit is outlined in 
Appendix 4.
Note that in those patients that start dopaminergic treatment during the course of the 
study, the majority of functional assessments (including MDS-UPDRS Part I II III) are 
to be performed prior to administration of dopaminergic treatment on that day. Only 
selected functional assessments such as MDS-UPDRS Parts III IV will be performed at 
least 1 hour after dopaminergic treatment.
4.6.1.1
Medical History and Demographic Data
Medical history includes clinically significant diseases, surgeries, reproductive status, 
smoking history, use of alcohol and drugs of abuse and all medications 
(e.g., prescription drugs, over-the-counter drugs, herbal or homeopathic remedies, 
nutritional supplements) used by the patient within 90 days prior to the screening visit.
Demographic data will include age, sex, and self‑reported race/ethnicity, where 
applicable. The patient’s number of years of education will also be recorded.

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4.6.1.2
Physical and Neurological Examinations
A complete physical examination will be performed at the time-points specified in the 
SoA (see Appendix 1, Appendix 2 and Appendix 3). The examination should include an 
evaluation of the head, eyes, ears, nose and throat (HEENT), neck and lymph nodes, 
and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, 
genitourinary, and neurological systems.
The physical exam will NOT include pelvic, rectal or breast exams.
An abbreviated physical examination will be performed at all other study visits in Part 1 
and 2. It will include HEENT, heart & lung exams and any assessment based on the 
complaints expressed by the patient at visit. In Part 3, abbreviated physical examination 
will be performed as indicated in the SoA (see Appendix 3) and may be performed
outside of SoA at any visit if deemed necessary by the investigator or if the patient 
expresses any complaints / presents any symptoms at an in-clinic visit.
Any abnormality identified at baseline should be recorded on the General Medical 
History and Baseline Conditions eCRF.
Changes from baseline abnormalities should be recorded in participant’s notes. New or 
worsened clinically significant abnormalities should be recorded as adverse events on 
the Adverse Event eCRF.
Height will only be recorded at screening. Weight will be recorded at time-points for 
complete Physical Examination as specified in the SoA (Appendix 1, Appendix 2 and 
Appendix 3).
A neurological exam will also be conducted at screening, baseline and every six months, 
and at the last completed visit. A neurological exam may be performed at any visit if 
deemed necessary by the investigator (e.g., in case of an adverse event).
4.6.1.3
Vital Signs
Vital signs will include measurements of temperature, respiratory rate, pulse rate, and 
systolic and diastolic blood pressure while the patient is in a semi-supine position (upper 
body is not completely horizontal but rather tilted at an angle of about 45°) after the 
patient has been resting for approximately 5 minutes at each visit. Additionally, a single 
BP and pulse will be obtained after 2 minutes of standing for orthostatic vital signs at the 
time-points specified in the SoA (Appendix 1, Appendix 2 and Appendix 3). When 
possible, the same arm should be used for all blood pressure measurements.
In Part 1 and 2, blood pressure (BP), pulse rate, respiratory rate and body temperature 
will be recorded at the time-points specified in the SoA (Appendix 1 and Appendix 2). In 
Part 3, blood pressure (BP), pulse rate and respiratory rate will be recorded at the 
time-points specified in the SoA; body temperature may be taken at any visit if deemed 
necessary by the Investigator but is no longer mandatory at each visit (Appendix 3). 

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Any clinically significant abnormal vital sign value should be repeated to ensure 
accuracy. If the abnormality persists upon repeat measurement, the patient should be 
assessed by the Investigator.
Blood pressure, pulse rate and respiratory rate should be obtained in a quiet room at a 
comfortable temperature, with the participant’s arm unconstrained by clothing or other 
material. All measurements will be obtained from the same arm and, with the same cuff 
size, using a well-calibrated automatic instrument with a digital readout, throughout the 
study (the “ideal” cuff should have a bladder length that is 80% and a width that is at 
least 40% of arm circumference [a length-to-width ratio of 2:1]). The automatic cuff 
should be placed on the designated arm prior to dosing. The participant should be asked 
to remove all clothing that covers the location of cuff placement. The individual should be 
comfortably seated, with the legs uncrossed, and the back and arm supported, such that 
the middle of the cuff on the upper arm is at the level of the right atrium (the mid-point of 
the sternum). After the patient has been resting in a semi-supine position for at least 
5 minutes, blood pressure, pulse rate and respiratory rate will be obtained. 
4.6.1.4
Electrocardiograms
Triplicate ECG recordings (i.e., three useful ECGs without artifacts) will be obtained 
within approximately 2-5 minutes at each specified time-point. The average of the three 
readings will be used to determine ECG intervals (e.g., PR, QRS, QT). In Part 3, 
triplicate ECG recordings or single ECG recordings will be obtained as detailed in the 
SoA (Appendix 3). Whenever possible, the same brand/model of a standard high-quality, 
high-fidelity electrocardiograph machine equipped with computer-based interval 
measurements should be used for each participant. The conditions should be as close 
as possible to pre-dose time-points; this includes but is not limited to food intake, activity 
level, stressors and room temperature.
To minimize variability, it is important that participants be in a resting position 
for10 minutes prior to each ECG evaluation. Body position should be consistently 
maintained for each ECG evaluation to prevent changes in heart rate. Environmental 
distractions (e.g., television, radio, conversation) should be avoided during the pre-ECG 
resting period and during ECG recording. ECGs should be performed prior to any 
scheduled vital sign measurements, blood draws and study drug infusion. In some cases, 
it may be appropriate to repeat abnormal ECGs to rule out improper lead placement as 
contributing to the ECG abnormality.
For safety monitoring purposes, the Investigator or designee must review, sign, and date 
all ECG tracings. Paper copies will be kept as part of the participant’s permanent study 
file at the site. ECGs will be analyzed at a central laboratory.
Digital ECG recordings will be analyzed and read by a central reader and available on 
the vendor’s ECG portal. The ECG data from the central reader will include heart rate, 
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U-wave morphology and overall ECG interpretation. T-wave information will be captured 
as normal or abnormal, U-wave information will be captured in two categories: 
absent/normal or abnormal.
4.6.1.5
Laboratory Assessments
Normal ranges for the study laboratory parameters must be supplied to the Sponsor 
before the study starts. Laboratory safety tests shall be collected at time-points specified 
in the SoA (Appendix 1, Appendix 2 and Appendix 3).
Additional blood or urine samples may be taken at the discretion of the Investigator if the 
results of any test fall outside the reference ranges, or clinical symptoms necessitate 
additional testing to monitor participant safety. Where the clinical significance of 
abnormal lab results is considered uncertain, screening lab tests may be repeated once 
per discretion of the Investigator before randomization to confirm eligibility. If there is an
alternative explanation for a positive urine or blood test for drugs of abuse, e.g., previous 
occasional intake of a medication or food containing for example codeine, 
benzodiazepines or opiates, the test could be repeated to confirm washout.
After randomization, in the event of unexplained abnormal clinically significant laboratory 
test values, the tests should be repeated immediately and followed up until they have 
returned to the normal range and/or an adequate explanation of the abnormality is found. 
Results from local or central clinical laboratory testing will be either recorded on the 
eCRF or be received as electronically produced laboratory reports submitted directly 
from the central laboratory and loaded on the eCRF.
Blood and urine samples will be collected for the following clinical laboratory tests at the 
time-points indicated in the SoAs (Appendix 1, Appendix 2 and Appendix 3).

Hematology (leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, differential 
count [neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells]).

Serum chemistry (sodium, potassium, chloride, bicarbonate, glucose (fasting for 
screening visit), urea, creatinine, protein, albumin, phosphate, calcium, total and 
direct bilirubin, alkaline phosphatase, ALT, AST, urate, LDH).

Coagulation (INR, aPTT, PT)

Viral serology:
–
HIV (specific tests HIV-1 antibody, HIV-1/2 antibody, HIV-2 antibody)
–
Hepatitis B surface antigen (HBsAg)
–
Total hepatitis B core antibody (HBcAb)
–
Hepatitis C virus (HCV) antibody
–
HCV RNA test for successfully treated HCV patients

Urinalysis: A midstream, clean-catch urine specimen will be collected for dipstick 
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significant positive result (i.e., confirmed by a positive repeated dipstick sample), 
urine will be sent to the local laboratory for microscopy and/or culture. If there is an 
explanation for the positive dipstick result, e.g., menses, it should be recorded, and 
there is no need to send for additional testing.

Urine drug screen: This should at a minimum include: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids, and benzodiazepines (for further details regarding 
the type of urine drug screen and the handling of a positive urine drug screen for 
benzodiazepines, see Section 4.2.3, exclusion criterion 10 e). 

Lipids (cholesterol, LDL cholesterol, HDL cholesterol, triglycerides)

Thyroid hormones (free T4 and TSH)

Other hormones (estradiol, follicle stimulating hormone [FSH], luteinizing hormone 
[LH] in females).

All women who are not post-menopausal or surgically sterile will have a serum 
pregnancy test at screening. Urine pregnancy tests will be performed prior to dosing 
and all DaT-SPECT scans based on patient age/menopausal status. If a urine 
pregnancy test is positive, it must be confirmed by a blood pregnancy test. 

CSF: erythrocyte and leukocyte cell counts, protein and glucose.
4.6.1.6
Pharmacokinetic Assessments
Serum samples for population PK analysis will be collected in all randomized 
participants in this study. These samples will be collected at the time-points specified in 
the SoA (Appendix 1, Appendix 2 and Appendix 3). On each of the specified visits in 
Parts 1 and 2, and in the first year of Part 3, one sample pre-dose and one sample 
post-dose at the end of the infusion will be collected. In Years 2 to 5 of Part 3, one 
sample predose will be collected at the specified visits in the SoA. In addition, a sample 
will be collected at any time on Days 7 and 14 (of Part 1) for the first 90 participants 
enrolled in the US. The date and time of each sample will be recorded in the eCRF.
RO7046015 levels will be analyzed by using validated assays. Samples from 
participants randomized to placebo will not be analyzed in the first instance, but will be 
retained for subsequent analysis if appropriate.
Remaining PK volume may also be used for additional validation experiments after the 
mentioned intended uses.
Details on sampling procedures, sample storage and shipment are given in the 
laboratory manual.
4.6.1.7
Immunogenicity Assessments
Although RO7046015 is a humanized antibody, there is a risk that ADA against 
RO7046015 could develop, potentially reducing its efficacy and/or potentially resulting in 
symptomatic hypersensitivity reaction, in particular immune-complex reactions.

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Blood samples for anti-drug antibodies (ADA) will be taken as described in the SoA 
(Appendix 1, Appendix 2 and Appendix 3). Additional ADA samples will be drawn at the 
time of treatment discontinuation or at the safety follow-up visit and in participants who 
experience a Grade 2 IRR and in participants with clinical signs of hypersensitivity 
reaction, in particular immune-complex reaction. In any case, for each collected ADA 
sample, a corresponding PK sample will be collected at the same time-point for the 
determination of the RO7046015 concentration. The date and time of each sample will 
be recorded in the eCRF.
Validated screening, confirmatory, and titer assays will be employed to detect ADAs 
against RO7046015. 
Samples from participants randomized to placebo will not be analyzed in the first 
instance, but will be retained for subsequent analysis if appropriate.
If required, remaining ADA samples may also be used for additional assay 
development/validation experiments. 
Details on sampling procedures, sample storage and shipment are given in the 
laboratory manual.
4.6.1.8
Biomarker Samples
The following samples will be collected to analyze biomarkers associated with PD:

Serum and plasma biomarker sample

Whole blood for clinical genotyping

Lumbar puncture for CSF (optional)
Lumbar puncture will be performed on consenting participants only. Note: baseline 
LP should be performed during the screening period prior to Day -4 to allow 
recovery before dosing. The LP should be performed in the morning (between 08:00
and 12:00 hours) to minimize potential diurnal variation of CSF parameters. Any 
participants with a headache due to the LP should not be dosed until it has resolved. 
Participants taking low-dose aspirin (ASA) may be at a higher risk of LP 
complications. At the discretion of the Investigator, if not contraindicated, low dose 
ASA may be discontinued for a period of time prior to performing the LP; stop and 
start dates must be documented on the appropriate Concomitant Medication eCRF. 
An aliquot of the CSF samples will be used for local laboratory analysis (erythrocyte 
and leukocyte cell counts, protein, and glucose) to test for signs of infection or 
inflammation while the remainder of the sample will be sent for central biomarker 
assessment.   

Punch biopsies to collect skin tissue from the cervical paravertebral region will be 
performed under local anesthesia (lidocaine). If skin biopsies are collected at visits 
with study drug administration, they should be collected pre-dose.

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
All biomarker samples, including samples from screen failures, will be destroyed 
within 5 years after the date of final clinical study report. Other residual material 
(may include blood, serum specimens, extracts, tissue, on-study blocks, slides, etc.) 
will be destroyed within 5 years after the final clinical study report unless the patient 
gives specific consent for the remainder of the sample(s) to be used for optional 
exploratory research within the Research Biosample Repository (RBR). If the patient 
provides consent for optional exploratory research, the samples will be stored until 
no longer needed or used up.
For sampling procedures, storage conditions, and shipment instructions, see the 
separate laboratory manual.
Based on continuous analysis of the data in this study and other studies, any sample 
type not considered to be critical for safety may be stopped at any time if the data from 
the samples collected does not produce useful information.
Data arising from all biosamples including samples for analyses of inherited DNA will be 
subject to the confidentiality standards described in Section 8.4.
The sample collected for DNA extraction may be used for whole genome sequencing 
(WGS) and other genetic analysis and may be sent to one or more laboratories for 
analysis.
Genomics is increasingly informing researcher's understanding of disease pathobiology. 
WGS provides a comprehensive characterization of the genome and, along with clinical 
data collected in this study, may increase the opportunity for developing new therapeutic 
approaches. Data will be analyzed in the context of this study but will also be explored in 
aggregate with data from other studies. The availability of a larger dataset will assist in 
identification of important pathways, guiding the development of new targeted agents.
4.6.1.9
Disease-Specific Assessments
Movement Disorder Society-Unified Parkinson's Disease Rating Scale
(In-clinic)
The MDS-UPDRS is a multimodal scale assessing both impairment and disability and is 
separated into four subscales (Parts I-IV). The MDS-UPDRS includes components 
assessed by the rater as well as sections completed by the participant. The 
MDS-UPDRS rater will be a trained, experienced movement disorder specialist who 
should not be involved in the clinical assessments at dosing days as described in 
Appendix 4 (specifically AE reporting, concomitant medication, physical or neurological 
exams). To reduce variability, every effort should be made to have the same rater 
perform the ratings for an individual participant throughout the course of the study. The 
MDS-UPDRS rater should also rate the Modified Hoehn and Yahr Stage and the CGI-I.

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
Part I assesses non-motor experiences of daily living and is comprised of two 
components:
–
Part IA contains 6 questions that are assessed by the rater.
–
Part IB contains 7 questions that are part of the Patient Questionnaire 
completed by the participant.

Part II assesses motor experiences of daily living. There are an additional 
13 questions that are also part of the Patient Questionnaire completed by the 
participant.

Part III assesses the motor signs of PD and is administered by the rater. Part III 
contains 33 scores based on 18 items, several with right, left or other body 
distribution scores.

Part IV assesses motor complications, dyskinesias and motor fluctuations using 
historical and objective information. The Investigator will complete this assessment 
once a participant has started dopaminergic treatment.
For each question a numeric score is assigned between 0-4, where 0Normal, 
1Slight, 2Mild, 3Moderate, 4Severe. Composite scores (for each Part and total) 
are determined by summing the numeric values of each question.  
In participants that do not receive any dopaminergic (levodopa or dopamine agonist) 
PD treatment, only MDS-UPDRS Parts I, II and III will be assessed and total MDS-
UPDRS score in this population is the sum of Parts I, II and III (primary outcome 
measure).
Participants who have started dopaminergic treatment (levodopa or dopamine agonist) 
during the course of the study will continue in the study, as per their regular scheduled 
study visits. For these participants, the MDS-UPDRS (Parts I, II, III and IV) and Digital 
Biomarker in-clinic assessments (Section 4.6.1.9) will be performed in a practically 
defined “Off” state – no levodopa or dopamine agonist medication since the prior 
evening, and Part III (motor assessment) will be repeated at least one hour after 
receiving medication in clinic (“On” state). These participants will need to be reminded 
not to take dopaminergic treatment prior to their study visit in which MDS-UPDRS is 
administered, but to bring their dopaminergic medication to the study visit, to take their 
regular dopaminergic treatment dose at least one hour prior to the “On” state 
assessments. 
In Part 1 and Part 2, MDS-UPDRS Part III administration to participants is videotaped at 
each administration of MDS-UPDRS scale, and videotapes are transferred to a central 
vendor. In parallel to the MDS-UPDRS ratings from trained site raters, central vendor will 
centrally score MDS-UPDRS Part III from videotapes to address consistency and 
accuracy.

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Hoehn and Yahr Stages (In-clinic)
The H&Y provides a global assessment of the severity of Parkinson’s disease based on 
clinical findings and functional disability. The scale allocates stages from 0 to 5 to 
indicate the relative level of motor disability and is a commonly used system for 
describing how the symptoms of PD progress. This scale is included within the 
MDS-UPDRS and will be completed for all participants.

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.

Stage 4: Severe disability, but still able to walk or stand unassisted.

Stage 5: Wheelchair-bound or bedridden unless assisted.
Modified Hoehn and Yahr Stages (In-clinic)
The mH&Y staging is an adaptation of the H&Y (see above) which includes two 
additional stages (1.5 and 2.5) to account for the intermediate course of Parkinson 
disease, mH&Y will be measured across this study as an exploratory endpoint to better 
understand changes in motor symptoms across the study. The mH&Y stage should be 
assessed by the same rater as the MDS-UPDRS.

Stage 0: No symptoms.

Stage 1: Symptoms on one side of the body only.

Stage 1.5: Symptoms on one side of the body and axial involvement

Stage 2: Symptoms on both sides of the body. No impairment of balance.

Stage 2.5: Mild symptoms on both sides of the body with recovery on pull test.

Stage 3: Balance impairment. Mild to moderate disease. Physically independent.

Stage 4: Severe disability, but still able to walk or stand unassisted.

Stage 5: Wheelchair-bound or bedridden unless assisted.
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) (In-clinic)
The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) is a 10-item self-
rated questionnaire to assess sleep-wake disturbances. Patients with clinical 
characterizations of sleep behavior disorder may represent early manifestations of 
progressive neurodegenerative disorders, including Parkinson’s disease, thus making 
this an important tool for early diagnosis and stratification in longitudinal prospective
studies.
DaT-SPECT
DaT-SPECT (DaT (123I-FP-CIT) SPECT) assessments will be performed at Screening as 
part of the eligibility criteria and for consideration as a baseline scan for statistical 

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analyses. Further DaT-SPECT scans will be acquired after 52 weeks, 104 weeks, Part 3 
Week 104 and Part 3 Week 208 or upon early termination. The technical details and 
communication lines will be outlined in a separate DaT-SPECT technical operations 
manual. Scans will be reviewed and managed by a central reader DaT-SPECT Core Lab 
and it will be the assessment of this central reader that will be used for eligibility decision 
and for efficacy analyses.
Imaging Procedure: Women of childbearing potential must have a confirmed negative 
urine pregnancy test just prior to injection of DaTSCAN™. Before the DaTSCAN™ 
injection, participants will be pre-treated with stable iodine (e.g., 10 drops of a saturated 
solution of potassium iodide or other liquid formulation or tablets, as per local standard 
practice) to reduce the uptake of DaTSCAN™ by the thyroid. Patients with a 
hypersensitivity to iodine may receive an alternative thyroid blocking agent (e.g., 
potassium perchlorate or sodium perchlorate). Participants will then be injected with 3-5 
mCi of tracer. About 4 hours (30 minutes) following the injection, participants will 
undergo SPECT imaging on the camera. The data and quality assurance procedures to 
be employed in this study, as well as technical details on DaT-SPECT acquisition will be 
provided in a separate DaT-SPECT technical operations manual.
Magnetic Resonance Imaging (MRI)
The MRI should be performed using a 3-Tesla (3T) magnet. If a 3T magnet is not 
available in reasonable proximity to the study center, a 1.5T magnet may be used. All 
technical details and communication lines will be outlined in a separate MRI manual. 
Qualifying MRI scans will be performed on healthy volunteers having provided informed 
consent at each MRI center as part of the certification process with the MRI service 
provider. All MRI scans will be managed by a central MRI Core Lab monitoring and 
ensuring the integrity and quality of the acquired data.
Eligibility and safety MRI assessments (fluid-attenuated inversion recovery [FLAIR], 
diffusion-weighted imaging [DWI], gradiant echo [GRE], structural MRI [sMRI]) will be 
performed at screening as part of the eligibility criteria. Further safety MRI scans will be 
acquired at the time-points specified in the SoA (Appendix 1, Appendix 2 and 
Appendix 3), upon early termination and prior to start of DT. For assessing MRI-related 
study eligibility criteria at screening and for safety monitoring, the assessment by the 
local neuroradiologists will be used.
Exploratory efficacy MRI assessments (including DTI, ASL, rs-fMRI, NM-MRI, iron 
imaging) as described in Section 3.2.7.2 will be performed at Screening for 
consideration as a baseline scan, after 52 and 104 weeks of treatment, at Part 3 Week 1, 
after Part 3 Week 104 and Part 3 Week 208, and upon early termination/withdrawal from 
the study. 
Participants who have started dopaminergic treatment (levodopa or dopamine agonist) 
will have the MRI assessment in a practically defined ‘Off’ state. These participants will 

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need to be reminded not to take dopaminergic treatment on the day of each study visit 
in which MRI is acquired. 
MRIs should not be performed unless at least 3 to 4 hours have passed since a lumbar 
puncture.
Clinical Global Impression of Severity and Improvement (CGI-S and CGI-I) 
(In-clinic)
The generic Global Impression is a measure commonly used in PD clinical trials to 
provide concise information on overall health state (Guy 1976). The CGI-I should be 
assessed by the same rater as the MDS-UPDRS.
The severity component (CGIS) is intended as a measure of disease severity.
1Normal, not at all ill; 2Borderline ill; 3Mildly ill; 4Moderately ill; 5Markedly ill; 
6Severely ill; 7Among the most extremely ill patients.
The improvement component (CGI-I) is intended as a measure of change in health state. 
A 7-point clinician-based (CGI-I) global impression of improvement will be employed:
1Very much improved; 2Much improved; 3Minimally improved; 4No change; 
5Minimally worse; 6Much worse; 7Very much worse
Mini Mental State Examination (MMSE) (In-clinic)
The Mini Mental State Examination (MMSE) consists of a set of standardized questions 
to assess a participant’s mental status and identify the individual’s general level of 
impairment. The questions target five areas; orientation, short term memory retention, 
attention, short term recall and language. This will be used as an inclusion criterion, to 
ensure that the patient is not cognitively impaired.
The Montreal Cognitive Assessment (MoCA) (In-clinic)
In early Parkinson’s disease, patients usually perform in the normal range on the widely 
used MMSE. The Montreal Cognitive Assessment (MoCA) is a rapid screening 
instrument like the MMSE but was developed to be more sensitive to patients presenting 
with mild cognitive complaints. It briefly assesses short term and working memory, 
visuospatial abilities, executive function, attention, concentration, language and 
orientation (Nasreddine et al 2005).
Schwab and England Activities of Daily Living (SE-ADL) (In-clinic)
The SE-ADL is a single item scale assessing Activities of Daily Living on a scale ranging 
from 0% (bedridden) to 100% (completely independent), using 10% intervals (Schwab & 
England 1969).

