Trial Outcomes & Findings for A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (NCT NCT03100149)

NCT ID: NCT03100149

Last Updated: 2026-01-09

Results Overview

The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of Parkinson's disease.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 316 participants
• Primary outcome timeframe: From baseline to Week 52
• Results posted on: 2026-01-09

Participant Flow

Participants were enrolled at 57 sites in 5 different countries. 1 site had only 1 screen failure and no active participants were enrolled there.

A total of 316 participants were randomized with a 1:1:1 allocation between the treatment groups (Placebo, Low-Dose prasinezumab and High-Dose prasinezumab)

Participant milestones

Measure	Part 1: Placebo Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Overall Study STARTED	105	105	106
Overall Study COMPLETED	105	101	104
Overall Study NOT COMPLETED	0	4	2

Reasons for withdrawal

Measure	Part 1: Placebo Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Overall Study Adverse Event	0	1	0
Overall Study Participant Moved out of Country	0	0	1
Overall Study Withdrawal by Subject	0	3	1

Baseline Characteristics

A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease

Baseline characteristics by cohort

Measure	Part 1: Placebo n=105 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.	Total n=316 Participants Total of all reporting groups
Age, Continuous	59.9 Years STANDARD_DEVIATION 8.7 • n=8 Participants	60.3 Years STANDARD_DEVIATION 8.8 • n=7 Participants	59.4 Years STANDARD_DEVIATION 9.8 • n=15 Participants	59.9 Years STANDARD_DEVIATION 9.1 • n=42 Participants
Sex: Female, Male Female	34 Participants n=8 Participants	34 Participants n=7 Participants	35 Participants n=15 Participants	103 Participants n=42 Participants
Sex: Female, Male Male	71 Participants n=8 Participants	71 Participants n=7 Participants	71 Participants n=15 Participants	213 Participants n=42 Participants
Race/Ethnicity, Customized Asian	1 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=8 Participants	2 Participants n=7 Participants	0 Participants n=15 Participants	2 Participants n=42 Participants
Race/Ethnicity, Customized White	91 Participants n=8 Participants	83 Participants n=7 Participants	89 Participants n=15 Participants	263 Participants n=42 Participants
Race/Ethnicity, Customized Unknown	13 Participants n=8 Participants	20 Participants n=7 Participants	17 Participants n=15 Participants	50 Participants n=42 Participants

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: The modified intent-to-treat (mITT) population includes all participants randomized in the study who received any amount of study drug treatment. Assessments of participants who started symptomatic therapy were included in the analysis up to the day before symptomatic treatment started.

The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of Parkinson's disease.

Outcome measures

Measure	Part 1: Placebo n=76 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=74 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=73 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52	9.37 Units on a scale Standard Error 1.221	7.35 Units on a scale Standard Error 1.225	8.75 Units on a scale Standard Error 1.234

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The modified intent-to-treat (mITT) population includes all participants randomized in the study who received any amount of study drug treatment. Assessments of participants who started symptomatic therapy were included in the analysis up to the day before symptomatic treatment started.

The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. There are 4 subscores in Part III: Bradykinesia, Rigidity, Resting tremors and Axial symptoms. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range:0-236). A higher score indicated more severe symptoms of Parkinson's disease.

Outcome measures

Measure	Part 1: Placebo n=76 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=74 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=73 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part IA	-0.19 Units on a scale Standard Error 0.119	-0.27 Units on a scale Standard Error 0.119	-0.10 Units on a scale Standard Error 0.121
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part IB	0.94 Units on a scale Standard Error 0.247	0.90 Units on a scale Standard Error 0.248	0.96 Units on a scale Standard Error 0.251
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part I total	0.77 Units on a scale Standard Error 0.295	0.59 Units on a scale Standard Error 0.297	0.89 Units on a scale Standard Error 0.300
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part II total	2.75 Units on a scale Standard Error 0.373	3.09 Units on a scale Standard Error 0.375	2.69 Units on a scale Standard Error 0.376
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part III total	5.57 Units on a scale Standard Error 0.897	3.69 Units on a scale Standard Error 0.900	4.55 Units on a scale Standard Error 0.911
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part III subscore - rigidity	0.61 Units on a scale Standard Error 0.263	0.70 Units on a scale Standard Error 0.265	0.86 Units on a scale Standard Error 0.268
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part III subscore - bradykinesia	2.79 Units on a scale Standard Error 0.556	1.72 Units on a scale Standard Error 0.560	2.35 Units on a scale Standard Error 0.565
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part III subscore - resting tremor	1.20 Units on a scale Standard Error 0.231	0.59 Units on a scale Standard Error 0.233	0.79 Units on a scale Standard Error 0.234
Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores Part III subscore - axial symptoms	0.19 Units on a scale Standard Error 0.077	0.11 Units on a scale Standard Error 0.078	0.18 Units on a scale Standard Error 0.079

