A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122/DNL151 in Participants With Parkinson's Disease and Pathogenic LRRK2 Variants
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 7
- 试验地点
- 27
- 主要终点
- Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III
研究概览
简要总结
In this study, researchers will learn more about a study drug called BIIB122 in participants with early-stage Parkinson's disease (PD). The study will focus on participants with a specific genetic variant in their LRRK2 gene.
The main question researchers are trying to answer is if taking BIIB122 slows the worsening of PD more than placebo in the early stages of PD.
To help answer this question, researchers will use a questionnaire called the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, also known as the MDS-UPDRS.
- The MDS-UPDRS measures impairment and disability in people living with PD. It was created in the 1980s and is one of the most used rating scales for PD symptoms.
- The MDS-UPDRS has 4 parts, and a higher score means more severe PD symptoms.
- Part I assesses non-motor experiences of daily living, including but not limited to memory loss, problems sleeping, pain, depression, and anxiety.
- Part II measures motor experiences of daily living.
- Part III is the results of a motor symptoms exam by a medical professional.
- Part IV records PD complications caused by motor symptoms.
Researchers will also learn more about the safety of BIIB122.
A description of how the study will be done is given below.
- Participants will take BIIB122 or a placebo as tablets by mouth. A placebo looks like the study drug but contains no real medicine.
- Participants will be in the study for 103 weeks to 187 weeks. This includes the screening and follow-up periods.
- Participants will take BIIB122 or placebo 1 time a day for 96 to 180 weeks.
- Participants can continue to take certain medications for PD. Participants must be on the same dose of medication for at least 90 days before the study begins.
- Participants will visit the clinic less often as the study continues, ranging every 4 weeks to every 24 weeks.
详细描述
BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of LRRK2 kinase
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 5 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis
- •Modified Hoehn and Yahr scale (mHY), Stages 1 to 2.5 (in OFF state), inclusive, at Screening
- •MDS-UPDRS Parts II and III (in OFF state) combined score ≤40 at Screening
- •Screening genetic test results verifying the presence of a pathogenic leucine-rich repeat kinase 2 (LRRK2) variant
排除标准
- •Clinically significant neurologic disorder other than PD, including, but not limited to, stroke, dementia, or seizure within 5 years of Screening Visit, in the opinion of the Investigator
- •Clinical evidence of atypical parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced parkinsonism
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
BIIB122 225 mg
Participants will receive 225 mg of BIIB122 tablets, orally, once daily (QD) for up to 180 weeks.
干预措施: BIIB122 (Drug)
BIIB122-Matching Placebo
Participants will receive BIIB122-matching placebo tablets, orally, QD for up to 180 weeks.
干预措施: BIIB122-Matching Placebo (Drug)
结局指标
主要结局
Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III
时间窗: From Week 96 to Week 180
Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (range 0-132). Part III contains 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. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (range 0-184). A higher score indicates more severe symptoms of Parkinson's disease (PD).
次要结局
- Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score(From Week 96 to Week 180)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose (Day 1) of the study drug up to the end of follow-up (up to 336 days))
- Time to Confirmed Worsening in MDS-UPDRS Part II Score(From Week 96 to Week 180)
- Change From Baseline in MDS-UPDRS Parts II and III Combined Score at Week 96(Baseline, Week 96)
- Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score at Week 96(Baseline, Week 96)