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Digital Biomarker Assessments (Smartphone & Wrist-Worn Wearable)
Each participant will receive a preconfigured smartphone and wrist-worn wearable with 
installed software for the digital biomarker assessments. They will use the devices and 
software to assess motor and non-motor symptoms, as well as activities associated with 
routine daily living. The smartphone will also be used to complete selected PROs (see 
Section 4.6.1.10). 
Digital Biomarker Remote Monitoring
Participants will be provided and trained on the devices during screening. During the 
study, participants will be instructed to conduct an “Active Test” every day in Part 1 and 
Part 2, and as per SoA in Part 3, at approximately the same time (ideally in the morning, 
after breakfast). The “Active Test” consists of a short, preconfigured sequence of tasks 
that assess motor symptoms (upper and lower body movements, upper limb dexterity, 
voice/speech) and non-motor symptoms (including an eSDMT for cognition). For 
“Passive Monitoring”, participants will be instructed to carry the smartphone and wear 
the wrist-worn wearable throughout the day as they go about their daily routine. Selected 
PROs will be administered on the smartphone to reduce the site visit burden.
Device sensor data will be recorded continuously, throughout the “Active Tests” and 
“Passive Monitoring”. Sound will only be recorded during selected “Active Test” tasks. 
Data are encrypted and uploaded to secure servers whenever the phone is connected to 
WIFI.
Participants are asked to charge the devices overnight. If participants have a WIFI 
network at home, they are encouraged to connect their smartphone to enable data 
transfer. If no WIFI network is available, the sensor data will be transferred during site 
visits or after the devices have been returned.
Digital Biomarker In-Clinic Assessments
In Part 1 and Part 2, participants are instructed to bring the smartphone and wearable 
to every clinic visit to check adherence and technical status of the devices. In Part 1 and 
Part 2, participants will receive replacement device sets if they are defective. In Part 3, 
device sets may not be replaced if they are defective. In Part 3, participants are 
instructed to bring the sets to the visits with in-clinic digital biomarker assessments 
once a quarter. 
In Part 1 and Part 2, at selected clinic visits, participants will be asked to conduct the 
“Active Test” tasks and two additional in-clinic only assessments (selected items from 
the Berg Balance Scale and the Timed-Up and Go Test) under the supervision of a 
person trained on the digital biomarker approach. In Part 3 participants will only 
perform the “Active Tests” at the specified in-clinic site visits.
For participants who have started dopaminergic treatment (levodopa or dopamine 
agonist), the in-clinic assessments will be performed in a practically defined “Off” state 

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(i.e., no levodopa or dopamine agonist medication since the evening before). The in-
clinic assessments will be repeated not earlier than one hour after receiving medication 
in clinic (“On” state).
The smartphone and wearable must be returned to the clinic in cases where the subject 
does not meet eligibility criteria, at the end of the study and upon early termination.
At the end of the study or at the time when the subject has completed the study, 
participants will be asked to complete a pen & paper satisfaction survey on how they 
experienced using the smartphone and wrist-based wearable during the study.
The full detailed digital biomarker is described in the ‘PD Digital Biomarker (Smartphone) 
Manual’. 
Columbia−Suicide Severity Rating Scale (C-SSRS) (In-clinic)
The C-SSRS (Posner et al 2011) is an assessment tool used to assess the lifetime 
suicidality of a patient (C-SSRS at baseline) as well as any new instances of suicidality 
(C-SSRS since last visit). The structured interview prompts recollection of suicidal 
ideation, including the intensity of the ideation, behavior, and attempts with 
actual/potential lethality. The “C-SSRS at Baseline” will be collected at baseline and the 
“C-SSRS since Last Visit” will be collected at subsequent visits.
The C-SSRS will be conducted at the time-points indicated in the SoA. The assessment 
will be completed by a certified C-SSRS rater after interviewing the participant at the visit.
4.6.1.10
Participant-Reported Outcomes
For a recommended order of assessments to be performed at each visit see Appendix 4.
PRO data will be elicited from the participant in this study to more fully characterize the 
clinical profile of the study drug. The PRO instruments, translated as required in the local 
language, will either be distributed by the Investigator staff and completed in their 
entirety by the participant at specified time‑points during the study (“In-clinic”), or 
participants will use an electronic device (“Smartphone”) to capture PRO questionnaire 
data.
To ensure instrument validity and that data standards meet Health Authority 
requirements, PRO questionnaires administered at the investigational site, should be 
self-administered prior to the administration of study treatment. 
Entries should be reviewed for completeness by the site staff during the visit and the 
participant should be requested to complete any blank items. Changes to the form 
should not be made once the participant has left the site for that visit.
39-item Parkinson’s Disease Questionnaire (PDQ-39) (In-clinic)
The PDQ-39 is a 39-item, self-administered questionnaire with eight domains of: Mobility 
(10 items); Activities of daily living (ADL, 6 items); Emotional well-being (6 items); Stigma 

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(4 items); Social support (3 items); Cognitions (4 items); Communication (3 items); and 
Bodily discomfort (3 items) (Peto et al 1995). Questions ask about the frequency with 
which participants have experienced difficulties due to having PD “during the last month”. 
All items are scored from 0 (never) to 4 (always). Summary indices can be calculated for 
both the total scale and the subscales: the lower the index, the better the Health-Related 
Quality of Life. Each scale is transformed to have a range from 0 (best, i.e., no problem 
at all) through to 100 (worst, i.e., maximum level of problem) with each scale being 
calculated as follows: scale scorethe total of the raw scores of each item in the scale 
divided by the maximum possible raw score of all the items in the scale multiplied by 100.
Patient Global Impression of Change (PGIC) (In-clinic)
The generic Global Impression is a measure commonly used in PD clinical trials to 
provide concise information on overall health state (Guy 1976). The change component 
is intended as a measure of change in health state and can be adapted for participant 
self-assessment (PGIC). A 7-point participant-based (PGIC) global impression of change 
will be employed.
PGIC: 1 = Very much improved; 2 = Much improved; 3 = Somewhat improved; 4 = No 
change; 5 = Somewhat worse; 6 = Much worse; 7 = Very much worse
Parkinson’s Disease Sleep Scale Revised Version (PDSS-2) (In-clinic)
The PDSS-2 is a 15-item, self-reported scale that asks about the frequency of various 
sleep and nocturnal disturbances, using a five-point response scale ranging from zero 
(never) to four (very frequent), with a total score ranging from zero (no disturbance) to 60 
(maximum nocturnal disturbance) (Trenkwalder et al 2011). The scale can be divided 
into three different domains that reflect the complexity of sleep problems in PD: 
1) nocturnal motor symptoms such as akinesia, early morning dystonia, tremor during 
waking period at night, periodic limb movements (PLM), restless behavior or immobility, 
and motor symptoms probably due to REM sleep behavior disorder (RBD); 
2) PD-specific nocturnal symptoms like hallucinations, confusion states, pain, muscle 
cramps, difficulties in breathing with snoring, and immobility; and 3) sleep-specific 
disturbances like insomnia, sleep maintenance, unrestored sleep in the morning, getting 
up at night to pass urine, and the overall subjective quality of sleep.
Scales for Outcomes in Parkinson’s Disease Assessment of Autonomic 
Dysfunction (SCOPA-AUT) (In-clinic)
The Scales for Outcomes in Parkinson’s disease assessment of autonomic dysfunction 
(SCOPA-AUT) is a 25-item self-administered test developed to evaluate autonomic 
symptoms, such as gastrointestinal and urinary problems, in patients with PD (Visser et 
al 2004). Region scores of: gastrointestinal (seven items); urinary (six items); 
cardiovascular (three items); thermoregulatory (four items); pupillomotor (one item); and 
sexual (two items for men and two for women) problems can also be derived. Higher 
scores reflect worse autonomic functioning.

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Hospital Anxiety and Depression Scale (HADS) (Smartphone)
The HADS is a 14-item self-rated scale yielding sub-scores for depression (7 items) and 
anxiety (7 items) (Snaith and Zigmond 2000).
Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire
(Smartphone)
The PAC-SYM is a 12-item self-report questionnaire subdivided in three symptom 
subscales (i.e., abdominal, stool, and rectal) (Frank et al 1999). The questionnaire asks 
about severity of symptoms in the past two weeks, using a five-point response scale 
from absent (0) to severe (4).
EuroQol EQ-5D-5L Questionnaire (Smartphone)
The EQ-5D-5L Questionnaire is a generic, preference-based health utility measure with 
questions about mobility, self‑care, usual activities, pain/discomfort, and 
anxiety/depression that are used to build a composite of the participant’s health status. 
The EQ‑5D-5L Questionnaire will be utilized in this study for economic modelling.
Diary Questions (Smartphone)
A series of novel diary questions assessing aspects of insomnia, REM sleep behavior 
disorder, daytime somnolence, bowel movements, autonomic system functioning 
(i.e., swallowing, overproduction of saliva, urine retention, perspiration and sensitivity to 
heat). Patient Global Impression of Severity will also be assessed via the Smartphone.
Once available, participants will also be asked about reasons for not performing the 
active tests.
4.6.1.11
Patient Engagement Application
The Smartphone Patient Engagement Application is an optional service that participants 
can opt-in to use to remind them of activities/tasks relevant to study compliance, 
e.g., attend study visits. The application also provides supportive guides to help 
participants to be aware of visit procedures, study information and instructions. 
Additional details are found in Appendix 5.
This application will no longer be used in Part 3.

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4.6.1.12
Samples for Research Biosample Repository
Overview of the Research Biosample Repository
The Roche Research Biosample Repository (RBR) is a centrally administered group of 
facilities for the long-term storage of human biologic specimens, including body fluids, 
solid tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides). The collection, 
storage and analysis of these specimens will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for participants in the future.
Specimens will be collected from participants who give specific consent to participate in 
this optional Research Biosample Repository. Collected specimens will be used to 
achieve the following objectives:

To study the association of biomarkers with efficacy, adverse events, or disease 
progression

To increase knowledge and understanding of disease biology

To study drug response, including drug effects and the processes of drug absorption 
and disposition

To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays
Approval by the Institutional Review Board or Ethics Committee
Sampling for the RBR is contingent upon the review and approval of the exploratory 
research and the RBR portion of the Informed Consent Form by each site's Institutional 
Review Board or Ethics Committee (IRB/EC) and, if applicable, an appropriate 
regulatory body. If a site has not been granted approval for RBR sampling, this section 
of the protocol will not be applicable at that site.
Sample Collection
The following samples will be collected for identification of dynamic (non-inherited) 
biomarkers:

Residual CSF samples

Plasma and serum samples

Whole Blood for RNA extraction 

Residual Skin tissue material
The following samples will be collected for identification of genetic (inherited) biomarkers:

Blood for DNA extraction

The sample collected for DNA extraction may be used for whole genome 
sequencing (WGS) and other genetic analysis and may be sent to one or more
laboratories for analysis.

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Genomics is increasingly informing researchers’ understanding of disease pathobiology. 
WGS provides a comprehensive characterization of the genome and, along with clinical 
data collected in this study, may increase the opportunity for developing new therapeutic 
approaches. Data will be analyzed in the context of this study but will also be explored in 
aggregate with data from other studies. The availability of a larger dataset will assist in 
identification of important pathways, guiding the development of new targeted agents.
For all samples, dates of consent and specimen collection should be recorded on the 
associated RBR page of the eCRF. For sampling procedures, storage conditions, and 
shipment instructions, see the separate laboratory manual.
RBR specimens will be stored and used until no longer needed or until they are 
exhausted. The Research Biosample Repository storage period will be in accordance 
with the IRB/EC‑approved Informed Consent Form and applicable laws (e.g., Health 
Authority requirements).
The repository specimens will be subject to the confidentiality standards (as described 
under Confidentiality and in Section 8.4.
Confidentiality
Data generated from RBR specimens must be available for inspection upon request by 
representatives of national and local Health Authorities, and monitors, representatives, 
and collaborators, as appropriate.
Participant medical information associated with RBR specimens is confidential and may 
only be disclosed to third parties as permitted by the Informed Consent Form (or 
separate authorization for use and disclosure of personal health information) signed by 
the participant, unless permitted or required by law.
Data derived from RBR specimen analysis on individual participants will generally not be 
provided to study investigators unless a request for research use is granted. The 
aggregate results of any conducted research will be available in accordance with the 
effective Roche policy on study data publication.
Genetic research data and associated clinical data may be shared with researchers who 
are not participating in the study or submitted to government or other health research 
databases for broad sharing with other researchers. Participants will not be identified by 
name or any other personally identifying information. Given the complexity and 
exploratory nature of these analyses, genetic data and analyses will not be shared with 
investigators or participants unless required by law.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR specimen data will become and remain the exclusive and 
unburdened property of Roche, except where agreed otherwise.

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Consent to Participate in the Research Biosample Repository
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR. The Investigator or authorized designee will explain to each participant the 
objectives, methods, and potential hazards of participation in the RBR. Participants will 
be told that they are free to refuse to participate and may withdraw their specimens at 
any time and for any reason during the storage period. A separate, specific signature will 
be required to document a participant’s agreement to provide optional RBR specimens. 
Participants who decline to participate will not provide a separate signature.
The Investigator should document whether or not the participant has given consent to 
participate by completing the RBR Sample Informed Consent eCRF.
In the event of death or loss of competence of a participant who is participating in the 
Research, the participant’s specimens and data will continue to be used as part of the 
RBR.
Withdrawal from the Research Biosample Repository
Participants who give consent to provide specimens for the RBR have the right to 
withdraw their specimens at any time for any reason. If a participant wishes to withdraw 
consent to the testing of his or her specimens, the Investigator must inform the Medical 
Monitor in writing of the participant’s wishes using the RBR Withdrawal Form and, if the 
trial is ongoing, must enter the date of withdrawal on the Research Biosample 
Repository Withdrawal of Informed Consent eCRF. The participant will be provided with 
instructions on how to withdraw consent after the trial is closed. A participant’s 
withdrawal from Study BP39529 does not, by itself, constitute withdrawal of specimens 
from the RBR. Likewise, a participant’s withdrawal from the RBR does not constitute 
withdrawal from Study BP39529. Data already generated before time of withdrawal of 
consent to Research Biosample Repository will still be used.
Monitoring and Oversight
Specimens collected for the Research Biosample Repository will be tracked in a manner 
consistent with Good Clinical Practice by a quality-controlled, auditable, and 
appropriately validated laboratory information management system, to ensure 
compliance with data confidentiality as well as adherence to authorized use of 
specimens as specified in this protocol and in the Informed Consent Form. Monitors and 
auditors will have direct access to appropriate parts of records relating to participant 
participation in Research Biosample Repository for the purposes of verifying the data 
provided to Roche. The site will permit monitoring, audits, IRB/EC review, and Health 
Authority inspections by providing direct access to source data and documents related to 
the samples.
4.6.2
Timing of Study Assessments
For a recommended sequence of assessments to be completed at each visit, see
Appendix 4.

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4.6.2.1
Screening and Pretreatment Assessments
Written informed consent for participation in the study must be obtained before 
performing any study‑specific screening tests or evaluations. Informed Consent Forms 
for enrolled participants and for participants who are not subsequently enrolled will be 
maintained at the study site.
All screening and pre-treatment assessments must be completed and reviewed to 
confirm that participants meet all eligibility criteria. The Investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or 
record reasons for screening failure.
An Eligibility Screening Form (ESF) documenting the Investigator’s assessment of each 
screened participant with regard to the protocol’s inclusion and exclusion criteria is to be 
completed by the Investigator and kept at the investigational site.
Screening and pre-treatment assessments must be performed within up to 56 days prior 
to Baseline/Day 1. The screening period may be extended by a maximum of 14 days 
upon consultation with the Sponsor/Medical Monitor.
Participants may be allowed to be rescreened, once upon approval from the Sponsor, for 
the following reasons:

In case of screen failure due to a transient abnormal laboratory or ECG result which 
is likely to normalize upon retesting or due to another reversible condition which 
does not compromise patient safety, screening can be repeated once with approval 
from the Sponsor. 

In case of screen failure due to a patient failed screening based on an 
inclusion/exclusion criterion which was updated in a protocol amendment, screening 
may be repeated if recruitment for the study is still ongoing.

In case of screen failure due to logistical, personal, or technical reasons for 
participants otherwise eligible. These reasons may include but are not limited to 
temporary site closure, scheduling visit delays due to the participant’s availability or 
delayed protocol-required central-read assessment results.
In case of rescreening, as a minimum, laboratory tests, physical examination and any 
screening tests which were not performed previously should be conducted. Repetition of 
other tests will require agreement between the Investigator and the Sponsor prior to 
rescreening. MRI, DaT-SPECT, skin biopsy and lumbar puncture will not be repeated.
4.6.2.2
Assessments during Treatment
Under no circumstances will participants who enroll in this study and have completed 
treatment as specified or withdraw from the study prematurely, be permitted to be 
allocated a new randomization number and re-enroll in the study.

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All assessments must be performed as per SoA (see Appendix 1, Appendix 2 and 
Appendix 3). Assessments scheduled on the day of study treatment administration 
should be performed prior to the administration, unless otherwise noted in the SoA. 
4.6.2.3
Assessments Prior to Start of Dopaminergic/Symptomatic PD 
Treatment
Participants who plan to start symptomatic treatment for PD (see Sections 4.5.2.1 and 
4.5.3) should complete the “prior to start of dopaminergic treatment” visit assessments 
(see Appendix 1, Appendix 2 and Appendix 3 for details), prior to the start of such 
treatment. Participants may continue in the study at their normal study visits.
4.6.2.4
Assessments at Study Completion/Early Termination Visit
Participants who complete the first two parts of the study (defined as completion of 
Week 104 visit) will be asked to return to the clinic 12 weeks7 days after the last dose 
of study treatment for a follow‑up visit. 
Participants who complete the all-on-treatment 5-year extension (defined as completion 
of Part 3 Week 260 visit) will be asked to return to the clinic 12 weeks 7 days after the 
last dose of study treatment for the Part 3 follow-up visit.
Participants who discontinue from the study early should complete the Early Termination 
assessments and return to the clinic 12 weeks7 days after the last dose of study 
treatment for the follow-up visit if they discontinue from Part 1 or Part 2 or for Part 3 
follow-up visit if they discontinue early from Part 3.
12-Week Treatment-free Follow-Up Assessments
After the treatment period is completed or participant withdraws from the study, the 
12-week treatment-free follow-up assessments provided in the SoA should be completed. 
After the study completion/early termination visit, adverse events should be followed as 
outlined in Sections 5.5 and 5.6.
4.6.2.5
Assessments at Unscheduled Visits
Assessments at unscheduled visits are based on the medical need of the patient. 
Assessments that are conducted at regular scheduled visits can be conducted at
unscheduled visits at the discretion of the Investigator.
4.7
PARTICIPANT, STUDY, AND SITE DISCONTINUATION
4.7.1
Study and Site Discontinuation
The Sponsor has the right to terminate this study at any time. Reasons for terminating 
the study may include, but are not limited to, the following:

The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to participants.

Participant enrollment is unsatisfactory.

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The Sponsor will notify the Investigator and Health Authorities if the study is placed on 
hold, or if the Sponsor decides to discontinue the study or development program.
The Sponsor has the right to close and replace (if required) a site at any time. Reasons 
may include, but are not limited to, the following:

Excessively slow recruitment

Poor protocol adherence

Inaccurate or incomplete data recording

Non-compliance with the International Conference on Harmonisation (ICH) guideline 
for Good Clinical Practice
4.7.2
Participant Discontinuation
The Investigator has the right to discontinue a participant from study treatment or 
withdraw a participant from the study at any time. In addition, participants have the right 
to voluntarily discontinue study treatment or withdraw from the study at any time for any 
reason. Reasons for discontinuation of study treatment or withdrawal from the study may 
include, but are not limited to, the following:

Participant withdrawal of consent at any time

Any medical condition that the Investigator or Sponsor determines may jeopardize 
the participant’s safety if he or she continues in the study

Investigator or Sponsor determines it is in the best interest of the participant

Participant non-compliance
4.7.2.1
Discontinuation from Study Treatment
Participant must discontinue study treatment if they experience any of the following:

Pregnancy
Participants who discontinue study treatment prematurely will be asked to return to the 
clinic for an early termination visit (see Section 4.6.2.4) and may undergo follow‑up 
assessments (Section 4.6.2.4). The primary reason for premature study treatment 
discontinuation should be documented on the appropriate eCRF. Participants who 
discontinue study treatment prematurely will not be replaced.
4.7.2.2
Withdrawal from Study
Every effort should be made to obtain information on participants who withdraw from the 
study. The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF.
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When a participant voluntarily withdraws from the study, or is withdrawn by the 
Investigator, samples collected until the date of withdrawal will be analyzed, unless 
participant specifically requests for these to be discarded or local laws require their 
immediate destruction. A participant’s withdrawal from Study BP39529 does not, by itself, 
constitute withdrawal of specimens donated to the Research Biosample Repository.
Participants who withdraw from the study for safety or for any other reason after 
receiving the first dose will not be replaced.
5.
ASSESSMENT OF SAFETY
5.1
SAFETY PARAMETERS AND DEFINITIONS
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and non-serious adverse events of special interest; 
measurement of protocol‑specified safety laboratory assessments; measurement of 
protocol-specified vital signs, ECGs, MRIs, and other protocol-specified tests that are 
deemed critical to the safety evaluation of the study.
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4.
5.1.1
Adverse Events
According to the ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product, regardless of causal attribution. An adverse event can therefore 
be any of the following:

Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.

Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition), except as described in 
Section 5.3.5.8.

Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline.

Any deterioration in a laboratory value or other clinical test (e.g., ECG, X‑ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug.

Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive 
procedures such as biopsies).

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5.1.2
Serious Adverse Events (Immediately Reportable to the 
Sponsor)
A serious adverse event is any adverse event that meets any of the following criteria:

Fatal (i.e., the adverse event actually causes or leads to death).

Life-threatening (i.e., the adverse event, in the view of the Investigator, places the 
patient at immediate risk of death)
This does not include any adverse event that had it occurred in a more severe form 
or was allowed to continue might have caused death.

Requires or prolongs inpatient hospitalization (see Section 5.3.5.10).

Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
functions).

Congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug.

Significant medical event in the Investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above).
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of 
an adverse event (rated as mild, moderate, or severe, or according to a pre-defined 
grading criteria (e.g., NCI CTCAE criteria; see Table 2 and Table 3); the event itself may 
be of relatively minor medical significance (such as severe headache without any further 
findings).
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF.
Serious adverse events are required to be reported by the Investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for 
reporting instructions).
5.1.3
Non-Serious Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor)
Non-serious adverse events of special interest are required to be reported by the 
Investigator to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2 for reporting instructions). Adverse events of special interest for 
this study include the following:

Cases of an elevated ALT or AST in combination with either an elevated bilirubin or 
clinical jaundice, as defined in Section 5.3.5.6.

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
Suspected transmission of an infectious agent by the study drug, as defined below:
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent. A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product. This term applies only
when a contamination of the study drug is suspected.
5.1.4
Selected Adverse Events
Additional data will be collected for the following selected adverse events:

Infusion-Related Reactions
Adverse events that occur during or within 24 hours after study drug administration 
and are judged to be related to study drug infusion should be captured as a 
diagnosis (e.g., “infusion-related reaction”) on the Adverse Event eCRF. Associated 
signs and symptoms should be recorded on the dedicated Infusion-Related 
Reaction eCRF. 
5.2
SAFETY PLAN
5.2.1
Management of Specific Adverse Events 
Infusion-related reactions (IRRs) have been reported with the use of biologic therapies, 
such as RO7046015. IRRs are usually reported with the first or second infusion of a 
therapeutic monoclonal antibody and tend to be dose-related. Such reactions typically 
occur during or shortly after an infusion or within 24 hours after study drug infusion. IRR 
symptoms may be indistinguishable from a Type 1 hypersensitivity reaction (i.e., flushing, 
rash, respiratory difficulty, hypotension, tachycardia); however, hypersensitivity reactions 
(IgE-mediated) generally do not occur with the first exposure to a biologic therapy. 
Specific management steps for IRRs and hypersensitivity reactions of different severity 
are provided in Table 1. The participant should be monitored until complete resolution of 
the symptoms and treated as clinically indicated. 

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Table 1
Guidelines for Managing IRRs
Event
Action to Be Taken
Infusion-related reaction
Grade 1
Stop or slow down study drug infusion to 50% of the initial rate. 
Assess vital signs. Clinical observation for improvement/resolution 
of symptoms. No treatment is needed. Participant may remain in 
the study.
Infusion-related reaction
Grade 2
Stop study drug infusion. Perform serial vital signs assessment 
every 15 minutes, supportive therapy (fluids [Normal Saline or 
Lactated Ringers], supplemental oxygen, diphenhydramine 
25 50mg PO or IV Q6h for rash, acetaminophen 650 mg PO [or 
minimum recommended adult dose of paracetamol]) Q6h. ADA 
and PK levels should be drawn if the event starts during the visit. If 
symptoms resolve completely during the visit, infusion may 
resume at 50% of the previous infusion rate. Participant may 
remain in the study and receive pre-medications of an 
antihistamine (loratadine 10 mg PO OR diphenhydramine 
25 50 mg as well as acetaminophen 650 mg [or minimum 
recommended adult dose of paracetamol] PO 30 60 minutes 
prior to subsequent doses, as per Principal Investigator’s [PI’s]
discretion).
Infusion-related reaction
Grade 3
Stop study drug infusion. Perform serial vital signs assessment as 
dictated by the patient’s clinical symptoms, supportive therapy 
(fluids [Normal Saline or Lactated Ringers], supplemental oxygen, 
diphenhydramine 25 50mg PO or IV for rash, acetaminophen 
650 mg PO [or minimum recommended adult dose of 
paracetamol], methylprednisolone 125 mg IV). Labs: Tryptase, 
cytokine panel, C3a, C5a within 3 hours of the event and to be 
repeated in 48 72 hours post event. ADA and PK levels should 
be drawn if the event starts during the visit and/or patient is 
hospitalized. Overnight inpatient observation per discretion of the 
PI. Future dosing plans can only be determined after the PI has 
had a discussion with the participant and Sponsor. 
Infusion-related reaction
Grade 4
Stop study drug infusion. Perform serial vital signs assessment 
every 5 minutes, supportive therapy (fluids [Normal Saline or 
Lactated Ringers], supplemental oxygen/ intubation and ventilatory 
support, diphenhydramine 25 50 mg PO or IV for rash, 
acetaminophen 650 mg PO [or minimum recommended adult dose 
of paracetamol], methylprednisolone 125 mg IV). Labs: tryptase, 
cytokine panel, C3a, C5a within 3 hours of the event and to be 
repeated in 48 72 hours post event. ADA and PK levels should 
be drawn. Discontinue patient from the study. Hospitalization for 
further evaluation and treatment.

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Table 1
Guidelines for Managing IRRs (cont.)
Event
Action to Be Taken
Anaphylaxis
Stop study drug infusion. Assess vital signs every 5 minutes. 
Administer IV fluids (Normal saline or Lactated Ringers), 
supplemental oxygen/ventilatory support, for systemic symptoms 
(angioedema, bronchospasm) epinephrine 1:1000, 0.3 mL 
subcutaneous (may be repeated in 20 minutes; in patients on beta 
blockers, glucagon administration may be needed), 
diphenhydramine 2550 mg IV, methylprednisolone 125 mg IV). 
Labs: tryptase, cytokine panel, C3a, C5a within 3 hours of the 
event and to be repeated in 4872 hours post-event. Discontinue 
patient from the study. ADA and PK levels should be drawn. 
Hospitalization for further observation and treatment. See 
Lieberman et al 2015 for anaphylaxis guidance. 
Figure 2 describes the process for the overall evaluation of AEs to determine whether an 
AE is an IRR.

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Figure 2
Evaluation and Reporting of Infusion Related Reactions (IRR)

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Figure 2
Evaluation and Reporting of Infusion Related Reactions (IRR) (cont.)

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The following guidelines are recommended for IRR grading:

For IRRs with onset during the infusion, refer to Table 2 - Infusion Related Reaction 
Grading  

For IRRs with onset within 24-hours after the end of the infusion,  refer to Table 3 -
Adverse Event Severity Grading
Table 2
Infusion-Related Reaction Grading
Grade
Infusion-Related Reaction
1
Mild transient reaction; Infusion interruption not indicated; Intervention not indicated.
2
Therapy or infusion interruption indicated but responds promptly to symptomatic 
treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); Prophylactic 
medications indicated for 24 hours.
3
Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief 
interruption of infusion); recurrence of symptoms following initial improvement; 
hospitalization indicated for clinical sequelae.
4
Life-threatening consequences; Urgent intervention indicated.
5
Death.
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or 
biological substances.
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events.
Note: Based on the NCI CTCAE (v4.03), which can be found at: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
5.3
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS
The Investigator is responsible for ensuring that all adverse events (see Section 5.1.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.4-5.6.
For each adverse event recorded on the Adverse Event eCRF, the Investigator will make 
an assessment of seriousness (see Section 5.1.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).
5.3.1
Adverse Event Reporting Period
Investigators will seek information on adverse events at each patient contact. All adverse 
events, whether reported by the patient or noted by study personnel, will be recorded in 
the participant’s medical record. Adverse events will then be reported on the Adverse 
Event eCRF as follows:
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention should be reported 
(e.g., serious adverse events related to invasive procedures such as biopsies). Any 
other adverse event should not be reported.

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After initiation of study drug, all adverse events, regardless of relationship to study 
drug, will be reported until 12 weeks after the last dose of study drug.
After a period of 12 weeks from the last dose of study drug, investigators should report 
any deaths, serious adverse events, or other adverse events of concern that are 
believed to be related to prior treatment with study drug (see Section 5.6).
5.3.2
Eliciting Adverse Event Information
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation time‑points. Examples of 
non-directive questions include the following:
“How have you felt since your last clinic visit?”
“Have you had any new or changed health problems since you were last here?”
5.3.3
Assessment of Severity of Adverse Events
Table 3 provides guidance for assessing adverse event severity.

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Table 3
Adverse Event Severity Grading Scale
Grade
Severity
1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
or intervention not indicated
2
Moderate; minimal, local, or non-invasive intervention indicated; or limiting 
age-appropriate instrumental activities of daily living a
3
Severe or medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; or 
limiting self-care activities of daily living b,c
4
Life-threatening consequences or urgent intervention indicated d
5
Death related to adverse event d
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events.
Note: Based on the NCI CTCAE (v4.03), which can be found at: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
a
Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc.
b
Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding one's self, using the toilet, and taking medications, as performed by patients who are 
not bedridden.
c
If an event is assessed as a "significant medical event," it must be reported as a serious 
adverse event (see Section 5.4.2 for reporting instructions), per the definition of serious adverse 
event in Section 5.1.2.
d
Grade 4 and 5 events must be reported as serious adverse events (see Section 5.4.2 for 
reporting instructions), per the definition of serious adverse event in Section 5.1.2.
5.3.4
Assessment of Causality of Adverse Events
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether or 
not an adverse event is considered to be related to the study drug, indicating "yes" or 
"no" accordingly. The following guidance should be taken into consideration:

Temporal relationship of event onset to the initiation of study drug

Course of the event, considering especially the effects of dose reduction or 
discontinuation of study drug

Known association of the event with the study drug or with similar treatments

Known association of the event with the disease under study

Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event

Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event

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5.3.5
Procedures for Recording Adverse Events
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF. Avoid colloquialisms and abbreviations.
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF.
5.3.5.1
Diagnosis versus Signs and Symptoms
Infusion-Related Reactions (IRRs)
Adverse events that occur during or within 24 hours after study drug administration and 
are judged to be related to study drug infusion should be captured as a diagnosis 
(e.g. “infusion-related reaction”) on the Adverse Event eCRF. Associated signs and 
symptoms should be recorded on the dedicated Infusion related-reaction eCRF. 
Other Adverse Events
For adverse events other than IRRs (see Section 5.3.5.1), a diagnosis (if known) should 
be recorded on the Adverse Event eCRF rather than individual signs and symptoms 
(e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases). However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded on the Adverse Event eCRF. If a diagnosis is 
subsequently established, all previously reported adverse events based on signs and 
symptoms should be nullified and replaced by one adverse event report based on the 
single diagnosis, with a starting date that corresponds to the starting date of the first 
symptom of the eventual diagnosis.
5.3.5.2
Adverse Events Occurring Secondary to Other Events
In general, adverse events occurring secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events. However, medically significant adverse events 
occurring secondary to an initiating event that are separated in time should be recorded 
as independent events on the Adverse Event eCRF. For example:

If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF.

If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF.

If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF.

If dizziness leads to a fall and subsequent fracture, all three events should be 
reported separately on the eCRF.
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated.

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5.3.5.3
Persistent or Recurrent Adverse Events
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation time‑points. Such events should only be recorded once on the 
Adverse Event eCRF. The initial severity of the event should be recorded, and the 
severity should be updated to reflect the most extreme severity any time the event 
worsens. If the event becomes serious, the Adverse Event eCRF should be updated to 
reflect this.
A recurrent adverse event is one that resolves between patient evaluation time‑points 
and subsequently recurs. Each recurrence of an adverse event should be recorded 
separately on the Adverse Event eCRF.
5.3.5.4
Abnormal Laboratory Values
Not every laboratory abnormality qualifies as an adverse event. A laboratory test result 
should be reported as an adverse event if it meets any of the following criteria:

Accompanied by clinical symptoms

Results in a change in study treatment (e.g., treatment interruption, or treatment 
discontinuation)

Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy

Clinically significant in the Investigator’s judgment
It is the Investigator’s responsibility to review all laboratory findings. Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event.
If a clinically significant laboratory abnormality is a sign of a disease or syndrome (e.g., 
alkaline phosphatase and bilirubin 5 times the upper limit of normal (ULN) associated 
with cholecystitis), only the diagnosis (i.e., cholecystitis) should be recorded on the 
Adverse Event eCRF.
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating if the test result is above or below the normal range (e.g., "elevated 
potassium", as opposed to "abnormal potassium"). If the laboratory abnormality can be 
characterized by a precise clinical term per standard definitions, the clinical term should 
be recorded as the adverse event. For example, an elevated serum potassium level of 
7.0 mEq/L should be recorded as “hyperkalemia”.
Observations of the same clinically significant laboratory abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens.

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5.3.5.5
Abnormal Vital Sign Values
Not every vital sign abnormality qualifies as an adverse event. A vital sign result should 
be reported as an adverse event if it meets any of the following criteria:

Accompanied by clinical symptoms

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation)

Results in a medical intervention or a change in concomitant therapy

Clinically significant in the Investigator’s judgment
It is the Investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event.
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF.
Observations of the same clinically significant vital sign abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens.
5.3.5.6
Abnormal Liver Function Tests
The finding of an elevated ALT or AST (3ULN) in combination with either an elevated 
total bilirubin (2ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury. 
Therefore, investigators must report as an adverse event the occurrence of either of the 
following:

Treatment-emergent ALT or AST3ULN in combination with total bilirubin 
2ULN

Treatment-emergent ALT or AST3ULN in combination with clinical jaundice
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.3.5.1) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or a non-serious adverse event of special 
interest (see Section 5.4.2).

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5.3.5.7
Deaths
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). 
Death should be considered an outcome and not a distinct event. The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF. Generally, only one such event should be reported. 
The term “sudden death” should only be used for the occurrence of an abrupt and 
unexpected death due to presumed cardiac causes in a patient with or without 
preexisting heart disease, within 1 hour of the onset of acute symptoms or, in the case of 
an unwitnessed death, within 24 hours after the patient was last seen alive and stable. If 
the cause of death is unknown and cannot be ascertained at the time of reporting, 
“unexplained death” should be recorded on the Adverse Event eCRF. If the cause of 
death later becomes available (e.g., after autopsy), “unexplained death” should be 
replaced by the established cause of death.
5.3.5.8
Preexisting Medical Conditions
A preexisting medical condition is one that is present at the screening visit for this study. 
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF.
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study. When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., “more frequent headaches”).
5.3.5.9
Lack of Efficacy or Worsening of Parkinson’s Disease
Medical occurrences or symptoms of deterioration that are anticipated as part of PD 
progression will generally be recorded by means of the efficacy assessment 
(MDS-UPDRS). 
If judged by the Investigator to have unexpectedly worsened in severity or frequency or 
changed in nature of PD at any time during the study, it would then be important to 
report an unanticipated worsening of PD as an Adverse Event eCRF and convey the 
concept that the condition has changed by including applicable descriptors 
(e.g., “accelerated PD”).
5.3.5.10
Hospitalization or Prolonged Hospitalization
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event (per the definition of serious 
adverse event in Section 5.3.5.10), except as outlined below.

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The following hospitalization scenarios are not considered to be serious adverse events:

Hospitalization for a preexisting condition, provided that all of the following criteria 
are met:
–
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of a disease.
–
The participant has not suffered an adverse event
5.3.5.11
Overdoses and Medication Errors
Study drug overdose is the accidental or intentional use of the drug in an amount higher 
than the dose being studied. Medication error is the accidental deviation in the 
administration of a drug. In some cases, a medication error may be intercepted prior to 
administration of the drug.
An overdose or incorrect administration of study drug is not an adverse event unless it 
results in untoward medical effects.
Any study drug overdose or incorrect administration of study drug should be noted on 
the Study Drug Administration eCRF.
All adverse events associated with an overdose or incorrect administration of study drug 
should be recorded on the Adverse Event eCRF. If the associated adverse event fulfills 
serious criteria, the event should be reported to the Sponsor immediately (i.e., no more 
than 24 hours after learning of the event; see Section 5.4.2).
5.3.5.12
Patient-Reported Outcome Data
Adverse event reports will not be derived from PRO data. However, if any patient 
responses suggestive of a possible adverse event are identified during site review of the 
PRO questionnaires, site staff will alert the Investigator, who will determine if the criteria 
for an adverse event have been met and will document the outcome of this assessment 
in the participant's medical record per site practice. If the event meets the criteria for an 
adverse event, it will be reported on the Adverse Event eCRF.
5.4
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial. The Investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the Investigator learns of the event. The following is a list 
of events that the Investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study treatment:

Serious adverse events

Non-serious adverse events of special interest

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
Pregnancies
The Investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the
information). New significant information includes the following:

New signs or symptoms or a change in the diagnosis

Significant new diagnostic test results

Change in causality based on new information

Change in the event’s outcome, including recovery

Additional narrative information on the clinical course of the event
Investigators must also comply with local requirements for reporting serious adverse 
events to the local Health Authority and IRB/EC.
5.4.1
Emergency Medical Contacts
To ensure the safety of study patients, access to the Medical monitors is available 
24 hours a day 7 days a week. Medical monitors’ contact details will be available on a 
separate list generated by the study management team.
5.4.2
Reporting Requirements for Serious Adverse Events and 
Non-Serious Adverse Events of Special Interest
5.4.2.1
Events That Occur prior to Study Drug Initiation
After informed consent has been obtained but prior to initiation of study treatment, only 
serious adverse events caused by a protocol-mandated intervention should be reported. 
The Serious Adverse Event/Adverse Event of Special Interest Reporting Form provided 
to investigators should be completed and submitted to the SAE Responsible immediately 
(i.e., no more than 24 hours after learning of the event).
5.4.2.2
Events That Occur after Study Drug Initiation
For reports of serious adverse events and non-serious adverse events of special interest 
(see Sections 5.1.2 and 5.1.3) that occur after initiation of study treatment, investigators 
should record all case details that can be gathered immediately (i.e., within 24 hours 
after learning of the event) on the appropriate Serious Adverse Event / Adverse Event of 
Special Interest eCRF form and submit the report via the electronic data capture (EDC) 
system. A report will be generated and sent to the Sponsor’s Safety Risk Management 
department.
In the event that the EDC system is unavailable, the Serious Adverse Event/Adverse 
Event of Special Interest Reporting Form provided to investigators should be completed 
and submitted to the SAE Responsible immediately (i.e., no more than 24 hours after 
learning of the event).

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Once the EDC system is available, all information will need to be entered and submitted 
via the EDC system.
5.4.3
Reporting Requirements for Pregnancies
5.4.3.1
Pregnancies in Female Participants
Female participants of childbearing potential will be instructed to immediately inform the 
Investigator if they become pregnant during the study or within 12 weeks after the last 
dose of study drug. A Clinical Trial Pregnancy Reporting Form should be completed by 
the Investigator and submitted to the Sponsor within 24 hours after learning of the 
pregnancy. Pregnancy should not be recorded on the Adverse Event eCRF. The 
Investigator should discontinue RO7046015 and counsel the patient, discussing the risks 
of the pregnancy and the possible effects on the fetus. Monitoring of the participant 
should continue until conclusion of the pregnancy.
5.4.3.2
Pregnancies in Female Partners of Male Participants
Male participants will be instructed through the Informed Consent Form to immediately 
inform the Investigator if their partner becomes pregnant during the study or within 
12 weeks after the last dose of study drug. A Clinical Trial Pregnancy Reporting Form 
should be completed by the Investigator and submitted to the Sponsor within 24 hours 
after learning of the pregnancy. Attempts should be made to collect and report details of 
the course and outcome of any pregnancy in the partner of a male participant exposed 
to study treatment. The pregnant partner will need to sign an Authorization for Use and 
Disclosure of Pregnancy Health Information to allow for follow-up on her pregnancy. 
Once the authorization has been signed, the Investigator will update the Clinical Trial 
Pregnancy Reporting Form with additional information on the course and outcome of the 
pregnancy. An Investigator who is contacted by the male participant or his pregnant 
partner may provide information on the risks of the pregnancy and the possible effects 
on the fetus, to support an informed decision in cooperation with the treating physician 
and/or obstetrician.
5.4.3.3
Abortions
Any spontaneous abortion should be classified as a serious adverse event (as the 
Sponsor considers spontaneous abortions to be medically significant events), recorded 
on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more 
than 24 hours after learning of the event; see Section 5.4.2).
Any induced abortion due to maternal toxicity and/or embryo-fetal toxicity should also be 
classified as serious adverse event, recorded on the Adverse Event eCRF, and reported 
to the Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2).
Elective abortion not associated with toxicity (e.g., induced abortion for personal reasons) 
does not require expedited reporting but should be reported as outcome of pregnancy on 
the Clinical Trial Pregnancy Reporting Form.

