A Study to Assess if BIIB122 Tablets Are Safe and Can Slow Worsening of Early-Stage Parkinson's Disease in Participants With Specific LRRK2 Genetic Variants Between the Ages of 30 and 80 Using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale

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.

BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of LRRK2 kinase

Eligibility Criteria:
Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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.