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment and had no symptomatic PD treatment. The analysis included all assessments regardless of symptomatic treatment intake.

DaT-SPECT (dopamine transporter imaging with single photon emission computed tomography) is a dopamine transporter SPECT imaging that uses a radioactive agent called 123^I-ioflupane to quantify the density of the dopamine transporters in the striatum. Changes from baseline to week 52 in DaT-SPECT striatal binding ratios (SBRs; reference region: occipital cortex) in the putamen ipsilateral to the clinically most affected side were analyzed.

Outcome measures

Measure	Part 1: Placebo n=102 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=100 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=104 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Striatal Binding Ratio (SBR) in the Putamen Ipsilateral to the Clinically Most Affected Side	-0.08 Striatal Binding Ratio (SBR) Standard Error 0.018	-0.10 Striatal Binding Ratio (SBR) Standard Error 0.018	-0.11 Striatal Binding Ratio (SBR) Standard Error 0.018

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment and had no symptomatic PD treatment. The analysis included all assessments regardless of symptomatic treatment intake.

The Montreal Cognitive Assessment (MoCA) is a rapid screening that was developed to be more sensitive to participants presenting with mild cognitive complaints. It briefly assesses short term and working memory, visuospatial abilities, executive function, attention, concentration, language and orientation. Scores on the MoCA test range from 0-30. Higher scores are associated with better cognitive function.

Outcome measures

Measure	Part 1: Placebo n=104 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=100 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=103 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Montreal Cognition Assessment (MoCA) Total Score	0.07 Units on a scale Standard Error 0.177	0.30 Units on a scale Standard Error 0.181	0.51 Units on a scale Standard Error 0.178

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment. Assessments of participants who started symptomatic therapy were included in the analysis up to the day before symptomatic treatment started.

The CGI-I was intended as a measure of change in health status. CGI-I scores ranged from 1 (very much improved) through to 7 (very much worse). For the CGI-I, participants were divided into one of two groups, Responders or Progressors. Responders were scored on a scale of 1-4 which was rated as "no change", "minimally improved", "much improved" or "very much improved." Progressors were scored on a scale of 5-7 which was rated as "minimally worse", "much worse" or "very much worse." The percentage of participants rated by CGI-I Scale grouping at week 52 was analyzed using a logistic regression model.

Outcome measures

Measure	Part 1: Placebo n=76 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=72 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=72 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Score Progressors	56.6 Percentage of participants	50.0 Percentage of participants	48.6 Percentage of participants
Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Score Responders	43.4 Percentage of participants	50.0 Percentage of participants	51.4 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment. Assessments of participants who started symptomatic therapy were included in the analysis up to the day before symptomatic treatment started.

The PGIC was intended as a measure of change in health state from the participants perspective. PGIC scores ranged from 1 (very much improved) through to 7 (very much worse). For the PGIC, participants were divided into one of two groups, Responders or Progressors. Responders were scored on a scale of 1-4 which was rated as "no change", "minimally improved", "much improved" or "very much improved." Progressors were scored on a scale of 5-7 which was rated as "minimally worse", "much worse" or "very much worse." The percentage of participants rated by PGIC Scale grouping at week 52 was analyzed using a logistic regression model.