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5.4.3.4
Congenital Anomalies/Birth Defects
Any congenital anomaly/birth defect in a child born to a female participant or female 
partner of a male participant exposed to study drug should be classified as a serious 
adverse event, recorded on the Adverse Event eCRF, and reported to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2).
5.5
FOLLOW-UP OF PARTICIPANTS AFTER ADVERSE EVENTS
5.5.1
Investigator Follow-Up
The Investigator should follow each adverse event until the event has resolved to 
baseline grade or better, the event is assessed as stable by the Investigator, the 
participant is lost to follow-up, or the participant withdraws consent. Every effort should 
be made to follow all serious adverse events considered to be related to study drug or 
trial-related procedures until a final outcome can be reported.
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the participant’s medical record to facilitate source 
data verification. If, after follow-up, return to baseline status or stabilization cannot be 
established, an explanation should be recorded on the Adverse Event eCRF.
All pregnancies reported during the study should be followed until pregnancy outcome 
and reported according to the instructions provided in Section 5.4.2.1.
5.5.2
Sponsor Follow-Up
For serious adverse events, non-serious adverse events of special interest, and 
pregnancies, the Sponsor or a designee may follow up by telephone, fax, electronic mail, 
and/or a monitoring visit to obtain additional case details and outcome information 
(e.g., from hospital discharge summaries, consultant reports, autopsy reports) in order to 
perform an independent medical assessment of the reported case.
5.6
POST-STUDY ADVERSE EVENTS
The Investigator is not required to actively monitor participants for adverse events after 
the end of the adverse event reporting period (defined as 12 weeks after the last dose of 
study treatment). 
If the Investigator becomes aware of any other serious adverse event occurring after the 
end of the adverse event reporting period, if the event is believed to be related to prior 
study treatment, the event should be reported directly to the Sponsor or its designee, 
either by faxing or by scanning and emailing the Serious Adverse Event Reporting Form 
using the fax number or email address provided to investigators. 

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5.7
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES
The Sponsor will promptly evaluate all serious adverse events and non-serious adverse 
events of special interest against cumulative product experience to identify and 
expeditiously communicate possible new safety findings to investigators, IRBs, ECs, and 
applicable health authorities based on applicable legislation.
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events using the following reference document:

RO7046015 Investigator's Brochure
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document.
Reporting requirements will also be based on the Investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed.
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN
6.1
DETERMINATION OF SAMPLE SIZE
A sample size of 100 randomized participants per group (300 participants for the three 
groups) has been chosen to obtain a power of approximately 80% at two-sided -level of 
20% (which corresponds to a one-sided -level of 10%) for the pairwise comparison of 
each active dose arm to placebo. The power calculation was based on simulations of the 
mixed-effect model repeated measures (MMRM) analysis planned for the primary 
efficacy variable. Assessments performed while on any symptomatic treatment started 
after randomization will not be included in the analysis. The following assumptions were 
made for simulating the data:

Seven post-baseline assessment visits,

An overall rate of missing values (due to participants starting symptomatic therapy 
or prematurely withdrawing from study medication during the 52-week 
placebo-controlled treatment period) of 25% in the placebo group and 20% in each 
dose group at Week 52, with incremental rates over the 52-week placebo-controlled 
period

A linear mean increase of the primary endpoint (natural progression) of 
eight points/year for the placebo arm, with a linearly increasing common standard 
deviation reaching nine points at Week 52

An effect size of 0.33 (difference3 points, relative reduction of progression37.5%) 
for one dose group versus placebo at Week 52 with increasing magnitude of 
treatment difference over the placebo-controlled period

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
A compound symmetry correlation structure assuming a correlation coefficient of 
0.55 between different visits.
Table 4 provides the additional information needed to perform the simulations.
Table 4
Assumptions Used for Simulations
Post-Baseline Visit (weeks)
8
16
24
32
40
48
52
Change from baseline in MDS-UPDRS total, placebo 
arm (points)
1.2 
2.4 
4 
4.8 
6
7.2
8
Change from baseline in MDS-UPDRS total, active 
treatment arm (points)
0.8 
1.5 
2.5 3.0 3.8
4.5
5
Common standard deviation for change from baseline 
in MDS UPDRS total (points)
6.75 7.25 7.75 
8 
8.5
8.75
9
Percentage of patients with non-evaluable data, 
placebo*
1%
3%
5%
7% 17% 22% 25%
Percentage of patients with non-evaluable data, 
treatment*
1%
3%
5%
7% 12% 17% 20%
*Includes data from patients that prematurely dropped out from the study and/or started 
symptomatic therapy after randomization.
The assumptions on progression, variability, dropout rate and likelihood to start 
symptomatic therapy within the first 52 weeks of treatment, with or without a MAO-B 
inhibitor as background therapy, were derived from analyses based on the PPMI 
database (Marek et al 2011, Simuni et al 2015) and various sources of information from 
the literature.
The sample size of 100 patients per arm also provides 76% power (20%, two-sided
or 10%, one-sided) to demonstrate a 37.5% reduction (effect size 0.318 based on 
assumption of decline over 52 weeks of 0.157 for the placebo arm and standard 
deviation of 0.185 derived from the PPMI database) for the key secondary endpoint, the 
DaT-SPECT signal loss at Week 52, for the pairwise comparison of each active dose 
arm to placebo. The missing values assumption used was 15% and included participants 
who withdrew from study medication before Week 52 or who did not have a valid DaT-
SPECT assessment at Week 52. Assessments performed while on any symptomatic 
treatment started after randomization will not be excluded from the analysis.
No adjustments for multiple comparisons were incorporated into the analyses.

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The sample size may be adjusted depending on the outcome of the iDMC review 
performed during the study. If the enrollment to the high dose is stopped and a new dose 
is introduced as advised by the iDMC, the Sponsor may propose the enrolment of (up to) 
an additional 20% of patients, see Section 3.1.2.1. The aim of this increase in sample 
size would be to ensure a power of approximately 80% at two-sided -level of 20% 
(corresponding to a one-sided -level of 10%) for the pairwise comparison of the new 
dose arm to the placebo group consisting of participants randomized after the decision 
to include the new dose arm. 
The sample size may also be adjusted if the initial assumptions on dropout rate and 
likelihood to start dopaminergic therapy as described in Table 4 are different from the 
actual values observed. If that is the case, the Sponsor may increase enrolment up to 20% 
of the total sample size. The aim of this increase in sample size is to ensure that the 
pairwise comparison of each active dose arm to placebo remains adequately powered.
6.2
SUMMARIES OF CONDUCT OF STUDY
To determine whether the integrity of the study was maintained, listings/summaries of 
data referring to the general conduct of the study (such as enrollment, protocol violations, 
use of prohibited co-medication, blinding details) will be generated.
6.3
ANALYSIS POPULATIONS
6.3.1
Safety Analysis Population
All randomized participants receiving any amount of the study drug will be included in 
the safety analysis. Patients who received any randomized treatment other than that to 
which they were randomized will be analyzed according to the treatment actually 
received.
6.3.2
Efficacy Analysis Populations
The modified intent-to-treat (mITT) population is defined as consisting of all participants 
randomized, who received any amount of the study treatment, participants will be 
grouped according to which treatment they were randomized.
6.3.3
Immunogenicity Analysis Population
Participants who had at least one pre-dose and one post-dose ADA assessment will be 
included and analyzed according to the RO7046015 dose they actually received. Only 
samples from RO7046015-treated participants will be analyzed (see Section 4.6.1.7).
6.3.4
Pharmacokinetic Analysis Population
All participants providing pharmacokinetic data will be included in the PK Analysis 
Population. Subjects may be excluded from the PK Analysis Population if, for example, 
data are unavailable or incomplete which may influence the pharmacokinetic analysis. 
This will be precisely defined in the statistical analysis plan. Excluded cases will be 
documented together with the reason for exclusion.

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6.4
SUMMARIES OF TREATMENT GROUP COMPARABILITY
Demographics, baseline characteristics and all baseline laboratory values will be 
summarized descriptively by treatment using frequency tables and summary statistics as 
appropriate. 
Baseline assessments will be defined in the Statistical Analysis Plan.
6.5
SAFETY ANALYSES
All safety analyses will be based on the safety analysis population, defined in 
Section 6.3.1.
As appropriate, listings, summary tables and graphs will be provided for safety and 
tolerability assessments, including:

Incidence of AEs (overall, by intensity and by relationship to study medication).

Incidence of SAEs.

Incidence of laboratory abnormalities (including hematology, clinical chemistry, 
coagulation, and urinalysis parameters).

Incidence of BP abnormalities.

Incidence of ECG abnormalities (including changes from baseline).

Incidence of MRI abnormalities (changes from baseline only). 

Incidence of ADAs.

C-SSRS (per visit).
Further details on the safety parameters are given in Section 5.1. Safety data will be 
summarized using descriptive statistics. 
6.5.1
Adverse Events
The original terms recorded on the eCRF by the Investigator for adverse events will be 
standardized by the Sponsor.
Adverse events will be summarized by mapped term and appropriate thesaurus level.
6.5.2
Clinical Laboratory Test Results
All clinical laboratory data will be stored on the database in the units in which they were 
reported. Participant listings and summary statistics at each assessment time will be 
presented using the International System of Units (SI units; Système International 
d’Unités). Laboratory data not reported in SI units will be converted to SI units before 
processing.
Laboratory test values will be presented by individual listings with flagging of values 
outside the normal ranges.

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6.5.2.1
Standard Reference Ranges and Transformation of Data
Roche standard reference ranges, rather than the reference ranges of the investigator, 
will be used for all parameters. For most parameters, the measured laboratory test result 
will be assessed directly using the Roche standard reference range. Certain laboratory 
parameters will be transformed to Roche’s standard reference ranges.
A transformation will be performed on certain laboratory tests that lack sufficiently 
common procedures and have a wide range of investigator ranges, e.g., enzyme tests 
that include AST, ALT, and alkaline phosphatase and total bilirubin. Since the standard 
reference ranges for these parameters have a lower limit of zero, only the upper limits of 
the ranges will be used in transforming the data.
6.5.2.2
Definition of Laboratory Abnormalities
For all laboratory parameters included, there exists a Roche predefined standard 
reference range. Laboratory values falling outside this standard reference range will be 
labeled “H” for high or “L” for low in patient listings of laboratory data.
In addition to the standard reference range, a marked reference range has been 
predefined by Roche for each laboratory parameter. The marked reference range is 
broader than the standard reference range. Values falling outside the marked reference 
range that also represent a defined change from baseline will be considered marked 
laboratory abnormalities (i.e., potentially clinically relevant). If a baseline value is not 
available for a patient, the midpoint of the standard reference range will be used as the 
Patient’s baseline value for the purposes of determining marked laboratory 
abnormalities. Marked laboratory abnormalities will be labeled in the patient listings as 
“HH” for very high or “LL” for very low.
6.5.3
Vital Signs
Vital signs data will be presented by individual listings with flagging of values outside the 
normal ranges and flagging of marked abnormalities (these will be precisely defined in 
the statistical analysis plan). In addition, tabular summaries will be used, as appropriate.
6.5.4
ECG Data Analysis
ECG data will be presented by individual listings with flagging of values outside the 
normal ranges and flagging of marked abnormalities (these will be precisely defined in 
the statistical analysis plan). In addition, tabular summaries will be used, as appropriate.
The standard deviation of the RR interval for the individual participant may be assessed 
as an exploratory endpoint, as studies (unpublished data) have reported signs of 
autonomic dysfunction in patients with PD. This may be a potential prodromal marker or 
marker of a subtype of PD.

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6.5.5
Concomitant Medications
The original terms recorded on the participants’ eCRF by the Investigator for 
concomitant medications will be standardized by the Sponsor by assigning preferred 
terms.
Concomitant medications will be presented in summary tables and listings.
6.6
EFFICACY ANALYSES
The primary analysis population for all efficacy analyses will be based on the modified 
ITT population, as defined in Section 6.3.2.
Analyses of efficacy endpoints (primary, secondary, and exploratory) will include the 
following covariates in the model:

Treatment: placebo, RO7046015 high dose (4500 mg and 3500 mg) and 
RO7046015 low dose (1500 mg).

Background therapy at baseline (MAO-B inhibitor treatment): Yes or No.

Age group: < 60 years vs 60 years.

Sex: male or female.

DaT-SPECT ipsilateral (to the clinically dominant side) putamen binding ratio at 
baseline.
For each continuous endpoint the baseline of the endpoint will also be included in the 
model.
In addition to the analyses described in Sections 6.6.1 and 6.6.2, the following analyses 
will be performed for the primary efficacy endpoint and secondary efficacy endpoints, 
respectively. Additional details of these analyses will be described in the statistical 
analysis plan:

Sensitivity analyses to evaluate the robustness of results to the primary analysis 
methods:
–
The analysis of the primary endpoint (change in MDS-UPDRS total score) and 
change in MoCA will be repeated including only patients who completed Part 1 
without starting symptomatic PD treatment

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–
The analysis of the primary endpoint of MDS-UPDRS total score (sum of Parts I, 
II, and III) will also be repeated using a baseline value calculated for each 
patient as the average of pre-treatment values of the MDS-UPDRS total score 
(sum of Parts I, II, and III), as the average of screening and Day 1 values).  
(The primary endpoint and the MoCA will be re-analyzed by only including 
patients who completed Part 1 without starting symptomatic PD treatment; the 
primary endpoint of MDS-UPDRS total score (sum of Parts I, II, and III) will be 
re-analyzed by calculating for each patient the baseline value as the average of 
pre-treatment values of the MDS-UPDRS total score (sum of Parts I, II, and III), 
i.e. the average of screening and Day 1)

Subgroup analyses to evaluate the consistency of results across pre-specified 
subgroups:
–
MAO-B Inhibitors at baseline (yes vs. no)
–
Hoehn &Yahr stage (1 vs. 2), 
–
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) (RBDSQ < 5 
vs 5), 
–
Alpha-synuclein pathology in peripheral nerves from  skin biopsies (positive vs. 
negative) 
–
DaT-SPECT (very abnormal vs. abnormal).
–
Data-driven sub-phenotypes (diffuse malignant vs. mild motor-predominant vs. 
intermediate)
For the derivations of the data-driven sub-phenotypes, scales are classified into 
motor and non-motor. The motor scales are UPDRS-Part II (Motor symptoms) 
and UPDRS-Part III (Motor signs). The non-motor scales are SCOPA-AUT, 
RDBSQ and MOCA. After each one of the scales have been divided into 
percentiles, the data-driven sub-phenotypes are defined as follows:
o
Diffuse malignant: either motor score greater than the 75th percentile 
AND at least 1 non-motor score greater than the 75th percentile OR all 
3 non-motor scores greater than the 75th percentile
o
Mild motor-predominant: Motor and all non-motor scores less than the 
75th percentile
o
Intermediate: All those individuals not meeting criteria for other subtypes
The efficacy analyses will include all enrolled patients and will be presented separately
for Part 1, Part 2, and Part 3 of the study. All additional statistical details for the efficacy 
analyses will be documented in the Statistical Analysis Plan (SAP).
6.6.1
Primary Efficacy Endpoint
The primary efficacy endpoint is the change in total MDS-UPDRS (sum of Parts I, II and 
III) from baseline to Week 52 (end of Part 1 of the study). 

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The primary efficacy endpoint will be analyzed using a MMRM with the covariates 
described in Section 6.6 and visit (seven levels) as fixed effects, treatment-by-visit 
interaction term, and the baseline value for total MDS-UPDRS (sum of Parts I, II and III) 
as a covariate; an interaction term between baseline MDS-UPDRS by visit will also be 
included. Within each participant, the model will incorporate an unstructured variance-
covariance matrix for the random error terms. Observations from different participants 
are considered independent. For each active dose arm tested at the final analysis, this 
model will be used to test the null hypothesis of no treatment difference between the 
placebo arm and each active arm at a two-sided -level of 20%, which corresponds to a 
one-sided -level of 10%. 
Starting symptomatic PD treatment for the statistical analysis is defined as starting 
COMT inhibitors (entacapone, tolcapone), amantadine, anticholinergics, levodopa, 
dopamine agonists, or MAOB inhibitors and - for patients already on MAO-B inhibitors at 
baseline - also increases in dose or regimen of the MAOB inhibitor. Assessments 
performed after starting symptomatic PD treatment will not be included in the primary 
analysis. 
Missing values will be handled via the MMRM methodology.
The primary endpoint will also be summarized using descriptive statistics.
6.6.2
Secondary Efficacy Endpoints
For the endpoints of MDS-UPDRS Part IA, Part IB, Part I total, Part II total, Part III total, 
and Part III subscores, CGI-I, and PGI-C the information collected after symptomatic PD 
treatment or after an increase in MAO-B inhibitor therapy will be handled as in the 
primary analysis. The analysis of all other secondary endpoints will include all the 
information available regardless of start of symptomatic PD treatment.  
An important biomarker secondary endpoint is the change (between baseline and the 
Week 52 visit) in DaT-SPECT uptake values in the ipsilateral putamen, which will be 
analyzed via an analysis of covariance (ANCOVA), regardless of intake of symptomatic 
PD therapy during the first 52 weeks. The model will include the covariates described in 
Section 6.6 as main effects. There will be no imputation for missing values.
Other secondary endpoints, which will also be analyzed at the end of Part 1 (after 
52 weeks of treatment with either placebo or active treatment) include:

Change in MDS-UPDRS sub-scores from baseline to Week 52 for Part IA, Part IB, 
Part I total, Part II total, Part III total, and Part III subscores (bradykinesia, resting 
tremor and axial symptoms) analyzed with exactly the same MMRM approach as for 
the primary endpoint. 

Change in MoCA total score from baseline to Week 52 analyzed with an analysis of 
covariance (ANCOVA).

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
CGI-I will be analyzed using a logistic regression model, including the covariates 
described in Section 6.6. 

PGI-C will be analyzed using a logistic regression model, including the covariates 
described in Section 6.6.

Change in Schwab and England Activities of Daily Living (SE-ADL) from baseline to 
Week 52 will be analyzed with ANCOVA.

Time to first occurrence of either of the following: 3 points change from baseline in
MDS-UPDRS Part I, or 3 points change from baseline in MDS-UPDRS Part II will 
be analyzed with a Cox proportional hazards model including the covariates 
described in Section 6.6, along with a Kaplan-Meier plot.

Time to start of dopaminergic (levodopa or dopamine agonists) treatment will be 
analyzed with a Cox proportional hazards model including the covariates described 
in Section 6.6, along with a Kaplan-Meier plot. Events in this analysis will only 
consider the start of levodopa or dopamine agonist.
All secondary endpoints will also be summarized using descriptive statistics.
6.7
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES
Non-linear mixed effects modelling (with software NONMEM [Beal and Sheiner 1998]) 
will be used to analyze the sparse sampling dose-concentration-time data of 
RO7046015. Population and individual pharmacokinetic parameters (e.g., CL and 
central volume) will be estimated and the influence of various covariates (such as age, 
sex and body weight) on these parameters will be investigated. The data collected 
during the study will be pooled with data collected in the previous Phase I studies 
conducted in healthy volunteers and patients with PD. Secondary PK parameters such 
as AUC, Cmax and Ctrough at steady state will be derived from the individual post-hoc 
predictions.
Graphical exploration of the relationship between RO7046015 concentrations and 
MDS-UPDRS Total Score (sum of Parts I, II and III), other selected clinical endpoints, 
biomarkers and safety endpoints will be performed. If indicated by such exploration, 
more formal analyses of the PK/PD relationship using non-linear mixed effects modelling 
method will be undertaken.
In-house analysis to build a disease progression model was performed using the PPMI 
MDS-UPDRS Total Score (sum of Parts I, II and III). This model will serve as the basis 
for the development of the disease progression model using placebo data. Potential 
disease-modifying effect of RO7046015 will be explored. For the investigation of the 
drug effect, classical hierarchical PK/PD models like linear, Emax or sigmoidal Emax
models will be tested. The possibility of a delay between the time-course of exposure 
and effects will be investigated using indirect pharmacodynamic models or using an 
effect compartment.

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Details of the modelling analyses will be described in a Modelling and Simulation 
Analysis Plan. The results will be reported in a document separate from the clinical study 
report.
6.8
EXPLORATORY ANALYSES
The exploratory analysis may be done for the outcome measures described in 
Section 3.3.4. 
If applicable, exploratory endpoints may be analyzed with the following methods:

Continuous endpoints via ANCOVA and/or MMRM. 

Time-to-event data via Kaplan-Meier Plot and Cox proportional hazards model.

Ordered categorical data (e.g., individual MDS-UPDRS items) via Wilcoxon rank 
sum test.

Binary data (such as responder analyses) via logistic regression.
In addition the following exploratory analysis may also be done: 

Slope analyses comparing treatment groups (e.g., placebo – high-dose vs 
high dose high dose) within Part 2 in order to explore the disease-modifying effect 
of the drug.

MDS-UPDRS total at Week 52 analyzed via a disease-modelling approach 
(e.g., Holford) with parametrization accounting for possible symptomatic and 
disease modifying effect of the drug.

Pooled active treatment doses compared to placebo.

Relation between alpha-synuclein pathology assessed by the skin biopsy results 
and DaT-SPECT (both randomized and screen failures).

Random coefficients model for the analysis of dBM endpoints.
The exploration of a disease model analysis to identify a potential disease modifying 
effect is described in Section 6.7.
Item response theory (IRT) can permit a more precise analysis by integrating the whole 
available items information and increase the probability to detect changes due to a drug 
effect (Ueckert 2014). Therefore, IRT has the potential to increase the sensitivity for 
assessing effects using the composite endpoint MDS-UPDRS and to detect a drug effect 
acting on the disease progression. 
A baseline IRT model was built to analyze the baseline data in de novo patients from the 
PPMI database (Buatois et al 2015, Buatois et al 2016). It will be combined with 
longitudinal models for placebo and drug effect for which parameters will be estimated 
using the RO7046015 data.

