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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03100149
Recruitment Status : Active, not recruiting
First Posted : April 4, 2017
Results First Posted : February 8, 2021
Last Update Posted : August 31, 2022
Sponsor:
Collaborator:
Prothena Biosciences Limited
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: RO7046015
Drug: Placebo
Enrollment 316
Recruitment Details Participants were enrolled at 57 sites in 5 different countries. 1 site had only 1 screen failure and no active participants were enrolled there.
Pre-assignment Details 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)
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description

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.

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.

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.

Period Title: Overall Study
Started 105 105 106
Completed [1] 105 101 104
Not Completed 0 4 2
Reason Not Completed
Adverse Event             0             1             0
Participant Moved out of Country             0             0             1
Withdrawal by Subject             0             3             1
[1]
Completed Part 1
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose Total
Hide Arm/Group Description

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.

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.

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 of all reporting groups
Overall Number of Baseline Participants 105 105 106 316
Hide Baseline Analysis Population Description
The modified intent-to-treat (mITT) population includes all participants randomized in the study who received any amount of study drug treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 105 participants 105 participants 106 participants 316 participants
59.9  (8.7) 60.3  (8.8) 59.4  (9.8) 59.9  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 106 participants 316 participants
Female
34
  32.4%
34
  32.4%
35
  33.0%
103
  32.6%
Male
71
  67.6%
71
  67.6%
71
  67.0%
213
  67.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 106 participants 316 participants
Asian
1
   1.0%
0
   0.0%
0
   0.0%
1
   0.3%
Black or African American
0
   0.0%
2
   1.9%
0
   0.0%
2
   0.6%
White
91
  86.7%
83
  79.0%
89
  84.0%
263
  83.2%
Unknown
13
  12.4%
20
  19.0%
17
  16.0%
50
  15.8%
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 76 74 73
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
9.37  (1.221) 7.35  (1.225) 8.75  (1.234)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2385
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -2.02
Confidence Interval (2-Sided) 80%
-4.21 to 0.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7169
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.62
Confidence Interval (2-Sided) 80%
-2.82 to 1.58
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.71
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 76 74 73
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Part IA -0.19  (0.119) -0.27  (0.119) -0.10  (0.121)
Part IB 0.94  (0.247) 0.90  (0.248) 0.96  (0.251)
Part I total 0.77  (0.295) 0.59  (0.297) 0.89  (0.300)
Part II total 2.75  (0.373) 3.09  (0.375) 2.69  (0.376)
Part III total 5.57  (0.897) 3.69  (0.900) 4.55  (0.911)
Part III subscore - rigidity 0.61  (0.263) 0.70  (0.265) 0.86  (0.268)
Part III subscore - bradykinesia 2.79  (0.556) 1.72  (0.560) 2.35  (0.565)
Part III subscore - resting tremor 1.20  (0.231) 0.59  (0.233) 0.79  (0.234)
Part III subscore - axial symptoms 0.19  (0.077) 0.11  (0.078) 0.18  (0.079)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part IA
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6116
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.08
Confidence Interval (2-Sided) 80%
-0.30 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.165
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part IA
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6188
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.08
Confidence Interval (2-Sided) 80%
-0.13 to 0.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.165
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part IB
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9062
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.04
Confidence Interval (2-Sided) 80%
-0.48 to 0.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.345
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part IB
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9621
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.02
Confidence Interval (2-Sided) 80%
-0.43 to 0.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.347
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part I Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6510
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.19
Confidence Interval (2-Sided) 80%
-0.71 to 0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.411
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part I Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7709
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.12
Confidence Interval (2-Sided) 80%
-0.41 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.413
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part II Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5177
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.34
Confidence Interval (2-Sided) 80%
-0.33 to 1.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.523
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part II Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9095
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.06
Confidence Interval (2-Sided) 80%
-0.73 to 0.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.523
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part III Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1354
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -1.88
Confidence Interval (2-Sided) 80%
-3.49 to -0.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.255
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part III Total
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4217
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -1.02
Confidence Interval (2-Sided) 80%
-2.64 to 0.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.262
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part III Subscore: Rigidity
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8053
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.09
Confidence Interval (2-Sided) 80%
-0.38 to 0.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.369
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part III Subscore: Rigidity
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4970
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.25
Confidence Interval (2-Sided) 80%
-0.22 to 0.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.370
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part III Subscore: Bradykinesia
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1703
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -1.07
Confidence Interval (2-Sided) 80%
-2.07 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.779
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part III Subscore: Bradykinesia
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5729
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.44
Confidence Interval (2-Sided) 80%
-1.45 to 0.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.782
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part III Subscore: Resting Tremor
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0628
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.61
Confidence Interval (2-Sided) 80%
-1.02 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.324
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part III Subscore: Resting Tremor
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2125
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.41
Confidence Interval (2-Sided) 80%
-0.82 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.325
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments MDS-UPDRS Part III Subscore: Axial Symptoms
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4577
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.08
Confidence Interval (2-Sided) 80%
-0.22 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.108
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments MDS-UPDRS Part III Subscore: Axial Symptoms
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9182
Comments Nominal p-values are displayed for descriptive purposes only.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.01
Confidence Interval (2-Sided) 80%
-0.15 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.109
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 102 100 104
Least Squares Mean (Standard Error)
Unit of Measure: Striatal Binding Ratio (SBR)
-0.08  (0.018) -0.10  (0.018) -0.11  (0.018)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3582
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 80%
-0.05 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1955
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 80%
-0.06 to 0.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Montreal Cognition Assessment (MoCA) Total Score
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 104 100 103
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
0.07  (0.177) 0.30  (0.181) 0.51  (0.178)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3611
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.22
Confidence Interval (2-Sided) 80%
-0.09 to 0.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.245
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0727
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.44
Confidence Interval (2-Sided) 80%
0.13 to 0.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.243
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Score
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 76 72 72
Measure Type: Number
Unit of Measure: Percentage of participants
Progressors 56.6 50.0 48.6
Responders 43.4 50.0 51.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4265
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 80%
0.50 to 1.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4063
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.76
Confidence Interval (2-Sided) 80%
0.49 to 1.16
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Patient Global Impression of Change (PGIC) Score
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 74 73 71
Measure Type: Number
Unit of Measure: Percentage of participants
Progressors 58.1 50.7 53.5
Responders 41.9 49.3 46.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3847
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.75
Confidence Interval (2-Sided) 80%
0.48 to 1.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7055
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 80%
0.57 to 1.36
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Schwab and England Activity of Daily Living (SE-ADL) Score
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 104 102 103
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-1.83  (0.644) -2.56  (0.650) -2.50  (0.647)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4142
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.73
Confidence Interval (2-Sided) 80%
-1.87 to 0.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.888
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4486
Comments Nominal p-values are displayed for descriptive purposes only.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.67
Confidence Interval (2-Sided) 80%
-1.81 to 0.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.885
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Time to Worsening in Motor or Non-Motor Symptoms
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 105 105 106
Median (80% Confidence Interval)
Unit of Measure: Days
174.0
(168.0 to 225.0)
169.0
(117.0 to 173.0)
170.0
(168.0 to 222.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3769
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 80%
0.94 to 1.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1658
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 80%
1.02 to 1.53
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Start of Dopaminergic Parkinson's Disease Treatment
Hide Description This endpoint is defined as the time between first dose of study medication and the date when the participant starts dopaminergic treatment.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 105 105 106
Median (80% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
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.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9542
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 80%
0.77 to 1.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1: RO7046015 High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4567
Comments Nominal p-values are displayed for descriptive purposes only.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 80%
0.63 to 1.13
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Hide Description 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.
Time Frame From baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants receiving any dose of the study drug were included in the safety analysis.
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 105 105 106
Measure Type: Number
Unit of Measure: Percentage of participants
AEs 82.9 93.3 91.5
SAEs 4.8 6.7 7.5
11.Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7046015
Hide Description 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.
Time Frame 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)
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Systemic Clearance (CL) of RO7046015
Hide Description Clearance is a measure of the rate at which a drug is removed from the body.
Time Frame 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)
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of RO7046015
Hide Description 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.
Time Frame 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)
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Area Under the Serum Concentration-Time Curve (AUC) of RO7046015 Over the Dosing Interval
Hide Description AUC is defined as the measure of RO7046015 plasma concentration over time.
Time Frame Baseline over the duration of the study
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of RO7046015 at Steady-state
Hide Description Cmax is the maximum observed plasma concentration of RO7046015.
Time Frame Baseline over the duration of the study
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Minimum Observed Serum Concentration (Ctrough) of RO7046015 at Steady-state
Hide Description Cmin is the minimum observed plasma concentration of RO7046015.
Time Frame Baseline over the duration of the study
Outcome Measure Data Not Reported
Time Frame Baseline up to Week 52
Adverse Event Reporting Description AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
 
Arm/Group Title Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Hide Arm/Group Description

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.

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.

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.

All-Cause Mortality
Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/105 (0.00%)      0/105 (0.00%)      0/106 (0.00%)    
Hide Serious Adverse Events
Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/105 (4.76%)      7/105 (6.67%)      8/106 (7.55%)    
Cardiac disorders       
Acute myocardial infarction  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
Cardiac failure  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Gastrointestinal disorders       
Inguinal hernia  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
General disorders       
Influenza like illness  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Infections and infestations       
Anal abscess  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/106 (0.94%)  1
Injury, poisoning and procedural complications       
Infusion related reaction  1  0/105 (0.00%)  0 0/105 (0.00%)  0 2/106 (1.89%)  2
Limb injury  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/106 (0.94%)  1
Radius fracture  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
Ulna fracture  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  0/105 (0.00%)  0 1/105 (0.95%)  1 1/106 (0.94%)  1
Ligament disorder  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Large intestine benign neoplasm  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/106 (0.00%)  0
Malignant melanoma  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Nervous system disorders       
Facial paralysis  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Parkinson's disease  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Transient ischaemic attack  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/106 (0.00%)  0
Psychiatric disorders       
Behaviour disorder  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/106 (0.94%)  1
Suicide attempt  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/106 (0.94%)  1
Renal and urinary disorders       
Nephrolithiasis  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/106 (0.94%)  1
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Placebo Part 1: RO7046015 Low Dose Part 1: RO7046015 High Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   57/105 (54.29%)      67/105 (63.81%)      69/106 (65.09%)    
Gastrointestinal disorders       
Constipation  1  6/105 (5.71%)  6 8/105 (7.62%)  8 10/106 (9.43%)  10
Nausea  1  9/105 (8.57%)  10 5/105 (4.76%)  6 9/106 (8.49%)  16
Infections and infestations       
Nasopharyngitis  1  15/105 (14.29%)  19 20/105 (19.05%)  25 13/106 (12.26%)  17
Upper respiratory tract infection  1  9/105 (8.57%)  10 4/105 (3.81%)  4 9/106 (8.49%)  11
Injury, poisoning and procedural complications       
Fall  1  5/105 (4.76%)  7 5/105 (4.76%)  9 10/106 (9.43%)  15
Infusion related reaction  1  17/105 (16.19%)  29 20/105 (19.05%)  40 35/106 (33.02%)  115
Musculoskeletal and connective tissue disorders       
Arthralgia  1  8/105 (7.62%)  9 7/105 (6.67%)  8 4/106 (3.77%)  4
Back pain  1  8/105 (7.62%)  9 8/105 (7.62%)  8 11/106 (10.38%)  13
Pain in extremity  1  2/105 (1.90%)  2 6/105 (5.71%)  7 5/106 (4.72%)  6
Nervous system disorders       
Headache  1  10/105 (9.52%)  12 10/105 (9.52%)  19 12/106 (11.32%)  15
Psychiatric disorders       
Anxiety  1  3/105 (2.86%)  3 2/105 (1.90%)  2 7/106 (6.60%)  7
Insomnia  1  5/105 (4.76%)  5 3/105 (2.86%)  3 8/106 (7.55%)  9
Skin and subcutaneous tissue disorders       
Dermatitis contact  1  6/105 (5.71%)  8 1/105 (0.95%)  1 3/106 (2.83%)  3
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03100149    
Other Study ID Numbers: BP39529
2017-000087-15 ( EudraCT Number )
First Submitted: March 29, 2017
First Posted: April 4, 2017
Results First Submitted: November 26, 2020
Results First Posted: February 8, 2021
Last Update Posted: August 31, 2022