An Exploratory Study of the Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons With REM Sleep Behavior Disorder (RBD)

Primary Objective: To assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration in persons with idiopathic REM Sleep Behavior Disorder (RBD). Secondary Objective, Safety: Safety will be assessed by monitoring the incidence of adverse events, clinical laboratory abnormalities, serious infections, signs and symptoms suggestive of new onset demyelinating disease, incidence of new demyelinating lesions on brain MRI scan and number of study participants who develop serum anti-adalimumab antibodies (ADAs). Secondary Objective, Clinical: To assess the effect of adalimumab treatment on change in clinical measures presumptively related to underlying neurodegeneration. The key secondary endpoint of interest will be a composite outcome. A study participant will be considered to have met the study endpoint upon the attainment of at least 1 of the following milestones at 2 consecutive study visits at least 3 months apart: * Increase from baseline of \> 2 points on the combined MDS-UPDRS Parts 1b and 2, OR * Increase from baseline in MDS-UPDRS Part III motor score \> 4 points, OR * Decrease from baseline in MoCA of \> 3 points, OR * Participant is diagnosed with PD, DLB, or MSA by a Movement Disorder specialist or a neurologist specializing in cognitive disorders, OR * Participant has initiated pharmacologic treatment for PD-, DLB-, or MSA-related symptoms Additional (or Exploratory) Objectives: * To evaluate the pharmacodynamic effect of adalimumab on biomarkers of immune system dysfunction in RBD patients to predict response to treatment * To evaluate the effect of adalimumab on selected biomarkers reflective of neurodegeneration * To evaluate effects of adalimumab treatment on selected measures of quality of life After a 12-week screening period, subjects will be randomized 1:1 to receive active or placebo treatment. Thereafter, subjects will be seen in clinic at 4, 12 and 24 weeks after their initial dose, and then at approximately 24-week intervals up to Week 96. A safety follow-up visit will occur 70 days after the last dose of study treatment. At specified visits, safety and clinical and biomarker assessments will be obtained, and study medication will be dispensed. Quantitative motor and cognitive assessments will be completed at home at intervals between in-person study visits. At 6-month intervals, subjects will be given a body-worn sensor that they will wear for 7 days to record patterns of activity during sleep and wakefulness. Subjects who meet one of the clinical secondary endpoints will remain in the study until its termination. Approximately 25 subjects in each treatment group will be enrolled in an Cerebrospinal Fluid (CSF) biomarker sub-study. Subjects in this sub-study: Individuals participating in the CSF sub-study will undergo lumbar punctures at baseline and at yearly intervals, thereafter, to assess the effects of adalimumab on biomarkers of immune processes and neurodegeneration in the CSF.