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The results of the IRT analysis will be reported in a document separate from the clinical 
study report.
6.9
EFFICACY INTERIM ANALYSES
An efficacy interim analysis may be conducted as described in Section 3.1.2.2.  
In addition to the primary analysis performed at Week 52, the Sponsor may choose to 
conduct additional interim efficacy analyses during Part 2 and/or Part 3 of the 
trial. The decision to conduct an optional interim analysis and the timing of the 
analysis will be documented in the Sponsor’s trial master file prior to the conduct of the 
interim analysis. The interim analysis will be performed and interpreted by Sponsor 
study team personnel.
7.
DATA COLLECTION AND MANAGEMENT
7.1
DATA QUALITY ASSURANCE
The Sponsor will be responsible for data management of this study, including quality 
checking of the data. Sites will be responsible for data entry into the Electronic Data 
Capture (EDC) system.
A comprehensive validation check program will verify the data. Discrepancies will be 
generated automatically in the system at the point of entry or added manually for 
resolution by the investigator or the Monitors.
The Sponsor will produce a Data Handling Manual and Data Management Plan that 
describes the quality checking to be performed on the data. Central laboratory data and 
other electronic data will be sent directly to the Sponsor, using the Sponsor’s standard 
procedures to handle and process the electronic transfer of these data.
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor’s standard procedures.

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7.2
ELECTRONIC CASE REPORT FORMS 
Data for this study will be captured via an on line EDC system. The data collected in the 
source documents is entered onto the study eCRF. An audit trail will maintain a record of 
initial entries and changes made; reasons for change; time and date of entry; and user 
name of person authorizing entry or change. For each participant screened and enrolled 
or not, an eCRF must be completed and electronically signed by the Principal 
Investigator or authorized delegate from the study staff. If a participant withdraws from 
the study, the reason must be noted on the eCRF. If a participant is withdrawn from the 
study because of a treatment‑limiting adverse event, thorough efforts should be made to 
clearly document the outcome.
The Investigator should ensure the accuracy, completeness and timeliness of the data 
reported to the Sponsor in the eCRFs and in all required reports.
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor.
At the end of the study, the Investigator will receive participant data for his or her site in 
a readable format on a compact disc that must be kept with the study records. 
Acknowledgement of receipt of the compact disc is required.
7.3
DIGITAL BIOMARKER DATA
During “Active Tests” and “Passive Monitoring”, the phone and wrist-worn wearable 
record movement and location data. Data on the technical status of the devices is also 
recorded. Participants can choose to pause location data recording. No patient 
identifiable information is stored on the devices. For selected “Active Test” tasks, touch 
and sound is also recorded. Video is not recorded.
Digital Biomarker Data are encrypted and uploaded to secure servers whenever the 
phone is connected to WIFI. If participants have a WIFI network at home, they are 
encouraged to connect their smartphone to enable data transfer. If no WIFI network is 
available, the sensor data will be transferred during site visits or after the devices have 
been returned.
All Digital Biomarker data will be managed by the Sponsor who will monitor and ensure 
the integrity and quality of the acquired data. This includes but is not limited to the 
analysis of sensor data together with basic demographic data (such as sex, year of birth, 
weight, height) and MDS-UPDRS data.
7.4
SOURCE DATA DOCUMENTATION
Study monitors will perform ongoing source data verification to confirm that critical 
protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are 
accurate, complete, and verifiable from source documents.

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Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time. They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, patient-reported outcomes, 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X‑rays, 
patient files, and records kept at pharmacies, laboratories, and medico‑technical  
departments involved in a clinical trial.
Before study initiation, data to be entered directly into the eCRFs (i.e., no prior written or 
electronic record of the data) and considered source data must be defined in the Trial 
Monitoring Plan.
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.6.
To facilitate source data verification, the investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial‑related 
monitoring, Sponsor audits, and IRB/EC review. The investigational site must also allow 
inspection by applicable health authorities.
7.5
USE OF COMPUTERIZED SYSTEMS
When clinical observations are entered directly into an investigational site’s 
computerized medical record system (i.e., in lieu of original hardcopy records), the 
electronic record can serve as the source document if the system has been validated in 
accordance with Health Authority requirements pertaining to computerized systems used 
in clinical research. An acceptable computerized data collection system allows 
preservation of the original entry of data. If original data are modified, the system should 
maintain a viewable audit trail that shows the original data as well as the reason for the 
change, name of the person making the change, and date of the change.
7.6
RETENTION OF RECORDS
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, ePRO data (if applicable), Informed Consent Forms, laboratory 
test results, and medication inventory records, must be retained by the Principal 
Investigator for at least 15 years after completion or discontinuation of the study, or for 
the length of time required by relevant national or local Health Authorities, whichever is 
longer. After that period of time, the documents may be destroyed, according to local 
regulations. No records may be disposed of without the written approval of the Sponsor. 
Written notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location.

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Audio files collected as part of digital Biomarker assessments will be retained for the full 
retention period of at least 15 years.
Video files collected for MDS-UPDRS will also be retained for the full retention period of 
at least 15 years.
For countries where ethics committees or the Ministry of Health will not approve 
audio/video recording of participant interviews, review of the scale worksheets, 
submitted as part of the assessment source information, will be performed to verify 
accuracy of scoring and adherence to study conventions.
8.
ETHICAL CONSIDERATIONS
8.1
COMPLIANCE WITH LAWS AND REGULATIONS
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the laws and 
regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual. The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management: Definitions and Standards for 
Expedited Reporting). Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) application will comply with U.S. FDA regulations and 
applicable local, state, and federal laws. Studies conducted in the EU/EEA will comply 
with the EU Clinical Trial Directive (2001/20/EC).
8.2
INFORMED CONSENT
The Sponsor’s sample Informed Consent Form will be provided to each site. If applicable, 
it will be provided in a certified translation of the local language. The Sponsor or its 
designee must review and approve any proposed deviations from the Sponsor's sample 
Informed Consent Forms or any alternate consent forms proposed by the site 
(collectively, the “Consent Forms”) before IRB/EC submission. The final 
IRB/EC‑approved Consent Forms must be provided to the Sponsor for Health Authority 
submission purposes according to local requirements.
The Consent Forms must be signed and dated by the participant or the participant’s 
legally authorized representative before his or her participation in the study. The case 
history or clinical records for each participant shall document the informed consent 
process and that written informed consent was obtained prior to participation in the study.
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the 
participant to take part. The final revised IRB/EC-approved Consent Forms must be 
provided to the Sponsor for Health Authority submission purposes.

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Participants must be re-consented to the most current version of the Consent Forms (or 
to a significant new information/findings addendum in accordance with applicable laws 
and IRB/EC policy) during their participation in the study. For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study.
A copy of each signed Consent Form must be provided to the participant or the 
participant’s legally authorized representative. All signed and dated Consent Forms must 
remain in each participant’s study file or in the site file and must be available for 
verification by study monitors at any time.
For sites in the United States, each Consent Form may also include participant 
authorization to allow use and disclosure of personal health information in compliance 
with the U.S. Health Insurance Portability and Accountability Act of 1996 (HIPAA). If the 
site utilizes a separate Authorization Form for participant authorization for use and 
disclosure of personal health information under the HIPAA regulations, the review, 
approval, and other processes outlined above apply except that IRB review and approval 
may not be required per study site policies.
8.3
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE
This protocol, the Informed Consent Forms, any information to be given to the participant, 
and relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated. In 
addition, any participant recruitment materials must be approved by the IRB/EC.
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC. Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.5).
In addition to the requirements for reporting all adverse events to the Sponsor, 
Investigators must comply with requirements for reporting serious adverse events to the 
local Health Authority and IRB/EC. Investigators may receive written IND safety reports 
or other safety‑related communications from the Sponsor. Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with Health 
Authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site’s study file.
8.4
CONFIDENTIALITY
The Sponsor maintains confidentiality standards by coding each participant enrolled in 
the study through assignment of a unique participant identification number. This means 
that participant names are not included in data sets that are transmitted to any Sponsor 
location.

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Participant medical information obtained by this study is confidential and may only be 
disclosed to third parties as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
participant, unless permitted or required by law.
Medical information may be given to a participant’s personal physician or other 
appropriate medical personnel responsible for the participant’s welfare, for treatment 
purposes.
Data generated by this study must be available for inspection upon request by 
representatives of the U.S. FDA and other national and local Health Authorities, monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate.
8.5
FINANCIAL DISCLOSURE
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate Health Authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for one year after completion of the study (i.e., Last Participant 
Last Follow-Up Visit).
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION
9.1
STUDY DOCUMENTATION
The Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including but not limited to the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval. In addition, at the end of the study, the Investigator will receive 
the participant data, which includes an audit trail containing a complete record of all 
changes to data.
Roche shall also submit a Development Safety Update Report (DSUR) once a year to 
the IEC and Competent Authorities according to local regulatory requirements and 
timelines of each country participating in the study.
It is the understanding of the Sponsor that this protocol (and any modifications) as well 
as appropriate consent procedures and advertisements, will be reviewed and approved 
by an Institutional Review Board (IRB). This board must operate in accordance with the 
current Federal Regulations. The Sponsor will be sent a letter or certificate of approval 
prior to initiation of the study, and also whenever subsequent amendments/modifications 
are made to the protocol. Roche shall also submit an IND Annual Report to FDA 
according to local regulatory requirements and timelines.

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9.2
SITE INSPECTIONS
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, participants’ medical records, and eCRFs. The Investigator will 
permit national and local Health Authorities, monitors, representatives, and collaborators, 
and the IRBs/ECs to inspect facilities and records relevant to this study.
9.3
ADMINISTRATIVE STRUCTURE
The Sponsor of the trial is F. Hoffmann – La Roche Ltd. The Sponsor is responsible for 
the study management, data management, statistical analysis and medical writing for 
the clinical study report.
A Contract Research Organization (CRO) will be responsible for the feasibility activities, 
countries and site management as well of other operational activities as appropriate. 
Medical Monitoring activities may be split between the Sponsor and the CRO. 
An IxRS will be used to register the screening/screening failures, enrolment, drug 
allocation, withdrawal, early discontinuation, study completion of the participants.
A central laboratory will be used to provide sample kits to all sites and collect samples 
for the assessments listed in Section 4.6.1.5.
Specific external laboratories will be used to analyze the CSF samples, skin biopsies, 
PK samples and optional blood samples.
A central ECG company will provide all sites with ECG equipment and will collect ECGs 
electronically or on paper where required. The ECGs will be reviewed for safety 
purposes by this company.
Central imaging companies will collect the MRI and DaT-SPECT scans and analyze 
them as per the study defined requirements (see Section 4.6.1.9).
An external company and external consultants will provide training to all site raters on 
the various scales and will provide all sites with the relevant record forms, instruction 
manuals and kits as appropriate.
All other training, data acquisition and handling will be conducted by the Sponsor.
9.4
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
prior to submission. This allows the Sponsor to protect proprietary information and to 
provide comments based on information from other studies that may not yet be available 
to the Investigator.

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The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data. In this case, a coordinating investigator will be designated by mutual agreement.
Any formal publication of the study in which contribution of Sponsor personnel exceeded 
that of conventional monitoring will be considered as a joint publication by the 
Investigator and the appropriate Sponsor personnel.
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise.
9.5
PROTOCOL AMENDMENTS
Any substantial protocol amendments will be prepared by the Sponsor. Substantial 
protocol amendments will be submitted to the IRB/EC and to regulatory authorities in 
accordance with local regulatory requirements.
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to participants or any non-substantial changes, as 
defined by regulatory requirements.

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10.
REFERENCES
Alsop DC, Detre JA, Golay X, et al. Recommended implementation of arterial spin-
labeled perfusion MRI for clinical applications: A consensus of the ISMRM 
perfusion study group and the European consortium for ASL in dementia. MRI in 
Medicine. 2015;73:102–116.
Beach TG, Adler CH, Lue L, et al. Arizona Parkinson's Disease Consortium. Unified 
staging system for Lewy body disorders: correlation with nigrostriatal degeneration, 
cognitive impairment and motor dysfunction. Acta Neuropathol. 2009;117:613-634.
Beal S, Sheiner L (Eds.). NONMEM Users Guides, NONMEM Project Group, University 
of California at San Francisco, San Francisco. 1998.
Bhidayasiri R, Reichmann H. Different diagnostic criteria for Parkinson disease: What 
are the pitfalls? J Neural Transm. 2013;120:619–625.
Braak H, Del Tredici K, Rüb U, et al. Staging of brain pathology related to sporadic 
Parkinson's disease. Neurobiol Aging. 2003;24:197-211.
Buatois S, Retout S, Gieschke R, et al. Using Item response theory to yield information 
from the MDS-UPDRS items in Parkinson’s disease clinical trials. Page Meeting 
2015 Website: http://www.page-meeting.org/?abstract=3417.
Buatois S, Retout S, Frey N, et al. Utilizing the items from the MDS-UPDRS score to 
increase drug effect detection power in de novo idiopathic Parkinson's disease 
patients. Page Meeting 2016 Website: http://www.page-
meeting.org/default.asp?abstract=5865.
Burke RE, O'Malley K. Axon degeneration in Parkinson's disease. Exp Neurol. 
2013;246:72-83.
de la Fuente-Fernández R, Schulzer M, Kuramoto L, et al. Age-specific progression of 
nigrostriatal dysfunction in Parkinson's disease. Ann Neurol. 2011 May;69(5):803-
810.
de Lau LM, Schipper CM, Hofman A, et al. Prognosis of Parkinson disease: risk of 
dementia and mortality: the Rotterdam Study. Arch Neurol. 2005;62:1265-1269.
Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson's 
disease: refining the diagnostic criteria. Lancet Neurol. 2009;8:1150-1157.
Donadio V, Incensi A, Leta V, et al. Skin nerve -synuclein deposits: a biomarker for 
idiopathic Parkinson disease. Neurology. 2014;82:1362-1369.
Du G, Lewis M M, Sica C, et al. Distinct progression pattern of susceptibility MRI in 
the substantia nigra of Parkinson’s patients. Mov Dis. 2018;33: 1423–1431. 
Dukart J, Sambataro F, Bertolino A. Distinct Role of Striatal Functional Connectivity 
and Dopaminergic Loss in Parkinson’s Symptoms. Frontiers in Aging 
Neuroscience 2017;9:151.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
125/Protocol BP39529, Version 6
Frank L, Kleinman L, Farup C, et al. Psychometric validation of a constipation symptom 
assessment questionnaire. Scandinavian J Gastroenterol. 1999;348:70–77.
Gaurav R, Pyatigorskaya N, Ewenczyk C, et al. Longitudinal changes in Neuromelanin 
MRI Signal in Parkinson's Disease. Mov Disord. 2018;33: 641-642.
Gazyvaro Summary of Product Characteristics. 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/002799/WC500171594.pdf. Accessed 13 February 
2017.
Gelb DJ, Oliver E, Gilman S Diagnostic Criteria for Parkinson Disease. Arch Neurol. 
1999;56:33-39.
Gibb WRG, Lees AJ. The relevance of Lewy body to the pathogenesis of idiopathic 
Parkinson’s disease. J Neurol Neurosurg Psych. 1988;51:745-752.
Guy W. ECDEU assessment manual for psychopharmacology. U.S. Dept. of Health, 
Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental 
Health Administration, National Institute of Mental Health, Psychopharmacology 
Research Branch, Division of Extramural Research Programs in Rockville, Md, 
1976.
Hilli J, Korhonen T, Laine K. Lack of clinically significant interactions between 
concomitantly administered rasagiline and escitalopram. Prog 
Neuropsychopharmacol Biol Psychiatry. 2009;33:1526–32.
Hoehn M, Yahr M. Parkinsonism: Onset, progression and mortality. Neurology. 
1967;17(5):427–442.
Huang C, Tang C, Feigin A, et al. Changes in network activity with the progression of 
Parkinson's disease. Brain. 2007;130:1834-1846.
Ibáñez P, Bonnet AM, Débarges B, et al. Causal relation between alpha-synuclein gene 
duplication and familial Parkinson's disease. Lancet. 2004;364(9440):1169-1171.
Jankovic J, Goodman I, Safirstein B et al. Safety and tolerability of multiple ascending 
doses of PRX002/RG7935, an anti--synuclein monoclonal antibody, in patients 
with Parkinson disease. A randomized Clinical trial. JAMA Neurol. 2018;
doi:10.1001/jamaneurol.2018.1487.
Kassavetis P, Saifee TA, Roussos G, et al. Developing a Tool for Remote Digital 
Assessment of Parkinson's Disease. Mov Dis Clin Pract. 2016;3:59–64.
Kay DM, Factor SA, Samii A, et al. Genetic association between alpha-synuclein and 
idiopathic Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet. 
2008;147B(7):1222-1230. 
Kostikis N, Hristu-Varsakelis D, Arnaoutoglou M, et al. Smartphone-based evaluation of 
parkinsonian hand tremor: quantitative measurements vs clinical assessment 
scores. Conf Proc IEEE Eng Med Biol Soc. 2014:906-909.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
126/Protocol BP39529, Version 6
Kowal SL, Dall TM, Chakrabarti R, et al. The current and projected economic burden of 
Parkinson's disease in the United States. Mov Disord. 2013;28:311-318.
Lieberman P, Nicklas R, Randolph C et al. Anaphylaxis-a practice parameter 
update. Annals Allergy Asthma Immunol. 2015;115(5):341–384.
Lipsmeier F, Taylor KI, Kilchenmann T, et al. Evaluation of smartphone-based testing to 
generate exploratory outcome measures in a Phase I Parkinson's disease clinical 
trial. Mov Disord. 2018; doi: 10.1002/mds.27376. 
Little MA, McSharry PE, Hunter EJ, et al. Suitability of dysphonia measurements for 
telemonitoring of Parkinson’s disease, IEEE Transactions on Biomedical 
Engineering 2009;56(4):1015-1022.
Maetzler W, Domingos J, Srulijes K. Quantitative wearable sensors for objective 
assessment of Parkinson's disease. Mov Disord. 2013;28:1628–1637.
Malek N, Swallow D, Grosset KA, et al. Alpha-synuclein in peripheral tissues and body 
fluids as a biomarker for Parkinson's disease - a systematic review. Acta Neurol 
Scand. 2014;130:59-72.
Maetzler P, Zhang S, Li C-SR, et al. Resting-state functional connectivity of the striatum 
in early-stage Parkinson's disease: Cognitive decline and motor symptomatology. 
Human Brain Mapping. 2016;37:648–662.
Manza P, Zhang S, Li C-SR, et al. Resting-state functional connectivity of the striatum in 
early-stage Parkinson's disease: Cognitive decline and motor symptomatology. 
Human Brain Mapping. 2016;37:648–662.
Marek K, Jennings D, Lasch S, et al. The Parkinson Progression Marker Initiative (PPMI). 
Prog Neurobiol. 2011;95(4):629-635. 
Matsuura K, Maeda M, Tabei K et al. A longitudinal study of neuromelanin-sensitive 
magnetic resonance imaging in Parkinson’s disease. Neuroscience Letters. 
2016;633, 112–117.
Montgomery EB, Panisset M. Retrospective analysis of the incidence of serotonin 
toxicity in patients taking rasagiline and antidepressants in clinical trials. Mov 
Disord. 2009;24:359 (abstract).
Mutsaerts HJ, van Osch MJ, Zelaya FO, et al. Multi-vendor reliability of arterial spin 
labeling perfusion MRI using a near-identical sequence: implications for multi-
center studies. Neuroimage. 2015;113:143-152.
Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal evolution of compensatory 
changes in striatal dopamine processing in Parkinson's disease. Brain. 
2011;134:3290-3298.
Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, 
MoCA: A Brief Screening Tool For Mild Cognitive Impairment. J Americ Geriatrics 
Soc. 2005;53:695–699.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
127/Protocol BP39529, Version 6
National Institute of Neurological Disorders and Stroke. 
http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.
htm. Accessed 30 January 2017.
NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. 
Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, 
randomised trial. Lancet Neurol. 2015;14(8):795-803. Erratum in: Lancet Neurol. 
2015; 14(10):979.
Olde Dubbelink KT, Schoonheim MM, Deijen JB, et al. Functional connectivity and 
cognitive decline over 3 years in Parkinson disease. Neurology. 2014;83:2046-
2053.
Ossig C, Antonini A, Buhmann C, et al. Wearable sensor-based objective assessment of 
motor symptoms in Parkinson’s disease. JNeural Transm. 2016;123:57–64.
Panisset M, Chen JJ, Rhyee SH, et al. Serotonin toxicity association with concomitant 
antidepressants and rasagiline treatment: retrospective study (STACCATO). 
Pharmacotherapy. 2014;34:1250-1258.
Parkinson’s Disease Foundation. http://www.pdf.org/en/parkinson_statistics. Accessed 
30 January 2017.
Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the 
TEMPO Study. Arch Neurol. 2002;59(12):1937-1943.
Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson 
disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044-53.
Parkinson Study Group PRECEPT Investigators. Mixed lineage kinase inhibitor 
CEP-1347 fails to delay disability in early Parkinson disease. Neurology. 
2007;69(15):1480-1490. 
Patel S, Chen B, Mancinelli C, et al. Longitudinal Monitoring of Patients with Parkinson’s 
Disease via Wearable Sensor Technology in the Home Setting. Conf Proc IEEE 
Eng Med Biol Soc. 2011:1552-1555.
Peto V, Jenkinson C, Fitzpatrick R. The development and validation of a short measure 
of functioning and well being for individuals with Parkinson's disease. Quality of 
Life Res. 1995;4:241–248.
Posner K, Brown GK, Stanley B, et al., The Columbia-Suicide Severity Rating Scale: 
Initial Validity and Internal Consistency Findings From Three Multisite Studies With 
Adolescents and Adults. Am J Psychiatry. 2011;168:1266-1277.
Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's 
disease. Mov Disord. 2015 Oct;30(12):1591-601. 
Prodoehl J, Burciu RG, Vaillancourt, DE. Resting state functional magnetic resonance 
imaging in Parkinson’s Disease. Curr Neurol Neurosci Rep. 2014;14:448-455.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
128/Protocol BP39529, Version 6
Rascol O, Fitzer-Attas CJ, Hauser R, et al. A double-blind, delayed-start trial of 
rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc 
analyses of the need for additional therapies, changes in UPDRS scores, and non-
motor outcomes. Lancet Neurol. 2011;10(5):415-423. 
Reijnders, J. A Systematic Review of Prevalence Studies of Depression in Parkinson’s 
Disease. Mov.Disord. 2008;23:183–189.
RO7046015 Investigator’s Brochure, Version 6, February 2020.
Schenk DB, Koller M, Ness DK, et al. First-in-Human Assessment of PRX002, an Anti–
a-Synuclein Monoclonal Antibody, in Healthy Volunteers. Mov Disord. 2016 Nov 25. 
doi: 10.1002/mds.26878. [Epub ahead of print]
Schwab RS, England AC. Projection technique for evaluating surgery in Parkinson’s 
disease. In: Gillingham FJ, Donaldson IML, eds. Third Symposium on Parkinson’s 
disease. Edinburgh: E & S Livingstone. 1969;152–157.
Schwarz J, Storch A, Koch W, et al. Loss of Dopamine Transporter Binding in 
Parkinson’s Disease Follows a Single Exponential Rather Than Linear Decline. J 
Nucl Med. 2004;45:1694-1697.
Schwid SR, Parkinson Study Group. Safety of rasagiline in combination with serotonin 
reuptake inhibitors. Ann Neurol. 2005;58(suppl 9):56.
Simuni T, Caspell-Garcia C, Coffey C, et al. One year longitudinal change in the MDS‐
UPDRS scores in de novo Parkinson's disease patients: Results from the PPMI 
study [abstract]. Mov Disord. 2015;30 Suppl 1 :319.
Singleton AB, Farrer M, Johnson J, et al. Alpha-Synuclein locus triplication causes 
Parkinson's disease. Science. 2003;302(5646):841.
Smith KM, Eyal E, Weintraub D, et al. Combined rasagiline and antidepressant use in 
Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and 
tolerability. JAMA Neurol. 2015;72:88-95.
Snaith RP, Zigmond AS. Hospital Anxiety and Depression Scale (HADS). In: Rush AJ, 
editors. Handbook of psychiatric measures. Washington D.C.: Am Psychiatric Ass. 
2000;547–548.
Spillantini MG, Schmidt ML, Lee VM, et al. Alphasynuclein in Lewy bodies. Nature. 
1997;388:839-840.
Sprenger F, Poewe W. Management of Motor and Non-Motor Symptoms in Parkinson’s 
Disease. CNS Drugs 2013;27:259–272.
Taylor KI, Sambataro F, Boess F, et al. Progressive Decline in Gray and White Matter 
Integrity in de novo Parkinson’s Disease: An Analysis of Longitudinal Parkinson 
Progression Markers Initiative Diffusion Tensor Imaging Data. Frontiers in 
Aging Neuroscience 2018;10:318.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
129/Protocol BP39529, Version 6
Teune LK, Renken RJ, de Jong BM, et al. Parkinson's disease-related perfusion and 
glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET 
imaging. Neuroimage Clin. 2014;5:240-244.
Trenkwalder C, Kohnen R, Högl B. Parkinson’s Disease Sleep Scale - Validation of the 
Revised Version PDSS-2. Mov Disord. 2011;26:644-652.
Tsanas A, Little MA, McSharry PE, et al. Accurate telemonitoring of Parkinson’s disease 
progression by noninvasive speech tests. 2010. IEEE Trans Biomed Eng. 
2010;57:884–893.
Ueckert S, Plan EL, Ito K, et al. AC. Improved Utilization of ADAS-Cog Assessment Data 
Through Item Response Theory Based Pharmacometric Modeling. Pharm Res. 
2014;31(8):2152-2165.
Ulla M, Bonny J M, Ouchchane L, et al. Is R2* a New MRI Biomarker for the 
Progression of Parkinson’s Disease? A Longitudinal Follow-Up. PLoS ONE. 
2013;8(3), e57904.
Visser M, Marinus J, Stiggelbout AM, et al. Assessment of autonomic dysfunction in 
Parkinson's disease: the SCOPA-AUT. Mov Disord. 2004;19;1306-1312.
Wan W, Jin L, Wang Z, et al. Iron deposition leads to neuronal α-synuclein pathology 
by inducing autophagy dysfunction. Frontiers in Neurology. 2017;8:2–11. 
Wang N, Gibbons CH, Lafo J, et al. -Synuclein in cutaneous autonomic nerves. 
Neurology. 2013;81:1604-1610.
Wang J, Zhuang Q, Zhu L, et al. Meta-analysis of brain iron levels of Parkinson’s 
disease patients determined by postmortem and MRI measurements. Scientific 
Reports. 2016; 6:1–13. 
Wang X, Zhang Y, Zhu C, et al. The diagnostic value of SNpc using NM-MRI in 
Parkinson’s disease: meta-analysis. Neurological Sciences. 2019;40:2479–2489.
Weintraub D, Burn DJ. Parkinson’s Disease: The Quintessential Neuropsychiatric 
Disorder. Mov Disord. 2011;26:1022-1031.
Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) 
Investigators., Kieburtz K, Tilley BC, Elm JJ, et al. Effect of creatine monohydrate 
on clinical progression in patients with Parkinson disease: a randomized clinical 
trial. JAMA. 2015;313(6):584-93. 
Wu P, Wang J, Peng S, et al. Metabolic brain network in the Chinese patients with 
Parkinson's disease based on 18F-FDG PET imaging. Parkinsonism & Related 
Disorders. 2013;19:622–627.
Zhang Y, Wu I-W, Tosun D, et al. Progression of regional microstructural degeneration 
in parkinson's disease: a multicenter diffusion tensor imaging study. PLOS one. 
2016;11: e0165540.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
130/Protocol BP39529, Version 6
Appendix 1
Schedule of Assessments (Part 1)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
131/Protocol BP39529, Version 6
Appendix 1
Schedule of Assessments (Part 1) (cont.)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
132/Protocol BP39529, Version 6
Appendix 1
Schedule of Assessments (Part 1) (cont.)
1
If participants discontinue or withdraw from the study treatment prematurely, they should complete all of the Early Termination assessments and 
attend the Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
2
Screening serum pregnancy test for women who are not post-menopausal or surgically sterile. Urine pregnancy test for female participants (based on 
participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
3
Screening brain MRI should only be performed after all other inclusion and exclusion have been reviewed and none exclude the participant from the 
trial, except DaT-SPECT which should be the final assessment. Screening MRI to include Structural, resting state functional MRI (rs-fMRI), 
Diffusion Tensor Imaging (DTI), Arterial Spin Labelling (ASL). Please note that rs-fMRI, DTI and ASL sequences will only be acquired if the investigative 
sites have the required scanner software/sequences capabilities.
4
Day 1 / Week 4 / 20 / 36 / 52: serum RO7046015 (PK Sampling) and serum biomarker samples will be collected just prior to dosing and at the end of 
the infusion. At Days 7 / 14 / early termination and FUP: anytime (all time points of collection to be recorded in CRF). 
5
ECG (12-lead) will be obtained at pre-dose on Day 1 and again at the end of study drug infusion. For all the designated dosing visits the ECGs should 
be obtained at pre-dose only. For the Screening/early termination/FUP, the ECGs should be obtained early in the day to approximate the timing of the 
pre-dose ECGs during the study. All ECGs (12-lead) will be performed in triplicate, 1-2 minutes apart within 5 minutes. 
6
Vital signs (including semi-supine blood pressure, respiratory rate, pulse rate and temperature) have to be monitored pre-infusion, every 15 minutes 
until the end of infusion, and thereafter, every 30 minutes until the infusion line is removed.  In order to assess for orthostatic hypotension, BP and 
pulse rate will be evaluated after 2 minutes of standing still (after the semi-supine measurement) at screening and at pre-dose and 2 hours after 
completion of the first three infusions then 1 hour after end of infusion on subsequent dosing days. Note: any abnormal value in Vital Signs needs to 
be repeated for confirmation or intervention if needed. 
7
Height and weight will be recorded at the screening visit only. Only weight will be measured at baseline, Weeks 52 and FUP.
8
On dosing days, serum anti-RO7046015 antibody samples will be collected prior to dosing as done for PK samples.
9
For consented participants only. Baseline lumbar puncture (LP) should be performed prior to Day -4 to allow recovery before first dosing. Then the 
ideal collection time is between 48-72 hours after the Week 52 infusions and early termination.  LP should be performed in the morning (between 
8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters. Please refer to the protocol for handling of AEs related to LP and 
instructions on concomitant medication. An aliquot of the CSF samples will be sent for local laboratory analysis (erythrocyte and leukocyte cell counts, 
protein, and glucose) while the remainder of the sample will be sent for central biomarker assessment. Any remaining CSF aliquots will be stored for 
the Research Biosample Repository for patients participating in RBR. 

