A Phase IIB, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 586
- 试验地点
- 197
- 主要终点
- DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
Participants will receive placebo as an IV infusion Q4W.
干预措施: Placebo (Drug)
Prasinezumab
Participants will receive an IV infusion of prasinezumab every 4 weeks (Q4W).
Participants will enter into the optional Open Label Extension (OLE) once the double-blind treatment period has completed.
干预措施: Prasinezumab (Drug)
结局指标
主要结局
DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- DBT Period: Number of Participants With Treatment Discontinuation Due to AEs(From study start to end of DBT period to at least 76 weeks)
- DBT Period: Number of Participants With Infusion Related Reactions (IRRs)(From study start to end of DBT period to at least 76 weeks)
- 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)
- DBT Period: Maximum Observed Concentration at Steady-state (Cmax,SS)(Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76)
- 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))
- 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))
- 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))
- 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))