Outcome measures

Measure	Part 1: Placebo n=74 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=73 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=71 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Patient Global Impression of Change (PGIC) Score Progressors	58.1 Percentage of participants	50.7 Percentage of participants	53.5 Percentage of participants
Change From Baseline in Patient Global Impression of Change (PGIC) Score Responders	41.9 Percentage of participants	49.3 Percentage of participants	46.5 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment and had no symptomatic PD treatment. The analysis included all assessments regardless of symptomatic treatment intake.

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.

Outcome measures

Measure	Part 1: Placebo n=104 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=102 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=103 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Change From Baseline in Schwab and England Activity of Daily Living (SE-ADL) Score	-1.83 Units on a scale Standard Error 0.644	-2.56 Units on a scale Standard Error 0.650	-2.50 Units on a scale Standard Error 0.647

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment and had no symptomatic PD treatment. The analysis included all assessments regardless of symptomatic treatment intake.

This outcome measure is defined as the time to between first dose of study medication and the date when the particiapnt increases in MDS-UPDRS Part I (Range 0-52) of 3 or more points, or in MDS-UPDRS Part II (Range 0-52) of 3 or more points, whichever comes first. A higher score indicated more severe motor signs of Parkinson's disease.

Outcome measures

Measure	Part 1: Placebo n=105 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Time to Worsening in Motor or Non-Motor Symptoms	174.0 Days Interval 168.0 to 225.0	169.0 Days Interval 117.0 to 173.0	170.0 Days Interval 168.0 to 222.0

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: The mITT population includes all participants randomized in the study who received any amount of study drug treatment and had no symptomatic PD treatment. The analysis included all assessments regardless of symptomatic treatment intake.

This endpoint is defined as the time between first dose of study medication and the date when the participant starts dopaminergic treatment.

Outcome measures

Measure	Part 1: Placebo n=105 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Time to Start of Dopaminergic Parkinson's Disease Treatment	NA Days The median time to start of treatment" would be the timepoint when more than 50% of all participants started the treatment. At the end of Week 52, less than 50% of the participants started the treatment, thus the median time to start of treatment was not estimable.	NA Days The median time to start of treatment" would be the timepoint when more than 50% of all participants started the treatment. At the end of Week 52, less than 50% of the participants started the treatment, thus the median time to start of treatment was not estimable.	NA Days The median time to start of treatment" would be the timepoint when more than 50% of all participants started the treatment. At the end of Week 52, less than 50% of the participants started the treatment, thus the median time to start of treatment was not estimable.

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: All randomized participants receiving any dose of the study drug were included in the safety analysis.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was any AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Measure	Part 1: Placebo n=105 Participants Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 Participants Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 Participants Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AEs	82.9 Percentage of participants	93.3 Percentage of participants	91.5 Percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) SAEs	4.8 Percentage of participants	6.7 Percentage of participants	7.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Pre-dose (0 hours) on Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)

Samples of the participant's blood was taken to evaluate anti-drug antibodies (ADA). The number of ADA positive participants, Treatment-induced and Treatment-enhanced was reported. Treatment-induced = participants with ADA negative or missing data at baseline but develop an ADA response following exposure to the study drug. Treatment-enhanced = participants with ADA positive at baseline and the titre of one or more post-baseline samples is at least >=4 fold increase greater than the baseline titre sample.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Baseline, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)

Clearance is a measure of the rate at which a drug is removed from the body.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Baseline, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)

Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline over the duration of the study

AUC is defined as the measure of RO7046015 plasma concentration over time.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline over the duration of the study

Cmax is the maximum observed plasma concentration of RO7046015.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline over the duration of the study

Cmin is the minimum observed plasma concentration of RO7046015.

