A Study to Assess the Safety of BIIB122 Tablets and if it Can Slow the Worsening of Early-Stage Parkinson's Disease in Participants Between the Ages of 30 and 80

Study Overview
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Brief Summary
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In this study, researchers will learn more about a study drug called BIIB122 in participants with early-stage Parkinson's disease (PD). In this study: Participants will take 225 milligrams (mg) of BIIB122 or a placebo as tablets by mouth. A placebo looks like the study drug but has no real medicine in it. Participants will take BIIB122 or placebo 1 time a day for up to a minimum of 48 weeks and a maximum of 144 weeks. Certain medications for PD will be allowed at enrollment for a subset of participants. The majority of clinic visits will be every 12 weeks. The main question researchers are trying to answer is if taking BIIB122 slows the worsening of symptoms 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. Researchers will use the MDS-UPDRS to learn about participant PD symptoms and how they affect their daily life. Researchers will also learn more about the safety of BIIB122.

Detailed Description
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BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2). Participants who completed the early termination (ET) visit of the study 283PD302 (NCT05418673) would be eligible for screening of this study and if enrolled, these participants are not eligible for the sub studies of 283PD201.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122 in Participants With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: BIIB122
* Drug: BIIB122-Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 2 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis Modified Hoehn and Yahr scale stages 1 to 2 (in OFF state), inclusive, at screening MDS-UPDRS Parts II and III (in OFF state) combined score less than or equal to (≤)40 at screening Key Exclusion Criteria: Clinically significant neurological 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. Montreal Cognitive Assessment (MoCA) score <24 at the screening visit. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB122 225 mg<br>Participants will receive BIIB122, 225 mg tablets, by mouth, once daily (QD) for up to a minimum of 48 weeks and a maximum of 144 weeks. Participants who received BIIB122 and completed the ET visit of study 283PD302 (NCT05418673) will continue to receive BIIB122, 225 mg tablets, by mouth, QD for up to a minimum of 48 weeks and a maximum of 144 weeks. | Drug: BIIB122<br>* Administered as specified in the treatment arm<br>* Other names: DNL151;|
| Placebo Comparator: BIIB122 Matching Placebo<br>Participants will receive BIIB122 matching placebo tablets, by mouth, QD for up to a minimum of 48 weeks and a maximum of 144 weeks. Participants who received placebo and completed the ET visit of study 283PD302 (NCT05418673) will continue to receive BIIB122 matching placebo tablets, by mouth, QD for up to a minimum of 48 weeks and a maximum of 144 weeks. | Drug: BIIB122-Matching Placebo<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score Over the Treatment Period | 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 PD. | Up to Week 144 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event. | Up to Week 146 | 
| Time to Confirmed Worsening in MDS-UPDRS Part II Score Over the Treatment Period | 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. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD. | Up to a minimum of 48 weeks and a maximum of 144 weeks | 
| Change From Baseline in MDS-UPDRS Parts II and III Combined Score | 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. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD. 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 Parts II and III combined score equals the sum of Part II and III (Range 0-184). A higher score indicates more severe symptoms of PD. | From Baseline up to Week 48 | 
| Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Over the Treatment Period | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. The mSE-ADL scale reflects the speed, ease, and independence with which an individual performs daily activities or personal chores with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence. The individual is asked to rate his or her function using an 11-point scale (10% increments), from 100% (completely independent; able to do all chores without slowness, difficulty, or impairment; essentially normal; unaware of any difficulty) to 0% (vegetative functions such as swallowing, bladder and bowels are not functioning; bedridden). The lower the score, the worse the functional status. | Up to a minimum of 48 weeks and a maximum of 144 weeks | 
| Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assesses non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and is assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which are to be completed by the participant (Range 0-28). 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 total score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicates more severe symptoms of PD. | From Baseline up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early-stage Parkinson Disease