A Study to Evaluate the Efficacy, PK, Safety, and Tolerability of VIM0423 in Adults With Parkinson's Disease Tremor Insufficiently Responsive to Dopaminergic Therapy

Parkinson's disease (PD) is the second most common neurodegenerative condition, with studies estimating US prevalence among individuals aged 45 years and older rising to approximately 1,238,000 by 2030. More than 75% of individuals with PD will experience resting tremor at some point during their disease course, and approximately 60% additionally suffer from a symptomatic tremor during action or movement, complicating functional tasks.

The distress caused by PD tremor is profound, with individuals consistently identifying it as their "most bothersome" symptom in early disease, and more impactful than other motor and nonmotor symptoms. Despite the clear importance of this symptom to patient experience, significant unmet need in tremor management persists. Tremor-specific efficacy of dopaminergic therapy, the mainstay of early PD pharmacology, is often inconsistent or incomplete, giving rise to the clinical concept of "dopamine-responsive" versus "dopamine-refractory" tremor. Anti-tremor efficacy of anticholinergic agents has been recognized for decades; however, their clinical utility is limited by both central and peripheral adverse effects. VIM0423 is being developed as an oral medication designed to improve the central and peripheral tolerability seen with other anticholinergic medications.

Vista PD (Study VIM0423-251) is a Phase 2, multicenter study designed to assess the efficacy, PK, safety, and tolerability of VIM0423 in adults with Parkinson's disease tremor insufficiently responsive to dopaminergic therapy. Up to 80 individuals will be enrolled in the trial.

Cohort 1 will be comprised of adults diagnosed with PD who are on stable and adequate dopaminergic therapy (oral levodopa or oral dopamine agonist only), with residual tremor. Participants in Cohort 1 will be randomized (1:1) to receive either VIM0423 or matching placebo (up to 5 pills a day \[MO1.1\] \[TG1.2\] \[MO1.3\], taken once daily) for 7 weeks. The Investigator and Participant will not know whether \[MO2.1\] patients are receiving VIM0423 or placebo, but that information will be available if needed.

Cohort 2 will be comprised of adults diagnosed with PD who are dopaminergic naïve, as defined by: no prior or ongoing usage of levodopa (in any form) or dopamine agonist (in any form), and no anticipated plans to initiate said therapies for the duration of the study. Participants in Cohort 2 will be randomized (1:1) to receive either VIM0423 or matching placebo (up to 5 pills a day \[MO3.1\], taken once daily) for 7 weeks. The Investigator and Participant will not know whether patients are receiving VIM0423 or placebo, but that information will be available if needed.

The total time of participation in the trial is up to 12 weeks and requires 6 in person visits. The study schedule includes Screening and Baseline (up to 4 weeks, 2 visits), Treatment period (including taper, 7 weeks, 3 Visits), and Safety follow-up (1 week, 1 Visit).

Assessments of changes in Parkinson's disease will be made by study personnel. Clinical labs, EKGs, and Adverse events will be monitored throughout the study. Participants will be asked to use a wearable device during the study and perform self-assessments of their Parkinson's tremor and its impact on their activities of daily living.

Participants receiving active (VIM0423) n\~25

Drug: VIM0423

Participants receiving placebo n\~25

Drug: VIM0423 Placebo

Participants receiving active (VIM0423) n\~15

Drug: VIM0423

Participants receiving placebo n\~15

Drug: VIM0423 Placebo

VIM0423 is a combination drug product containing two active ingredients (VMA-1001 and VMA-1002)

Matching VIM0423 placebo product containing no active ingredient

Time frame: From baseline to Week 6

The MDS-UPDRS is a multi-part assessment designed to evaluate various aspects of PD and its impact on the individual, including motor and non-motor symptoms. There are four parts, all of which will be completed in this study: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), Part III (motor examination), and Part IV (motor complications). Each part has varying maximum scores. In all cases, a higher score represents a more severe status.

Time frame: From baseline to Week 6

The CGI-S assesses the clinician's impression of the participant's current illness state. The clinician should use his/her total clinical experience with this population and rate the current severity of the participant's PD on a scale from 1 (normal, not at all ill) to 7 (among the most extremely ill).

Time frame: From baseline to Week 6

The TETRAS-ADL is a standardized assessment of the impact of tremor on activities of daily living in individuals with essential tremor. There are 12 items: speaking; feeding with a spoon; drinking from a glass; hygiene; dressing; pouring; carrying food on trays, plates or similar items; using keys; writing; working; overall disability; social impact. Each item is scored 0 (normal) to 4 (severe/severely abnormal), for a total possible score of 48, with a higher score indicated a worse impact of tremor.

Time frame: From baseline to Week 6

The CGI-C assesses the clinician's impression of how the participant's current illness has changed relative to baseline/pre-study. The clinician should use his/her total clinical experience with the individual participant and rate the participant's change in signs and reported symptoms using the scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse).

Time frame: From baseline to Week 6

The PGI-C is a written scale which will be used to solicit the participant's self-report of overall difference in PD related symptoms compared to his/her pre-study baseline. The score for each timepoint will be: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse).

Time frame: From baseline to Week 6

The SCOPA-Sleep is a validated patient-completed scale for assessing various components of sleep in individuals with PD: use of medication for sleep (2 items), nighttime sleep (5 items), global evaluation of sleep (1 item), and daytime sleepiness (6 items). A higher score represents a worse outcome.

Time frame: From baseline to Week 6

Not reported in this registry record.

A Phase 2 Study to Evaluate the Efficacy, Pharmacokinetics, Safety, and Tolerability of VIM0423 in Adults With Parkinson's Disease Tremor Insufficiently Responsive to Dopaminergic Therapy