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133/Protocol BP39529, Version 6
Appendix 1
Schedule of Assessments (Part 1) (cont.)
10
MRI and DaT-SPECT scans should not be performed if already collected within 3 months of early termination. If a DaT-SPECT scan is required for early 
termination visit, TSH and T4 assessment must be performed prior to the scan.
11
Skin biopsy must be collected pre-dose if the sample is collected at visits with study drug administration.
12
At screening, Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on 
dopaminergic treatment (levodopa or dopamine agonist). For all participants that have started dopaminergic treatment, the MDS-UPDRS I-
III, including Part IV and Digital Biomarker In-Clinic assessments will be assessed approximately 12 hours (e.g., overnight) after last dose of 
dopaminergic treatment. Only the MDS-UPDRS Part III and Digital Biomarker In-Clinic Assessments will then be repeated 1 hour after receiving 
dopaminergic treatment in the clinic.
13
The first Digital Biomarker In-Clinic Assessments should be done at least 7 days prior to Baseline. In Clinic Digital Biomarker Assessments include the 
Full Active Test, Short Berg Balance Test and Timed Up and Go.
14
Telephone interview on Day 2 and, for those subjects not participating in PK sampling, on Days 7 and 14 to assess for any clinically significant 
symptoms and/or new medication.
15
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at 
visit.
16
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to 
the visit clinic or within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case 
participant takes dopaminergic treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of 
evaluation).
17
Fasting glucose will be analyzed at screening.
18
During screening, the Digital Biomarker Remote Monitoring should be started at least 7 days prior to Baseline. The PROs (patient reported outcome) 
are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed remotely since the 
scheduled days will often fall between clinic visit days.
19
Premedication is given 30-60 min prior to the first 3 infusions. Desloratadine 5 mg PO or other alternatives can be given in study centers where 
loratadine is not available.
20
Study drug should be given as IV infusion over 2 hours for the first three doses and if well tolerated can be reduced to 1 hour in subsequent doses.
21
Days 7 and 14 on-site visits will only be performed in the first 90 participants enrolled at sites in the USA. A telephone interview on Days 7 and 14 to 
assess clinically significant symptoms and/or new medications will be done for all other participants.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
134/Protocol BP39529, Version 6
Appendix 2
Schedule of Assessments (Part 2)
Week
Week 56
Week 60
Week 64
Week 68
Week 72
Week 76
Week 80
Week 84
Week 88
Week 92
Week 96
Week 100
Week 104
Day
Day 392
Day 420
Day 448
Day 476
Day 504
Day 532
Day 560
Day 588
Day 616
Day 644
Day 672
Day 700
Day 728
Visit Window
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  7 days
Dose Number
15
16
17
18
19
20
21
22
23
24
25
26
27
Assessments
Eligibilty for Extension15
x
Modified Hoehn & Yahr
x
x
x
x
x
x
x
x
x
x
MDS UPDRS (Parts I, II, III, IV)10
x
x
x
x
x
x
x
x
x
x
Vital Signs5
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic BP5
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical Examination (Full)
x
x
x
x
x6
Physical Examination (Abbreviated)14
x
x
x
x
x
x
x
x
x
x
x
Neurological Examination
x
x
x
x
x
x
CGII/PGIC
x
x
x
x
x
x
MoCA
x
x
x
x
x
x
C SSRS (Since Last Visit)
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
PDQ 39
x
x
x
x
x
SCOPA AUT
x
x
x
x
x
x
Schwab & England  ADL
x
x
x
x
x
RBDSQ Multi item
PDSS 2
x
x
x
x
x
x
Digital Biomarker Remote Monitoring (incl. diary 
questions, HADS, PAC SYM, EQ 5D 5L) 17
Digital Biomarker In Clinic Assessments 12
x
x
x
x
x
x
x
x
x
x
Triplicate ECG 12 lead4
x
x
x
x
x
x
x
DaT SPECT16
x
x9
MRI (safety & efficacy)16
x
x9
Phone Call13
Week 57
Day 393
Prior to Start of 
Dopaminergic/Sy
mptomatic PD 
Treatment (if 
occuring during 
Part 2)
Early 
Termination1 (if 
occuring during 
Part 2)
12 Week Treatment Free 
FUP 1 (at end of study or if 
treatment terminated in 
Part 2)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
135/Protocol BP39529, Version 6
Appendix 2
Schedule of Assessments (Part 2) (cont.)
Week
Week 56
Week 60
Week 64
Week 68
Week 72
Week 76
Week 80
Week 84
Week 88
Week 92
Week 96
Week 100
Week 104
Day
Day 392
Day 420
Day 448
Day 476
Day 504
Day 532
Day 560
Day 588
Day 616
Day 644
Day 672
Day 700
Day 728
Visit Window
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  4 days
+/  7 days
Dose Number
15
16
17
18
19
20
21
22
23
24
25
26
27
Assessments
Hematology
x
x
x
x
x
x
x
x
x
x
x
Blood Chemistry and Lipids
x
x
x
x
x
x
x
x
Coagulation
x
x
x
x
x
x
x
x
TSH and T4
x
x9
Urinalysis
x
x
x
x
x
x
x
x
Pregnancy Test2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum RO7046015 (PK sampling)3
x
x
x
x
x
x
x
Serum Biomarker3
x
x
x
x
x
x
x
Serum Anti RO7046015 Antibody7
x
x
x
x
x
x
x
Optional CSF via Lumbar Puncture (matching 
serum sample)8
x
x
x
PreMedication  Loratadine 10mg PO, 
Acetaminophen 650 mg PO 18
x
x
x
Administration of Study Medication
x 19
x 19
x 19
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x11
x11
x
RBR  Optional Whole Blood RNA
x
x
x
x
RBR  Optional Whole Blood Plasma
x
x
x
x
Adverse Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and Concomitant Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Phone Call13
Week 57
Day 393
x13
x13
Prior to Start of 
Dopaminergic/Sy
mptomatic PD 
Treatment (if 
occuring during 
Part 2)
Early 
Termination1 (if 
occuring during 
Part 2)
12 Week Treatment Free 
FUP 1 (at end of study or if 
treatment terminated in 
Part 2)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
136/Protocol BP39529, Version 6
Appendix 2
Schedule of Assessments (Part 2) (cont.)
1
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Early Termination assessments and attend the 
Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
2
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
3
Week 56 / 68 / 80 / 104: serum RO7046015 (PK sampling) and serum biomarkers samples will be collected just prior to dosing and at the end of the infusion. At 
early termination and FUP: anytime (all time points of collection to be recorded in CRF). 
4
On Week 56 ECG will be obtained pre-dose and at end of study drug infusion. For all the designated dosing visits the ECGs should be obtained at pre-dose only. 
For the early termination/FUP the ECG timing should be early in the visit to approximate the pre-dose measurements. All ECGs (12-lead) will be performed in 
triplicate, 1-2 minutes apart within 5 minutes.
5
Vital signs (including semi-supine blood pressure, respiratory rate, pulse rate and temperature) have to be monitored pre-infusion, every 15 minutes until the 
end of infusion, and thereafter, every 30 minutes until the infusion line is removed. In order to assess for orthostatic hypotension, BP and pulse rate will be 
evaluated after 2 minutes of standing still (after the semi-supine measurement) at pre-dose and 2 hours after completion of the first three infusions then 1 hour 
after end of infusion on subsequent dosing days.  Note:  any abnormal value in Vital Signs needs to be repeated for confirmation or intervention if needed. 
6
Height will not be measured at FUP. 
7
On dosing days, serum anti-RO7046015 antibody samples will be collected prior to dosing as done for PK samples.
8
For consented participants only. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after the Week 104 infusion and early 
termination. LP should be performed in the morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters. An aliquot of 
the CSF samples will be sent for local laboratory analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be 
sent for central biomarker assessment. Any remaining CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
9
MRI and DaT-SPECT scans should not be performed if already collected within 3 months of early termination. If a DaT-SPECT scan is required for early 
termination visit, TSH and T4 assessment must be performed prior to the scan.
10
MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment (levodopa or dopamine agonist). For all participants that have started 
dopaminergic treatment, the MDS-UPDRS Parts I- III, including Part IV and Digital Biomarker In-Clinic assessments, will be assessed approximately 12 hours (e.g., 
overnight) after last dose of dopaminergic treatment.  Only the MDS-UPDRS Part III and Digital Biomarker In-Clinic assessments will then be repeated 1 hour 
after receiving dopaminergic treatment in the clinic.
11
Skin biopsy must be collected pre-dose if the sample is collected at visits with study drug administration.
12
In Clinic Digital Biomarker Assessments include the Full Active Test, Short Berg Balance Test, and Timed Up and Go.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
137/Protocol BP39529, Version 6
Appendix 2
Schedule of Assessments (Part 2) (cont.)
13
Telephone interview to assess for any clinically significant symptoms and/or new medication.
14
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit.
15
The participants must meet the following criteria to enter the Part II: Dat-SPECT and MRI scans completed at screening and Week 52 and at least 10 doses of 
study treatment.
16
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic 
visit or within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes 
dopaminergic treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
17
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be 
completed remotely since the scheduled days will often fall between clinic visit days.
18
Premedication is given 30-60 min prior to the first 3 infusions.
19
Study drug should be given as IV infusion over 2 hours for the first three doses and if well tolerated can be reduced to 1 hour in subsequent doses.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
138/Protocol BP39529, Version 6
Appendix 3
Schedule of Assessments (Part 3)
Part 3 is a 5-year extension. Please see separate SoA for each year as follows:
Schedule of Assessments Part 3 - Year 1
Schedule of Assessments Part 3 - Year 2
Schedule of Assessments Part 3 - Year 3
Schedule of Assessments Part 3 - Year 4
Schedule of Assessments Part 3 - Year 5

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
139/Protocol BP39529, Version 6
Schedule of Assessments Part 3 - Year 1
Treatment 
Week
Part 3 Week 1
Part 3 Week 4
Part 3 Week 8
Part 3 Week 12 Part 3 Week 16 Part 3 Week 20 Part 3 Week 24 Part 3 Week 28 Part 3 Week 32 Part 3 Week 36 Part 3 Week 40 Part 3 Week 44 Part 3 Week 48 Part 3 Week 52
Unscheduled
Treatment Day
Day 1
Day 28
Day 56
Day 84
Day 112
Day 140
Day 168
Day 196
Day 224
Day 252
Day 280
Day 308
Day 336
Day 364
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Assessments
Eligibilty for 
Extension1
x
Modified 
Hoehn & Yahr
x
x
x
x
x
x
x
x
x
MDS-UPDRS 
(Parts I, II, III, 
IV)3
x
x
x
x
x
x
x
x
x
Vital Signs4
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic 
BP4
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical 
Examination 
(Full)5
x2
x
x
x
x
x
Physical 
Examination 
(Abbreviated)6
x
x
Neurological 
Examination
x2
x
x
x
x
x
x
CGII/PGIC
x2
x
x
x
x
x
x
MoCA
x2
x
x
x
x
x
x
C-SSRS (Since 
Last Visit)
x2
x
x
x
x
x
x
PDQ-39
x2
x
x
x
x
x
x
SCOPA-AUT
x2
x
x
x
x
x
x
Schwab & 
England - ADL
x2
x
x
x
x
x
x
PDSS-2
x2
x
x
x
x
x
x
Digital 
Biomarker 
Remote 
Monitoring 
(incl. diary 
questions, 
HADS, PAC-
SYM, EQ-5D-
5L) 7
x20
x20
x20
x20
x20
x
x21
x21
Digital 
Biomarker In-
Clinic 
Assessments 8
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination18 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 18 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
140/Protocol BP39529, Version 6
Part 3 - Year 1 (cont.)
Treatment 
Week
Part 3 Week 1
Part 3 Week 4
Part 3 Week 8
Part 3 Week 12 Part 3 Week 16 Part 3 Week 20 Part 3 Week 24 Part 3 Week 28 Part 3 Week 32 Part 3 Week 36 Part 3 Week 40 Part 3 Week 44 Part 3 Week 48 Part 3 Week 52
Unscheduled
Treatment Day
Day 1
Day 28
Day 56
Day 84
Day 112
Day 140
Day 168
Day 196
Day 224
Day 252
Day 280
Day 308
Day 336
Day 364
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Assessments
Triplicate ECG-
12 lead9
x
x
x
x
x
Pre dose 12-
Lead ECG
x
x
x
DaT-SPECT10
x19
MRI (safety & 
efficacy)10
x2
x
x19
Hematology
x2
x
x
x
x
x
x
x
x
Blood 
Chemistry and 
Lipids
x2
x
x
x
x
x
x
Coagulation
x2
x
x
x
x
x
x
TSH and T4
x
x
x19
Urinalysis
x2
x
x
x
x
x
x
Pregnancy 
Test11
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum 
RO7046015 
(PK 
sampling)12
x
x
x
x
x
x
Serum and 
plasma 
Biomarker12
x
x
x
x
x
x
x
Serum Anti-
RO7046015 
Antibody13
x
x
x
x
x
x
Optional CSF 
via Lumbar 
Puncture 
(matching 
serum and 
plasma 
sample)14
x
x19
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination18 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 18 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
141/Protocol BP39529, Version 6
Part 3 - Year 1 (cont.)
Treatment 
Week
Part 3 Week 1
Part 3 Week 4
Part 3 Week 8
Part 3 Week 12 Part 3 Week 16 Part 3 Week 20 Part 3 Week 24 Part 3 Week 28 Part 3 Week 32 Part 3 Week 36 Part 3 Week 40 Part 3 Week 44 Part 3 Week 48 Part 3 Week 52
Unscheduled
Treatment Day
Day 1
Day 28
Day 56
Day 84
Day 112
Day 140
Day 168
Day 196
Day 224
Day 252
Day 280
Day 308
Day 336
Day 364
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Assessments
PreMedication 
Loratadine 
10mg PO, 
Acetaminophe
n 650 mg PO 
15
x
Administration 
of Study 
Medication
x 16
x
x
x
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x17
x
RBR - Optional 
Whole Blood 
RNA
x
x
x
x
RBR - Optional 
Whole Blood 
Plasma
x
x
x
x
Adverse 
Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination18 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 18 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
142/Protocol BP39529, Version 6
Part 3 - Year 1 (cont.)
1
The participants must meet the following criteria to enter the Part 3: Having completed Part 2 (i.e., completed Week 104 visit) and having completed the 12 week 
treatment free follow up visit. 
2
Not needed for the participants who performed 12-week treatment free FUP visit less than 30 days from Part 3 Week 1 visit ago 
3
Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment. For all 
participants that have started dopaminergic treament MDS-UPDRS Part III and Part IV will be assessed approximately 12 hours (e.g., overnight) after last dose of 
dopaminergic treatment. MDS-UPDRS Part III will then be repeated at least 1 hour after dopaminergic treatment along with MDS-UPDRS Part IV and Digital Biomarker 
assessments.
4
Vital signs (including semi-supine blood pressure, respiratory rate and pulse rate) have to be monitored pre-infusion, every 15 minutes until the end of infusion, and 
thereafter, every 30 minutes until the infusion line is removed.  In order to assess for orthostatic hypotension, BP and pulse rate will be evaluated after 2 minutes of 
standing still (after the semi-supine measurement) at pre-dose and 1 hour after end of infusion.  Note:  any abnormal value in Vital Signs needs to be repeated for 
confirmation or intervention if needed. 
5
Including weight 
6
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit
7
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed 
remotely since the scheduled days will often fall between clinic visit days.
8
In Clinic Digital Biomarker Assessments only include the Full Active Test.
9
On Part 3 Week 1 ECG will be obtained pre-dose and at end of study drug infusion. For the Part 3 early termination/Part 3 FUP the ECG timing should be early in the 
visit to approximate the pre-dose measurements.  For all the designated visits, ECGs (12-lead ) will be performed in triplicate, 1-2 minutes apart within 5 minutes.
10
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic visit or 
within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes dopaminergic 
treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
11
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
12
Serum RO7046015 (PK sampling) will be collected just prior to dosing and at the end of the infusion; serum and plasma biomarkers samples will be collected just prior 
to dosing . At Part 3 early termination and Part 3 FUP: Serum RO7046015 (PK sampling) and serum & plasma biomarkers sampling will be collected anytime (all time 
points of collection to be recorded in CRF). 
13
On dosing days Serum anti-RO7046015 antibody samples will be collected prior to dosing.
14
For consented participants only. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after early termination.  LP should be performed in 
the morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters.  An aliquot of the CSF samples will be sent for local laboratory 
analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be sent for central biomarker assessment. Any remaining 
CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
15
Premedication guidance is given in Section 4.4.2.
16
Study drug should be given as IV infusion at the same infusion rate as the last infusion in Part 2.
17
Skin biopsy must be collected pre-dose if the sample is collected on visits with study drug administration.
18
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Part 3 Early Termination assessments and attend the 
Part 3 Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
19
Should not be performed if already collected within 3 months of Part 3 early termination. If a Dat-SPECT scan is required for Part 3 early termination, TSH and T4 
assessment should be performed prior to the scan.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
143/Protocol BP39529, Version 6
Part 3 - Year 1 (cont.)
20
While the patients can continue active and passive digital biomarker remote monitoring on a daily basis if they are willing, digital biomarker remote monitoring is 
mandatory only for 2 weeks every 3 months in Part 3. Active and passive digital biomarker remote monitoring is recommended to start the day after digital biomarker 
in-clinic assessments are scheduled (e.g. patient performs digital biomarker in-clinic assessments on Part 3 Day 1 and performs active and passive digital biomarker 
remote monitoring from Part 3 Day 2 to Part 3 Day 15).  
21
In case of Part 3 early termination, active and passive digital biomarker remote monitoring in treatment free follow up should start the day after digital biomarker in-
clinic Part 3 early termination assessments have been performed and should last for at least 14 days.  