Outcome measures

Outcome data not reported

Adverse Events

Part 1: Placebo

Serious events: 5 serious events

Other events: 57 other events

Deaths: 0 deaths

Part 1: RO7046015 Low Dose

Serious events: 7 serious events

Other events: 67 other events

Deaths: 0 deaths

Part 1: RO7046015 High Dose

Serious events: 8 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1: Placebo n=105 participants at risk Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 participants at risk Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 participants at risk Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Cardiac disorders Acute myocardial infarction	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Cardiac disorders Cardiac failure	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Gastrointestinal disorders Inguinal hernia	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
General disorders Influenza like illness	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Infections and infestations Anal abscess	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	1.9% 2/106 • Number of events 2 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Limb injury	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Radius fracture	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Ulna fracture	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Musculoskeletal and connective tissue disorders Ligament disorder	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine benign neoplasm	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Nervous system disorders Facial paralysis	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Nervous system disorders Parkinson's disease	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Nervous system disorders Transient ischaemic attack	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/106 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Psychiatric disorders Behaviour disorder	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Psychiatric disorders Suicide attempt	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Renal and urinary disorders Nephrolithiasis	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.00% 0/105 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.94% 1/106 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.

Other adverse events

Measure	Part 1: Placebo n=105 participants at risk Participants received placebo as intravenous (IV) infusion every four weeks (Q4W) up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to placebo during Part 1 of the study will be rerandomized to one of the two active doses using a 1:1 allocation ratio. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 Low Dose n=105 participants at risk Participants received RO7046015 at a low dose level (1500 mg; for all body weights) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the low dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the low dose.	Part 1: RO7046015 High Dose n=106 participants at risk Participants received RO7046015 at a high dose level (3500 mg for body weight \<65 kilogram (kg) or 4500 mg for body weight \>=65 kg) as an IV infusion Q4W up to 52 weeks in Part 1. Part 2 of the study occurs from Weeks 56 to 104. Participants initially randomized to the high dose group will remain on their dose as assigned in Part 1. Part 2 is followed by 12 week termination follow-up safety visit and then by Part 3. Part 3 will last 260 weeks plus 12 weeks termination follow-up safety visit in which all participants will receive the high dose.
Infections and infestations Upper respiratory tract infection	8.6% 9/105 • Number of events 10 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	3.8% 4/105 • Number of events 4 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	8.5% 9/106 • Number of events 11 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Fall	4.8% 5/105 • Number of events 7 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	4.8% 5/105 • Number of events 9 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	9.4% 10/106 • Number of events 15 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Skin and subcutaneous tissue disorders Dermatitis contact	5.7% 6/105 • Number of events 8 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	0.95% 1/105 • Number of events 1 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	2.8% 3/106 • Number of events 3 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Infections and infestations Nasopharyngitis	14.3% 15/105 • Number of events 19 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	19.0% 20/105 • Number of events 25 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	12.3% 13/106 • Number of events 17 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Gastrointestinal disorders Constipation	5.7% 6/105 • Number of events 6 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	7.6% 8/105 • Number of events 8 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	9.4% 10/106 • Number of events 10 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Gastrointestinal disorders Nausea	8.6% 9/105 • Number of events 10 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	4.8% 5/105 • Number of events 6 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	8.5% 9/106 • Number of events 16 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Injury, poisoning and procedural complications Infusion related reaction	16.2% 17/105 • Number of events 29 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	19.0% 20/105 • Number of events 40 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	33.0% 35/106 • Number of events 115 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Musculoskeletal and connective tissue disorders Arthralgia	7.6% 8/105 • Number of events 9 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	6.7% 7/105 • Number of events 8 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	3.8% 4/106 • Number of events 4 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Musculoskeletal and connective tissue disorders Back pain	7.6% 8/105 • Number of events 9 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	7.6% 8/105 • Number of events 8 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	10.4% 11/106 • Number of events 13 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 2/105 • Number of events 2 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	5.7% 6/105 • Number of events 7 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	4.7% 5/106 • Number of events 6 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Nervous system disorders Headache	9.5% 10/105 • Number of events 12 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	9.5% 10/105 • Number of events 19 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	11.3% 12/106 • Number of events 15 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Psychiatric disorders Anxiety	2.9% 3/105 • Number of events 3 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	1.9% 2/105 • Number of events 2 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	6.6% 7/106 • Number of events 7 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
Psychiatric disorders Insomnia	4.8% 5/105 • Number of events 5 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	2.9% 3/105 • Number of events 3 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.	7.5% 8/106 • Number of events 9 • Baseline up to Week 52 AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER