Parkinsons Disease
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy and safety of intravenous (IV) prasinezumab versus placebo in participants with Early Parkinson's Disease (PD) who are on stable symptomatic PD medication.
Interventions
DRUGPrasinezumab
Prasinezumab will be administered as an IV infusion to participants Q4W.
DRUGPlacebo
Prasinezumab placebo will be administered to participants.
Sponsors
Hoffmann-La Roche
Prothena Biosciences Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of idiopathic PD based on MDS criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism * On symptomatic PD medication, with stable doses for at least 3 months prior to baseline * A diagnosis of PD for at least 3 months to maximum 3 years at screening * MDS-UPDRS Part IV score of 0 at screening and prior to randomization * Hoehn and Yahr (H\&Y) Stage I or II in OFF medication state at screening and prior to randomization * Dopamine transporter imaging with single photon emission computed tomography (DaT-SPECT) imaging consistent with dopamine transporter deficit, as assessed by the central reader * No anticipated changes in PD medication from baseline throughout the study duration based on clinical status during screening * Willingness and ability to use a smartphone application to measure PD-related symptoms for the duration of the study * Willingness and ability to wear a smartwatch to measure PD-related motor signs
Exclusion criteria
* Medical history indicating a Parkinsonian syndrome other than idiopathic PD * Diagnosis of PD dementia * Diagnosis of a significant neurologic disease other than PD * Within the last year, unstable or clinically significant cardiovascular disease * Uncontrolled hypertension * Drug and/or alcohol abuse within 12 months prior to screening, in the investigator's judgment (Nicotine is allowed, Marijuana use is not allowed) * Clinically significant abnormalities in laboratory test results at the screening visit, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis * Allergy to any of the components of prasinezumab, a known hypersensitivity, or a previous IRR following administration of any other monoclonal antibody * Any contraindications to obtaining a brain magnetic resonance imaging (MRI) * Any contraindications to DaT-SPECT imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | From study start to end of DBT period to at least 76 weeks | Time to confirmed motor progression event was the first time point of a worsening event defined as either \>= 5 points increase in MDS-UPDRS Part III score (assessed in "OFF" medication state) from baseline sustained over 2 consecutive assessments or a change in medication after first occurrence of \>= 5 points increase in MDS-UPDRS Part III score from baseline \& before follow-up assessment. MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event | From study start to end of DBT period to at least 76 weeks | Time to worsening of the motor function was defined as ≥3 points increase in MDS-UPDRS Part II score from baseline in the presence of a confirmed motor progression event. For the confirmed motor progression event the definition is as per primary endpoint definition. MDS-UPDRS Part II assesses motor experiences of daily living \& contained 13 questions answered by participant. For each question a numeric score is assigned between 0-4, 0 = Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Score range: 0 to 52 with higher score=severe impairment. |
| DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale | From study start to end of DBT period to at least 76 weeks | The PGI is a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (PGI-C) was intended to measure health state changes as reported by the participant on a 7-point scale (1=Very much improved to 7=Very much worse). The meaningfulness of the change was assessed and reported by the participant. |
| DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale | From study start to end of DBT period to at least 76 weeks | The CGI was a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (CGI-C) was intended to measure health state changes as reported by the clinician on a 7-point scale (1=Very much improved to 7=Very much worse). |
| DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score | From baseline up to Week 76 | MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment. |
| DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore | From baseline up to Week 76 | MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. For bradykinesia, subscore ranges from 0 to 52, while rigidity subscore ranges from 0 to 20, with higher scores indicating greater impairment. Change in bradykinesia and rigidity was assessed in "OFF" medication state. Adjusted mean is reported here. |
| DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From study start to end of DBT period to at least 76 weeks | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention. Number of participants with atleast 1 AE and SAE are reported here. |
| DBT Period: Number of Participants With Adverse Events of Special Interest (AESI) | From study start to end of DBT period to at least 76 weeks | An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated alanine transaminase (ALT) \& aspartate aminotransferase (AST) in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug. |
| DBT Period: Number of Participants With Treatment Discontinuation Due to AEs | From study start to end of DBT period to at least 76 weeks | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. |
| DBT Period: Number of Participants With Infusion Related Reactions (IRRs) | From study start to end of DBT period to at least 76 weeks | IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia. |
| DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | From study start to end of DBT period to at least 76 weeks | C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here. |
| DBT Period: Maximum Observed Concentration at Steady-state (Cmax,SS) | Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 | — |
| DBT Period: Minimum Observed Concentration at Steady-state (Cmin,SS) | Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 | — |
| DBT Period: Area Under the Serum Concentration Time Curve Over the Dosing Interval (AUCTau,SS) | Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 | — |
| DBT Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) at Baseline and Post-Treatment | From study start to end of DBT period to at least 76 weeks | — |
| OLE Period: Number of Participants With AEs and SAEs | From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months) | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention. |
| OLE Period: Number of Participants With AESI | From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months) | An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated ALT \& AST in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug. |
| OLE Period: Number of Participants With IRRs | From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months) | IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia. |
| DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV | From study start to end of DBT period to at least 76 weeks | MDS-UPDRS Part IV assessed motor complications of symptomatic treatment, dyskinesias, and motor fluctuations. The rater completed this assessment only for participants on L-Dopa treatment. |
| OLE Period: Number of Participants With in Suicidal Ideation, as Measured by the C-SSRS | From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months) | C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. |
Countries
Austria, Canada, France, Italy, Luxembourg, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 586 participants with early-stage Parkinson's disease (PD) took part in the study across 110 investigative sites in 9 countries. The study consisted of double-blind treatment (DBT), where participants were randomized in 1:1 ratio to receive prasinezumab or placebo and an optional open-label extension (OLE).
Pre-assignment details
After completing the DBT period, consenting & eligible participants entered the OLE period to receive prasinezumab. 3 participants in the prasinezumab arm and 1 participant in the placebo arm were randomized but not treated and 2 participants randomized to placebo arm received 1 dose of prasinezumab and were included in the prasinezumab arm for safety analysis. The study is still ongoing.
Participants by arm
| Arm | Count |
|---|---|
| DBT Period: Placebo Participants received prasinezumab matching placebo as an IV infusion, Q4W up to at least 76 weeks. | 293 |
| DBT Period: Prasinezumab Participants received prasinezumab, 1500 mg, as an IV infusion, Q4W up to at least 76 weeks. | 293 |
| Total | 586 |
Baseline characteristics
| Characteristic | DBT Period: Prasinezumab | Total | DBT Period: Placebo |
|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.2 | 64.2 years STANDARD_DEVIATION 7.3 | 64.4 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants | 64 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 241 Participants | 487 Participants | 246 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants | 35 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 25 Participants | 11 Participants |
| Race (NIH/OMB) White | 275 Participants | 553 Participants | 278 Participants |
| Sex: Female, Male Female | 110 Participants | 214 Participants | 104 Participants |
| Sex: Female, Male Male | 183 Participants | 372 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 290 | 1 / 292 |
| other Total, other adverse events | 205 / 290 | 206 / 292 |
| serious Total, serious adverse events | 34 / 290 | 34 / 292 |
Outcome results
Primary
DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III
Time to confirmed motor progression event was the first time point of a worsening event defined as either \>= 5 points increase in MDS-UPDRS Part III score (assessed in OFF medication state) from baseline sustained over 2 consecutive assessments or a change in medication after first occurrence of \>= 5 points increase in MDS-UPDRS Part III score from baseline & before follow-up assessment. MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | 49.7 weeks |
| DBT Period: Prasinezumab | DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | 61.1 weeks |
Comparison: Stratified Analysisp-value: 0.065795% CI: [0.69, 1.01]Log Rank
Secondary
DBT Period: Area Under the Serum Concentration Time Curve Over the Dosing Interval (AUCTau,SS)
Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76
Population: PAS included all randomized participants exposed to study treatment with sufficient dosing information and at least one adequately documented and quantifiable prasinezumab concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Area Under the Serum Concentration Time Curve Over the Dosing Interval (AUCTau,SS) | 49384 hours*microgram/milliter (h*µg/mL) |
Secondary
DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore
MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. For bradykinesia, subscore ranges from 0 to 52, while rigidity subscore ranges from 0 to 20, with higher scores indicating greater impairment. Change in bradykinesia and rigidity was assessed in OFF medication state. Adjusted mean is reported here.
Time frame: From baseline up to Week 76
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DBT Period: Placebo | DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore | 2.77 Units on a scale | Standard Error 0.476 |
| DBT Period: Prasinezumab | DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore | 2.85 Units on a scale | Standard Error 0.479 |
p-value: 0.895595% CI: [-1.08, 1.24]MMRM
Secondary
DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score
MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment.
Time frame: From baseline up to Week 76
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DBT Period: Placebo | DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score | 4.00 Units on a scale | Standard Error 0.592 |
| DBT Period: Prasinezumab | DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score | 3.61 Units on a scale | Standard Error 0.597 |
p-value: 0.594495% CI: [-1.84, 1.05]Mixed-model for Repeated Measures (MMRM)
Secondary
DBT Period: Maximum Observed Concentration at Steady-state (Cmax,SS)
Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76
Population: Pharmacokinetic (PK) Analysis Set (PAS) included all randomized participants exposed to study treatment with sufficient dosing information and at least one adequately documented and quantifiable prasinezumab concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Maximum Observed Concentration at Steady-state (Cmax,SS) | 313.5 micrograms/milliliter (µg/mL) |
Secondary
DBT Period: Minimum Observed Concentration at Steady-state (Cmin,SS)
Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76
Population: PAS included all randomized participants exposed to study treatment with sufficient dosing information and at least one adequately documented and quantifiable prasinezumab concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Minimum Observed Concentration at Steady-state (Cmin,SS) | 28.7 µg/mL |
Secondary
DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention. Number of participants with atleast 1 AE and SAE are reported here.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: Safety Analysis Set (SAS) included all participants who received at least one dose of study drug, with participants grouped according to treatment received. 3 participants in the prasinezumab arm and 1 participant in the placebo arm were randomized but not treated and 2 participants randomized to placebo arm received 1 dose of prasinezumab and were included in the prasinezumab arm for safety analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBT Period: Placebo | DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 260 Participants |
| DBT Period: Placebo | DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 34 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 267 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 34 Participants |
Secondary
DBT Period: Number of Participants With Adverse Events of Special Interest (AESI)
An AE was any untoward medical occurrence in participant administered a pharmaceutical product & which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated alanine transaminase (ALT) & aspartate aminotransferase (AST) in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: SAS included all participants who received at least one dose of study drug, with participants grouped according to treatment received. 3 participants in the prasinezumab arm and 1 participant in the placebo arm were randomized but not treated and 2 participants randomized to placebo arm received 1 dose of prasinezumab and were included in the prasinezumab arm for safety analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Number of Participants With Adverse Events of Special Interest (AESI) | 0 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With Adverse Events of Special Interest (AESI) | 0 Participants |
Secondary
DBT Period: Number of Participants With Infusion Related Reactions (IRRs)
IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: SAS included all participants who received at least one dose of study drug, with participants grouped according to treatment received. 3 participants in the prasinezumab arm and 1 participant in the placebo arm were randomized but not treated and 2 participants randomized to placebo arm received 1 dose of prasinezumab and were included in the prasinezumab arm for safety analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Number of Participants With Infusion Related Reactions (IRRs) | 37 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With Infusion Related Reactions (IRRs) | 32 Participants |
Secondary
DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a yes answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: SAS included all participants who received at least one dose of study drug, with participants grouped according to treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBT Period: Placebo | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Passive: Wish to be Dead | 6 Participants |
| DBT Period: Placebo | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Non-specific Active Suicidal Thoughts | 2 Participants |
| DBT Period: Placebo | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act | 3 Participants |
| DBT Period: Placebo | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior, no Suicidal Intent | 0 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior, no Suicidal Intent | 1 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Passive: Wish to be Dead | 5 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act | 0 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Non-specific Active Suicidal Thoughts | 2 Participants |
Secondary
DBT Period: Number of Participants With Treatment Discontinuation Due to AEs
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: SAS included all participants who received at least one dose of study drug, with participants grouped according to treatment received. 3 participants in the prasinezumab arm and 1 participant in the placebo arm were randomized but not treated and 2 participants randomized to placebo arm received 1 dose of prasinezumab and were included in the prasinezumab arm for safety analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Number of Participants With Treatment Discontinuation Due to AEs | 3 Participants |
| DBT Period: Prasinezumab | DBT Period: Number of Participants With Treatment Discontinuation Due to AEs | 2 Participants |
Secondary
DBT Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) at Baseline and Post-Treatment
Time frame: From study start to end of DBT period to at least 76 weeks
Population: Immunogenicity population included all participants on active treatment with at least one ADA assessment. Percentages have been rounded off.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) at Baseline and Post-Treatment | 0.3 percentage of participants |
Secondary
DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale
The CGI was a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (CGI-C) was intended to measure health state changes as reported by the clinician on a 7-point scale (1=Very much improved to 7=Very much worse).
Time frame: From study start to end of DBT period to at least 76 weeks
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale | 52.1 weeks |
| DBT Period: Prasinezumab | DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale | 60.6 weeks |
p-value: 0.062295% CI: [0.69, 1.01]Cox-regression adjusted
Secondary
DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale
The PGI is a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (PGI-C) was intended to measure health state changes as reported by the participant on a 7-point scale (1=Very much improved to 7=Very much worse). The meaningfulness of the change was assessed and reported by the participant.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale | 36.1 weeks |
| DBT Period: Prasinezumab | DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale | 44.4 weeks |
p-value: 0.157495% CI: [0.73, 1.05]Cox-regression adjusted
Secondary
DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV
MDS-UPDRS Part IV assessed motor complications of symptomatic treatment, dyskinesias, and motor fluctuations. The rater completed this assessment only for participants on L-Dopa treatment.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV | 91.1 weeks |
| DBT Period: Prasinezumab | DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV | 100.1 weeks |
p-value: 0.551595% CI: [0.75, 1.17]Cox-regression adjusted
Secondary
DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event
Time to worsening of the motor function was defined as ≥3 points increase in MDS-UPDRS Part II score from baseline in the presence of a confirmed motor progression event. For the confirmed motor progression event the definition is as per primary endpoint definition. MDS-UPDRS Part II assesses motor experiences of daily living & contained 13 questions answered by participant. For each question a numeric score is assigned between 0-4, 0 = Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Score range: 0 to 52 with higher score=severe impairment.
Time frame: From study start to end of DBT period to at least 76 weeks
Population: FAS included all randomized participants, with participants grouped according to their randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DBT Period: Placebo | DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event | 88.3 weeks |
| DBT Period: Prasinezumab | DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event | 112.1 weeks |
p-value: 0.091495% CI: [0.66, 1.03]Cox-regression adjusted
Secondary
OLE Period: Number of Participants With AEs and SAEs
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention.
Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)
Secondary
OLE Period: Number of Participants With AESI
An AE was any untoward medical occurrence in participant administered a pharmaceutical product & which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated ALT & AST in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug.
Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)
Secondary
OLE Period: Number of Participants With in Suicidal Ideation, as Measured by the C-SSRS
C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a yes answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior.
Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)
Secondary
OLE Period: Number of Participants With IRRs
IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia.
Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)