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
144/Protocol BP39529, Version 6
Schedule of Assessments Part 3 - Year 2
Treatment 
Week
Part 3 Week 56 Part 3 Week 60 Part 3 Week 64 Part 3 Week 68 Part 3 Week 72 Part 3 Week 76 Part 3 Week 80 Part 3 Week 84 Part 3 Week 88 Part 3 Week 92 Part 3 Week 96
Part 3 Week 
100
Part 3 Week 
104
Unscheduled
Treatment Day
Day 392
Day 420
Day 448
Day 476
Day 504
Day 532
Day 560
Day 588
Day 616
Day 644
Day 672
Day 700
Day 728
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
15
16
17
18
19
20
21
22
23
24
25
26
27
Assessments
Modified 
Hoehn & Yahr
x
x
x
x
x
x
x
x
MDS-UPDRS 
(Parts I, II, III, 
IV)1
x
x
x
x
x
x
x
x
Vital Signs2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic 
BP2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical 
Examination 
(Full)3
x
x
x
x
x
Physical 
Examination 
(Abbreviated)4
x
x
Neurological 
Examination
x
x
x
x
x
x
CGII/PGIC
x
x
x
x
x
x
MoCA
x
x
x
x
x
x
C-SSRS (Since 
Last Visit)
x
x
x
x
x
x
PDQ-39
x
x
x
x
x
x
SCOPA-AUT
x
x
x
x
x
x
Schwab & 
England - ADL
x
x
x
x
x
x
PDSS-2
x
x
x
x
x
x
Digital 
Biomarker 
Remote 
Monitoring 
(incl. diary 
questions, 
HADS, PAC-
SYM, EQ-5D-
5L) 5
x16
x16
x16
x16
x
x17
x17
Digital 
Biomarker In-
Clinic 
Assessments 6
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
145/Protocol BP39529, Version 6
Part 3 - Year 2 (cont.)
Treatment 
Week
Part 3 Week 56 Part 3 Week 60 Part 3 Week 64 Part 3 Week 68 Part 3 Week 72 Part 3 Week 76 Part 3 Week 80 Part 3 Week 84 Part 3 Week 88 Part 3 Week 92 Part 3 Week 96
Part 3 Week 
100
Part 3 Week 
104
Unscheduled
Treatment Day
Day 392
Day 420
Day 448
Day 476
Day 504
Day 532
Day 560
Day 588
Day 616
Day 644
Day 672
Day 700
Day 728
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
15
16
17
18
19
20
21
22
23
24
25
26
27
Assessments
Triplicate ECG-
12 lead7
x
x
x
x
Pre dose 12-
Lead ECG
x
x
x
DaT-SPECT8
x
x15
MRI (safety & 
efficacy)8
x
x
x15
Hematology
x
x
x
x
x
x
x
x
Blood 
Chemistry and 
Lipids
x
x
x
x
x
x
Coagulation
x
x
x
x
x
x
TSH and T4
x
x
x15
Urinalysis
x
x
x
x
x
x
Pregnancy 
Test9
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum 
RO7046015 
(PK 
sampling)11
x
x
x
x
x
Serum and 
plasma 
Biomarker10
x
x
x
x
x
x
Serum Anti-
RO7046015 
Antibody11
x
x
x
x
x
Optional CSF 
via Lumbar 
Puncture 
(matching 
serum and 
plasma 
sample)12
x
x
x15
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
146/Protocol BP39529, Version 6
Part 3 - Year 2 (cont.)
Treatment 
Week
Part 3 Week 56 Part 3 Week 60 Part 3 Week 64 Part 3 Week 68 Part 3 Week 72 Part 3 Week 76 Part 3 Week 80 Part 3 Week 84 Part 3 Week 88 Part 3 Week 92 Part 3 Week 96
Part 3 Week 
100
Part 3 Week 
104
Unscheduled
Treatment Day
Day 392
Day 420
Day 448
Day 476
Day 504
Day 532
Day 560
Day 588
Day 616
Day 644
Day 672
Day 700
Day 728
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
15
16
17
18
19
20
21
22
23
24
25
26
27
Assessments
PreMedication -
Loratadine 
10mg PO, 
Acetaminophe
n 650 mg PO
x
Administration 
of Study 
Medication
x
x
x
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x13
x13
x
RBR - Optional 
Whole Blood 
RNA
x
x
x
x
RBR - Optional 
Whole Blood 
Plasma
x
x
x
x
Adverse 
Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
147/Protocol BP39529, Version 6
Part 3 - Year 2 (cont.)
1
Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment. For all 
participants that have started dopaminergic treament MDS-UPDRS Part III and Part IV will be assessed approximately 12 hours (e.g., overnight)after last dose of 
dopaminergic treatment. MDS-UPDRS Part III will then be repeated at least 1 hour after dopaminergic treatment along with MDS-UPDRS Part IV and Digital Biomarker 
assessments.
2
Vital signs (including semi-supine blood pressure, respiratory rate and pulse rate) have to be monitored pre-infusion, every 15 minutes until the end of infusion, and 
thereafter, every 30 minutes until the infusion line is removed.  In order to assess for orthostatic hypotension, BP and pulse rate will be evaluated after 2 minutes of 
standing still (after the semi-supine measurement) at pre-dose and 1 hour after end of infusion on subsequent dosing days.  Note: any abnormal value in Vital Signs 
needs to be repeated for confirmation or intervention if needed. 
3
Including weight 
4
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit.
5
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed 
remotely since the scheduled days will often fall between clinic visit days.
6
In Clinic Digital Biomarker Assessments only include the Full Active Test.
7
For the Part 3 early termination/Part 3 FUP the ECG timing should be early in the visit to approximate the pre-dose measurements.  For all the designated visits, ECGs 
(12-lead ) will be performed in triplicate, 1-2 minutes apart within 5 minutes.
8
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic visit or 
within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes dopaminergic 
treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
9
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
10
Serum and plasma biomarkers samples will be collected just prior to dosing. At Part 3 early termination and Part 3 FUP: anytime (all time points of collection to be 
recorded in CRF). 
11
On dosing days Serum RO7046015 (PK sampling) and serum anti-RO7046015 antibody samples will be collected prior to dosing. At Part 3 early termination and Part 3 
FUP: anytime (all time points of collection to be recorded in CRF).  
12
For consented participants only. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after the Part 3 Week 104 infusion and early 
termination.  LP should be performed in the morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters.  An aliquot of the CSF 
samples will be sent for local laboratory analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be sent for 
central biomarker assessment. Any remaining CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
13
Skin biopsy must be collected pre-dose if the sample is collected on visits with study drug administration.
14
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Part 3 Early Termination assessments and attend the 
Part 3 Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
15
Should not be performed if already collected within 3 months of Part 3 early termination. If a Dat-SPECT scan is required for Part 3 early termination, TSH and T4 
assessment should be performed prior to the scan.
16
While the patients can continue active and passive digital biomarker remote monitoring on a daily basis if they are willing, digital biomarker remote monitoring is 
mandatory only for 2 weeks every 3 months in Part 3. Active and passive digital biomarker remote monitoring is recommended to start the day after digital biomarker 
in-clinic assessments are scheduled. 
17
In case of Part 3 early termination, active and passive digital biomarker remote monitoring in treatment free follow up should start the day after digital biomarker in-
clinic Part 3 early termination assessments have been performed and should  last for at least 14 days.  

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
148/Protocol BP39529, Version 6
Schedule of Assessments Part 3 - Year 3
Treatment 
Week
Part 3 Week 
108
Part 3 Week 
112
Part 3 Week 
116
Part 3 Week 
120
Part 3 Week 
124
Part 3 Week 
128
Part 3 Week 
132
Part 3 Week 
136
Part 3 Week 
140
Part 3 Week 
144
Part 3 Week 
148
Part 3 Week 
152
Part 3 Week 
156
Unscheduled
Treatment Day
Day 756
Day 784
Day 812
Day 840
Day 868
Day 896
Day 924
Day 952
Day 980
Day 1008
Day 1036
Day 1064
Day 1092
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
28
29
30
31
32
33
34
35
36
37
38
39
40
Assessments
Modified 
Hoehn & Yahr
x
x
x
x
x
x
x
x
MDS-UPDRS 
(Parts I, II, III, 
IV)1
x
x
x
x
x
x
x
x
Vital Signs2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic 
BP2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical 
Examination 
(Full)3
x
x
x
x
x
Physical 
Examination 
(Abbreviated)4
x
x
Neurological 
Examination
x
x
x
x
x
x
CGII/PGIC
x
x
x
x
x
x
MoCA
x
x
x
x
x
x
C-SSRS (Since 
Last Visit)
x
x
x
x
x
x
PDQ-39
x
x
x
x
x
x
SCOPA-AUT
x
x
x
x
x
x
Schwab & 
England - ADL
x
x
x
x
x
x
PDSS-2
x
x
x
x
x
x
Digital 
Biomarker 
Remote 
Monitoring 
(incl. diary 
questions, 
HADS, PAC-
SYM, EQ-5D-
5L) 5
x16
x16
x16
x16
x
x17
x17
Digital 
Biomarker In-
Clinic 
Assessments 6
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
149/Protocol BP39529, Version 6
Part 3 - Year 3 (cont.)
Treatment Week
Part 3 Week 
108
Part 3 Week 
112
Part 3 Week 
116
Part 3 Week 
120
Part 3 Week 
124
Part 3 Week 
128
Part 3 Week 
132
Part 3 Week 
136
Part 3 Week 
140
Part 3 Week 
144
Part 3 Week 
148
Part 3 Week 
152
Part 3 Week 
156
Unscheduled
Treatment Day
Day 756
Day 784
Day 812
Day 840
Day 868
Day 896
Day 924
Day 952
Day 980
Day 1008
Day 1036
Day 1064
Day 1092
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
28
29
30
31
32
33
34
35
36
37
38
39
40
Assessments
Triplicate ECG-
12 lead7
x
x
x
x
Pre dose 12-
Lead ECG
x
x
x
DaT-SPECT8
x15
MRI (safety & 
efficacy)8
x
x15
Hematology
x
x
x
x
x
x
x
x
Blood Chemistry 
and Lipids
x
x
x
x
x
x
Coagulation
x
x
x
x
x
x
TSH and T4
x
x
x15
Urinalysis
x
x
x
x
x
x
Pregnancy Test9
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum 
RO7046015 (PK 
sampling)10
x
x
x
x
x
Serum and 
plasma 
Biomarker10
x
x
x
x
x
x
Serum Anti-
RO7046015 
Antibody11
x
x
x
x
x
Optional CSF via 
Lumbar 
Puncture 
(matching serum 
and plasma 
sample)12
x
x15
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
150/Protocol BP39529, Version 6
Part 3 - Year 3 (cont.)
Treatment 
Week
Part 3 Week 
108
Part 3 Week 
112
Part 3 Week 
116
Part 3 Week 
120
Part 3 Week 
124
Part 3 Week 
128
Part 3 Week 
132
Part 3 Week 
136
Part 3 Week 
140
Part 3 Week 
144
Part 3 Week 
148
Part 3 Week 
152
Part 3 Week 
156
Unscheduled
Treatment Day
Day 756
Day 784
Day 812
Day 840
Day 868
Day 896
Day 924
Day 952
Day 980
Day 1008
Day 1036
Day 1064
Day 1092
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
28
29
30
31
32
33
34
35
36
37
38
39
40
Assessments
PreMedication -
Loratadine 
10mg PO, 
Acetaminophe
n 650 mg PO
x
Administration 
of Study 
Medication
x
x
x
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x13
x
RBR - Optional 
Whole Blood 
RNA
x
x
x
x
RBR - Optional 
Whole Blood 
Plasma
x
x
x
x
x
Adverse 
Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
151/Protocol BP39529, Version 6
Part 3 - Year 3 (cont.)
1
Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment. For all 
participants that have started dopaminergic treament MDS-UPDRS Part III and Part IV will be assessed approximately 12 hours (e.g. overnight) after last dose of 
dopaminergic treatment.  MDS-UPDRS Part III will then be repeated at least 1 hour after dopaminergic treatment along with MDS-UPDRS Part IV and Digital Biomarker 
assessments.
2
Vital signs (including semi-supine blood pressure, respiratory rate and pulse rate) have to be monitored pre-infusion, every 15 minutes until the end of infusion, and 
thereafter, every 30 minutes until the infusion line is removed. In order to assess for orthostatic hypotension, BP and pulse rate will be evaluated after 2 minutes of 
standing still (after the semi-supine measurement) at pre-dose and 1 hour after end of infusion on subsequent dosing days.  Note: any abnormal value in Vital Signs 
needs to be repeated for confirmation or intervention if needed. 
3
Including weight 
4
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit
5
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed 
remotely since the scheduled days will often fall between clinic visit days,
6
In Clinic Digital Biomarker Assessments only include the Full Active Test.
7
For the Part 3 early termination/Part 3 FUP the ECG timing should be early in the visit to approximate the pre-dose measurements.  For all the designated visits, ECGs 
(12-lead ) will be performed in triplicate, 1-2 minutes apart within 5 minutes.
8
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic visit or 
within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes dopaminergic 
treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
9
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
10
Serum and plasma biomarkers samples will be collected just prior to dosing. At Part 3 early termination and Part 3 FUP: anytime (all time points of collection to be 
recorded in CRF). 
11
On dosing days Serum RO7046015 (PK sampling) and serum anti-RO7046015 antibody samples will be collected prior to dosing. At Part 3 early termination and Part 3 
FUP: anytime (all time points of collection to be recorded in CRF).  
12
For consented participants. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after early termination. LP should be performed in the 
morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters. An aliquot of the CSF samples will be sent for local laboratory 
analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be sent for central biomarker assessment. Any remaining 
CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
13
Skin biopsy must be collected pre-dose if the sample is collected on visits with study drug administration
14
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Part 3 Early Termination assessments and attend the 
Part 3 Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
15
Should not be performed if already collected within 3 months of early termination. If a Dat-SPECT scan is required for early termination, TSH and T4 assessment should 
be performed prior to the scan.
16
While the patients can continue active and passive digital biomarker remote monitoring on a daily basis if they are willing, digital biomarker remote monitoring is 
mandatory only for 2 weeks every 3 months in Part 3. Active and passive digital biomarker remote monitoring is recommended to start the day after digital biomarker 
in-clinic assessments are scheduled.  
17
In case of Part 3 early termination, active and passive digital biomarker remote monitoring in treatment free follow up should start the day after digital biomarker in-
clinic Part 3 early termination assessments have been performed and should  last for at least 14 days.  

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
152/Protocol BP39529, Version 6
Schedule of Assessments Part 3 - Year 4
Treatment 
Week
Part 3 Week 
160
Part 3 Week 
164
Part 3 Week 
168
Part 3 Week 
172
Part 3 Week 
176
Part 3 Week 
180
Part 3 Week 
184
Part 3 Week 
188
Part 3 Week 
192
Part 3 Week 
196
Part 3 Week 
200
Part 3 Week 
204
Part 3 Week 
208
Unscheduled
Treatment Day
Day 1120
Day 1148
Day 1176
Day 1204
Day 1232
Day 1260
Day 1288
Day 1316
Day 1344
Day 1372
Day 1400
Day 1428
Day 1456
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
41
42
43
44
45
46
47
48
49
50
51
52
53
Assessments
Modified 
Hoehn & Yahr
x
x
x
x
x
x
x
x
MDS-UPDRS 
(Parts I, II, III, 
IV)1
x
x
x
x
x
x
x
x
Vital Signs2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic 
BP2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical 
Examination 
(Full)3
x
x
x
x
x
Physical 
Examination 
(Abbreviated)4
x
x
Neurological 
Examination
x
x
x
x
x
x
CGII/PGIC
x
x
x
x
x
x
MoCA
x
x
x
x
x
x
C-SSRS (Since 
Last Visit)
x
x
x
x
x
x
PDQ-39
x
x
x
x
x
x
SCOPA-AUT
x
x
x
x
x
x
Schwab & 
England - ADL
x
x
x
x
x
x
PDSS-2
x
x
x
x
x
x
Digital 
Biomarker 
Remote 
Monitoring 
(incl. diary 
questions, 
HADS, PAC-
SYM, EQ-5D-
5L) 5
x16
x16
x16
x16
x
x17
x17
Digital 
Biomarker In-
Clinic 
Assessments 6
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
153/Protocol BP39529, Version 6
Part 3 - Year 4 (cont.)
Treatment 
Week
Part 3 Week 
160
Part 3 Week 
164
Part 3 Week 
168
Part 3 Week 
172
Part 3 Week 
176
Part 3 Week 
180
Part 3 Week 
184
Part 3 Week 
188
Part 3 Week 
192
Part 3 Week 
196
Part 3 Week 
200
Part 3 Week 
204
Part 3 Week 
208
Unscheluded
Treatment Day
Day 1120
Day 1148
Day 1176
Day 1204
Day 1232
Day 1260
Day 1288
Day 1316
Day 1344
Day 1372
Day 1400
Day 1428
Day 1456
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
41
42
43
44
45
46
47
48
49
50
51
52
53
Assessments
Triplicate ECG-
12 lead7
x
x
x
x
Pre dose 12-
Lead ECG
x
x
x
DaT-SPECT8
x
x15
MRI (safety & 
efficacy)8
x
x
x15
Hematology
x
x
x
x
x
x
x
x
Blood 
Chemistry and 
Lipids
x
x
x
x
x
x
Coagulation
x
x
x
x
x
x
TSH and T4
x
x
x15
Urinalysis
x
x
x
x
x
x
Pregnancy 
Test9
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum 
RO7046015 
(PK 
sampling)10
x
x
x
x
x
Serum and 
plasma 
Biomarker10
x
x
x
x
x
x
Serum Anti-
RO7046015 
Antibody11
x
x
x
x
x
Optional CSF 
via Lumbar 
Puncture 
(matching 
serum and 
plasma 
sample)12
x
x
x15
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
154/Protocol BP39529, Version 6
Part 3 - Year 4 (cont.)
Treatment 
Week
Part 3 Week 
160
Part 3 Week 
164
Part 3 Week 
168
Part 3 Week 
172
Part 3 Week 
176
Part 3 Week 
180
Part 3 Week 
184
Part 3 Week 
188
Part 3 Week 
192
Part 3 Week 
196
Part 3 Week 
200
Part 3 Week 
204
Part 3 Week 
208
Unscheduled
Treatment Day
Day 1120
Day 1148
Day 1176
Day 1204
Day 1232
Day 1260
Day 1288
Day 1316
Day 1344
Day 1372
Day 1400
Day 1428
Day 1456
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
41
42
43
44
45
46
47
48
49
50
51
52
53
Assessments
PreMedication -
Loratadine 
10mg PO, 
Acetaminophe
n 650 mg PO
x
Administration 
of Study 
Medication
x
x
x
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x13
x13
x
RBR - Optional 
Whole Blood 
RNA
x
x
x
x
RBR - Optional 
Whole Blood 
Plasma
x
x
x
x
Adverse 
Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
155/Protocol BP39529, Version 6
Part 3 - Year 4 (cont.)
1
Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment. For all 
participants that have started dopaminergic treatment MDS-UPDRS Part III and Part IV will be assessed approximately 12 hours (e.g., overnight)after last dose of 
dopaminergic treatment. MDS-UPDRS Part III will then be repeated at least 1 hour after dopaminergic treatment along with MDS-UPDRS Part IV and Digital Biomarker 
assessments.
2
Vital signs (including semi-supine blood pressure, respiratory rate and pulse rate) have to be monitored pre-infusion, every 15 minutes until the end of infusion, and 
thereafter, every 30 minutes until the infusion line is removed.  In order to assess for orthostatic hypotension, BP and pulse rate will be evaluated after 2 minutes of 
standing still (after the semi-supine measurement) at pre-dose and 1 hour after end of infusion on subsequent dosing days.  Note: any abnormal value in Vital Signs 
needs to be repeated for confirmation or intervention if needed. 
3
Including weight 
4
Abbreviated physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit
5
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed 
remotely since the scheduled days will often fall between clinic visit days.
6
In Clinic Digital Biomarker Assessments only include the Full Active Test.
7
For the Part 3 early termination/Part 3 FUP the ECG timing should be early in the visit to approximate the pre-dose measurements. For all the designated visits, ECGs 
(12-lead) will be performed in triplicate, 1-2 minutes apart within 5 minutes.
8
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic visit or 
within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes dopaminergic 
treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
9
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
10
Serum and plasma biomarkers samples will be collected just prior to dosing. At Part 3 early termination and Part 3 FUP: anytime (all time points of collection to be 
recorded in CRF). 
11
On dosing days Serum RO7046015 (PK sampling) and serum anti-RO7046015 antibody samples will be collected prior to dosing. At Part 3 early termination and Part 3 
FUP: anytime (all time points of collection to be recorded in CRF).  
12
For consented participants only. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after the Week 312 infusion and early termination.  
LP should be performed in the morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters.  An aliquot of the CSF samples will 
be sent for local laboratory analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be sent for central biomarker 
assessment. Any remaining CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
13
Skin biopsy must be collected pre-dose if the sample is collected on visits with study drug administration
14
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Part 3 Early Termination assessments and attend the 
Part 3 Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
15
Should not be performed if already collected  within 3 months of Part 3 early termination. If a Dat-SPECT scan is required for Part 3 early termination, TSH and T4 
assessment should be performed prior to the scan.
16
While the patients can continue active and passive digital biomarker remote monitoring on a daily basis if they are willing, digital biomarker remote monitoring is 
mandatory only for 2 weeks every 3 months in Part 3. Active and passive digital biomarker remote monitoring is recommended to start the day after digital biomarker 
in-clinic assessments are scheduled  
17
In case of Part 3 early termination, active and passive digital biomarker remote monitoring in treatment free follow up should start the day after digital biomarker in-
clinic Part 3 early termination assessments have been performed and should  last for at least 14 days.  

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
156/Protocol BP39529, Version 6
Schedule of Assessments Part 3 - Year 5
Treatment 
Week
Part 3 Week 
212
Part 3 Week 
216
Part 3 Week 
220
Part 3 Week 
224
Part 3 Week 
228
Part 3 Week 
232
Part 3 Week 
236
Part 3 Week 
240
Part 3 Week 
244
Part 3 Week 
248
Part 3 Week 
252
Part 3 Week 
256
Part 3 Week 
260
Unscheduled
Treatment Day
Day 1484
Day 1512
Day 1540
Day 1568
Day 1596
Day 1624
Day 1652
Day 1680
Day 1708
Day 1736
Day 1764
Day 1792
Day 1820
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
54
55
56
57
58
59
60
61
62
63
64
65
66
Assessments
Modified 
Hoehn & Yahr
x
x
x
x
x
x
x
x
MDS-UPDRS 
(Parts I, II, III, 
IV)1
x
x
x
x
x
x
x
x
Vital Signs2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Orthostatic 
BP2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical 
Examination 
(Full)3
x
x
x
x
x
Physical 
Examination 
(Abbreviated)4
x
x
Neurological 
Examination
x
x
x
x
x
x
CGII/PGIC
x
x
x
x
x
x
MoCA
x
x
x
x
x
x
C-SSRS (Since 
Last Visit)
x
x
x
x
x
x
PDQ-39
x
x
x
x
x
x
SCOPA-AUT
x
x
x
x
x
x
Schwab & 
England - ADL
x
x
x
x
x
x
PDSS-2
x
x
x
x
x
x
Digital 
Biomarker 
Remote 
Monitoring 
(incl. diary 
questions, 
HADS, PAC-
SYM, EQ-5D-
5L) 5
x16
x16
x16
x17
x
x17
x17
Digital 
Biomarker In-
Clinic 
Assessments 6
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

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157/Protocol BP39529, Version 6
Part 3 - Year 5 (cont.)
Treatment 
Week
Part 3 Week 
212
Part 3 Week 
216
Part 3 Week 
220
Part 3 Week 
224
Part 3 Week 
228
Part 3 Week 
232
Part 3 Week 
236
Part 3 Week 
240
Part 3 Week 
244
Part 3 Week 
248
Part 3 Week 
252
Part 3 Week 
256
Part 3 Week 
260
Unscheduled
Treatment Day
Day 1484
Day 1512
Day 1540
Day 1568
Day 1596
Day 1624
Day 1652
Day 1680
Day 1708
Day 1736
Day 1764
Day 1792
Day 1820
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
54
55
56
57
58
59
60
61
62
63
64
65
66
Assessments
Triplicate ECG-
12 lead7
x
x
x
x
x
Pre dose 12-
Lead ECG
x
x
DaT-SPECT8
x15
MRI (safety & 
efficacy)8
x
x15
Hematology
x
x
x
x
x
x
x
x
Blood 
Chemistry and 
Lipids
x
x
x
x
x
x
Coagulation
x
x
x
x
x
x
TSH and T4
x
x
x15
Urinalysis
x
x
x
x
x
x
Pregnancy 
Test9
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Serum 
RO7046015 
(PK 
sampling)10
x
x
x
x
x
Serum and 
plasma 
Biomarker10
x
x
x
x
x
x
Serum Anti-
RO7046015 
Antibody11
x
x
x
x
x
Optional CSF 
via Lumbar 
Puncture 
(matching 
serum and 
plasma 
sample)12
x
x15
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
158/Protocol BP39529, Version 6
Part 3 - Year 5 (cont.)
Treatment 
Week
Part 3 Week 
212
Part 3 Week 
216
Part 3 Week 
220
Part 3 Week 
224
Part 3 Week 
228
Part 3 Week 
232
Part 3 Week 
236
Part 3 Week 
240
Part 3 Week 
244
Part 3 Week 
248
Part 3 Week 
252
Part 3 Week 
256
Part 3 Week 
260
Unscheduled
Treatment Day
Day 1484
Day 1512
Day 1540
Day 1568
Day 1596
Day 1624
Day 1652
Day 1680
Day 1708
Day 1736
Day 1764
Day 1792
Day 1820
Visit Window
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 4 days
+/- 7 days
Dose Number
54
55
56
57
58
59
60
61
62
63
64
65
66
Assessments
PreMedication 
Loratadine 
10mg PO, 
Acetaminophe
n 650 mg PO
x
Administration 
of Study 
Medication
x
x
x
x
x
x
x
x
x
x
x
x
x
Skin Biopsy
x13
x
RBR - Optional 
Whole Blood 
RNA
x
x
x
x
RBR - Optional 
Whole Blood 
Plasma
x
x
x
x
Adverse 
Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Prior to Start 
of 
Dopaminergic/
Symptomatic 
PD Treatment 
(if occuring 
during Part 3)
Part 3 Early 
Termination14 
(if occuring 
during Part 3)
Part 3 12 Week 
Treatment Free 
FUP 14 (at end 
of study or if 
treatment 
terminated 
early in Part 3)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
159/Protocol BP39529, Version 6
Part 3 - Year 5 (cont.)
1
Hoehn & Yahr staging will be assessed as part of the MDS-UPDRS Part III. MDS-UPDRS Part IV will be done for all participants on dopaminergic treatment. For all 
participants that have started dopaminergic treament MDS-UPDRS Part III and Part IV will be assessed approximately 12 hours (e.g., overnight)after last dose of 
dopaminergic treatment. MDS-UPDRS Part III will then be repeated at least 1 hour after dopaminergic treatment along with MDS-UPDRS Part IV and Digital Biomarker 
assessments.
2
Vital signs (including semi-supine blood pressure, respiratory rate and pulse rate) have to be monitored pre-infusion, every 15 minutes until the end of infusion, and 
thereafter, every 30 minutes until the infusion line is removed.  In order to assess for orthostatic hypotension, BP and pulse rate will be evaluated after 2 minutes of 
standing still (after the semi-supine measurement) at pre-dose and 1 hour after end of infusion on subsequent dosing days.  Note: any abnormal value in Vital Signs 
needs to be repeated for confirmation or intervention if needed. 
3
Including weight 
4
Abbreviated  physical exam will include Head Ears Eyes Nose and Throat (HEENT), Heart & Lung exams and any complaints expressed by participant at visit.
5
The PROs (patient reported outcome) are scheduled at regular intervals and administered on the digital biomarker smartphone. The PROs will typically be completed 
remotely since the scheduled days will often fall between clinic visit days.
6
In Clinic Digital Biomarker Assessments only include the Full Active Test.
7
For the Part 3 early termination/Part 3 FUP the ECG timing should be early in the visit to approximate the pre-dose measurements. For all the designated visits, ECGs 
(12-lead ) will be performed in triplicate, 1-2 minutes apart within 5 minutes.
8
MRIs should be performed with a time window of +/- 14 days from the study visit. DaT-SPECT should be performed within -14/-5 days if done prior to the clinic visit or 
within +14 days if done after the visit clinic. Refer to protocol Section 4.6.1.9 for procedure to follow in preparation of scans. In case participant takes dopaminergic 
treatment, MRI should be performed in a practically defined off state (no dopaminergic medication taken at the day of evaluation).
9
Urine pregnancy test for female participants (based on participant age/menopausal status) performed prior to dosing and all DaT-SPECT Scans.
10
Serum and plasma biomarkers samples will be collected just prior to dosing. At Part 3 early termination and Part 3 FUP: anytime (all time points of collection to be 
recorded in CRF). 
11
On dosing days Serum RO7046015 (PK sampling) and serum anti-RO7046015 antibody samples will be collected prior to dosing. At Part 3 early termination and Part 3 
FUP: anytime (all time points of collection to be recorded in CRF).  
12
For consented participants only. The ideal collection time to perform Lumbar Puncture (LP) is between 48-72 hours after early termination. LP should be performed in 
the morning (between 8:00 and 12:00 hours) to minimize potential diurnal variation of CSF parameters.  An aliquot of the CSF samples will be sent for local laboratory 
analysis (erythrocyte and leukocyte cell counts, protein, and glucose) while the remainder of the sample will be sent for central biomarker assessment. Any remaining 
CSF aliquots will be stored for the Research Biosample Repository for patients participating in RBR.
13
Skin biopsy must be collected pre-dose if the sample is collected on visits with study drug administration.
14
If participant discontinues or withdraws from the study treatment prematurely, they should complete all of the Part 3 Early Termination assessments and attend the 
Part 3 Follow-up visit normally done at the end of the study, 12 weeks after the last dose of study medication.
15
Should not be performed if already collected within 3 months of Part 3 early termination. If a Dat-SPECT scan is required for Part 3 early termination, TSH and T4 
assessment should be performed prior to the scan.
16
While the patients can continue active and passive digital biomarker remote monitoring on a daily basis if they are willing, digital biomarker remote monitoring is 
mandatory only for 2 weeks every 3 months in Part 3. Active and passive digital biomarker remote monitoring is recommended to start the day after digital biomarker 
in-clinic assessments are scheduled.  
17
At Part 3 Week 260 or in case of Part 3 early termination, active and passive digital biomarker remote monitoring in treatment free follow up should start the day after 
digital biomarker in-clinic Part 3 Week 260 or Part 3 early termination assessments have been performed and should  last for at least 14 days.  

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
160/Protocol BP39529, Version 6
Appendix 4
Recommended Sequence of Study Assessments
A.
Screening
Written informed consent must be obtained before performing any study-specific 
screening tests or evaluation and maintained at the study site.
The assessments required during screening can be performed throughout several visits 
to allow flexibility to the participants (3 in-clinic visits are acceptable). The following 
evaluations and procedures will be performed within 56 days prior to the first study drug 
administration (Baseline / Day 1):
Recommended sequence of assessments:
Screening Visit 1:

Signed Informed Consent

Demography

Medical history including diagnosis and duration of PD

Modified H&Y (Note: original H&Y stage is used for eligibility determination)

Vital signs including temperature, pulse rate, respiratory rate, and BP

Orthostatic Blood Pressure

Physical examination (full)

Neurological examination

ECG

Blood tests 
o
Hematology, chemistry (including fasting glucose), lipids, 
coagulation, TSH, T4, serology, serum pregnancy test (pre-
menopausal), FSH/LH/estradiol (post-menopausal)
o
Clinical genotyping
o
Optional whole blood sample (genetic), optional whole blood RNA, 
optional whole blood plasma

Urine tests (urinalysis, drugs of abuse/alcohol)

Adverse events

Previous and concomitant medication

MDS-UPDRS (Part I, II, III) (at least 7 days prior to Baseline visit) including H&Y 
staging

Review of Inclusion/Exclusion criteria (should be assessed throughout the visit and 
further assessments stopped if criteria not met)

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
161/Protocol BP39529, Version 6
Appendix 4
Recommended Sequence of Study Assessments (cont.)
Screening Visit 2 can be scheduled and take place immediately after (or on the same 
day as) Screening Visit 1, and before central reading results for safety labs and ECG are 
available, if no relevant eligibility concern arose at the end of Screening Visit 1 (e.g., no 
complex medical history requiring laboratory or ECG confirmatory results).
If the patient had normal MRI result within 6 months of the screening visit, the study MRI 
and Dat-SPECT can be scheduled on the same day at investigator’s discretion.
Screening Visit 2:

C-SSRS 

SCOPA-AUT

PDQ-39

RBDSQ

MMSE

MoCA

Provision of smartphone and wrist-worn wearable and training of participants for 
remote Digital Biomarker Remote Monitoring

Digital Biomarker In-Clinic Assessments including Active Test, selected items from 
the Berg Balance Scale and the Timed Up and Go test (at least 7 days prior to 
Baseline visit)

Adverse events

Review of Inclusion/Exclusion criteria (should be assessed throughout the visit and 
further assessments stopped if criteria not met)

Skin punch biopsy

Brain MRI (should only be performed after all other inclusion and exclusion have 
been reviewed and none exclude the participant from the trial, except DaT-SPECT 
which should be the final assessment)
Screening Visit 3:

DaT-SPECT (Note: it should be the last screening assessment)
Remote visit (phone call), after all Screening data available:

Adverse events

Final review of Review of Inclusion/Exclusion criteria (once DaT-SPECT results are 
received) and confirmation of eligibility or non-eligibility to the participant

Note: The smartphone and wrist-worn wearable must be returned to the clinic if the 
participant does not meet eligibility criteria

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
162/Protocol BP39529, Version 6
Appendix 4
Recommended Sequence of Study Assessments (cont.)
Baseline Lumbar Puncture assessment:

The lumbar puncture can be performed anytime during screening including at a 
planned screening visit and does not require a separate visit as long as it is done at 
least 4 days before Baseline/Day 1 visit and, if performed after the DAT-SPECT, 
must be at least 5 days after the scan.
B.
Dosing Days
At Dosing Visits, the sequence of assessments described below is recommended
for the assessments applicable to the specific study days:
Breaks and Lunch should be planned as well throughout the visits whenever deemed 
necessary or requested by the participants.

Prior to in-clinic visits with digital biomarker in-clinic assessments: Patients 
should be reminded by a phone call prior to the in-clinic visit to bring their 
Smartphone to the next in-clinic visit. 

If on dopaminergic treatment, they should also be reminded to refrain from taking 
their medication at home on specific clinic days when MDS-UPDRS will be 
performed, and bring their medication to the next in-clinic visit.  

Patient Global Impression of Change (PGIC)

Modified H&Y (should be performed by the same rater as MDS-UPDRS)

MDS-UPDRS (I, II, III, IV). should be performed at approximately the same time at 
each relevant visit
o
Part IV is only performed with participants who have started 
dopaminergic treatment (levodopa or dopamine agonists) 

Clinical Global Impression - Severity (CGI-S) (should be performed by the same 
rater as MDS-UPDRS, only at baseline)

Clinical Global Impression - Improvement (CGI-I) (should be performed by the same 
rater as MDS-UPDRS)

C-SSRS

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
163/Protocol BP39529, Version 6
Appendix 4
Recommended Sequence of Study Assessments (cont.)

Patient-reported outcomes / Neuropsychological tests
o
SCOPA-AUT
o
PDSS-2
o
PDQ-39
o
SE-ADL
o
MoCA
o
Digital Biomarker In-Clinic Assessments including Active Tests, 
selected items from the Berg Balance Scale and the Timed Up and 
Go test 

Dopaminergic treatment administration for participants who have started 
dopaminergic treatment

Clinical assessments 
o
Concomitant medications
o
Neurological / physical examinations
o
Vital signs pre-dose
o
Urinalysis, Pregnancy test
o
Adverse Events
o
Skin Punch Biopsy (pre-dose)
o
ECG pre-dose
o
Blood draws (PK sampling pre-dose, serum anti-RO7046015 
antibody, safety samples)
o
Pre-medication - required 30-60 minutes prior to first 3 infusions in 
Part 1 and Part 2; 
o
Drug infusion (2 hours for first 3 infusions); vital signs to be 
measured during infusion
o
Blood draw (PK sampling post dosing using a cannula different from 
the infusion cannula)
o
Vital signs post-dose
o
ECG post-dose
o
MDS-UPDRS Parts III and Digital Biomarker In-Clinic Assessments 
including Active Tests, selected items from the Berg Balance Scale 
and the Timed Up and Go test – for participants receiving 
dopaminergic treatment, at least 1 hour after receiving dopaminergic 
treatment, as described in Section 4.6.1.9

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
164/Protocol BP39529, Version 6
Appendix 4
Recommended Sequence of Study Assessments (cont.)
Notes regarding MRI, DaT-SPECT, Lumbar Puncture, Skin Punch Biopsy:

A urine pregnancy test must be performed in women of childbearing potential prior 
to the DaT-SPECT scan

All biosamples (serum, plasma, CSF, skin) should not be collected within 5 days 
after a DaT-SPECT. If serum, CSF or skin collection are planned on the same day, 
they must be performed prior to the DaT-SPECT 

If MRI and DaT-SPECT scans are performed on the same day, MRI must be 
performed first

MRI and DaT-SPECT may be performed on a different day than the regular dosing 
visit (within the time windows allowed in the Schedule of Assessments) to minimize 
the visit duration, as follows:
o
MRI may be performed within 14 days of the clinic visit specified in the 
SoA
o
DaT-SPECT should be performed within -14/-5 days if done prior to the 
visit clinic or within 14 days if done after the visit clinic 

For participants receiving dopaminergic treatment, MRI should be done ‘Off-state’ 
(no dopaminergic treatment taken on the day of MRI)

For participants consenting to CSF sampling:
o
Baseline lumbar puncture (LP) should be performed prior to Day -4 to 
allow recovery before first dosing. 
o
The post-baseline LP must be done 4872 hours after the drug 
infusion and can be done on the same day as MRI or DaT-SPECT 
(but this is not mandatory). In this case, the LP must be performed at 
least 3-4 hours prior to the scans. During these 3-4 hours, if the scan 
facility is located at the site, the cognitive assessments may be 
completed.

RO7046015/prasinezumab —F. Hoffmann-La Roche Ltd
165/Protocol BP39529, Version 6
Appendix 5
Patient Engagement Application
The Patient Engagement Application is a Smartphone system, referred to as an “app” 
that can be used by a patient or the legally authorized representative of a patient in the 
BP39529 study. 
The app is an optional service that patients can opt-in to use to remind them of 
activities/task relevant to study compliances like when to take their study medication, 
attend site visit, track goals. The app also provides supportive guides to help volunteers 
be aware of visit procedures, study information and instructions.
The app’s interactive features are intended to be a companion to the user during the 
course of a trial and include the following modules:

Study Information: targeted study information throughout the duration of the study.

Visit Schedule: site visit reminder based on predefined Schedule of Assessments 

Goals: ability to implement study defined or personal goal targets (e.g., weight, 
exercise, sleep, etc.).

Reminders: reminders for activities/task relevant to study compliances.

Site Information: module where patients can enter their site contacts details.
The app is available for download to smartphone devices that support iOS or Android. 
The app will contain study-specific information only once activated by a patient. The 
study coordinator will provide the patient with a secure activation code, which they can 
use to activate the app upon their first use.
The app does not collect any participant-identified information or clinical data. It cannot 
be installed on the phone provided by the Sponsor for conducting the digital biomarker 
assessments. This app is intended for informational purposes only. It is not a substitute 
for professional medical advice. Participants should contact the study site investigator or 
coordinator with any medical questions or concerns.