A Study to Evaluate Safety and Efficacy of KM-819 in Healthy Adults and Participants with Parkinson's Disease

A Phase 2 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of KM-819 in Healthy Older Adults and Participants with Parkinson's Disease

The goal of this study is to test KM-819 in halting or slowing the progression of Parkinson's disease.

The study evaluates the safety and tolerability of multiple ascending doses of KM-819 in healthy older adults and participants with Parkinson's disease.

The overall study will consist of three parts (Part 1a, Part 1b and Part 2).

Part 1 of this study will evaluate the safety, tolerability and plasma PK of multiple ascending doses (MAD) of KM-819 in healthy older adults (Part 1a) and participants with Parkinson's disease (Part 1b).

• Part 1a is a randomized, double-blind, Multiple Ascending Dose (MAD) study in healthy older adults that will include 3 cohorts.
• Part 1b is a randomized, double-blind, MAD study in participants with Parkinson's disease that will include 3 cohorts.

Part 2 of the study is a randomized, double-blind, multiple dose study in participants with Parkinson's disease that will include 2 cohorts. It is designed to test the safety, tolerability, plasma PK and pharmacodynamic effects of KM-819 in participants with Parkinson's disease. The study will also assess the degree to which those treated with KM-819 will experience gains in overall daily function within the context of improved Parkinson's disease motor and non-motor symptoms in comparison to placebo. Participants will be randomized to receive KM-819 or matching placebo at doses to be determined based on the findings from Part 1 in a 2:1 ratio.

Inclusion Criteria:

• Participant is a healthy volunteer or has a clinical diagnosis of idiopathic Parkinson's disease.
• Participant is on a stable dose of medications to treat Parkinson's disease at least 8 weeks prior to randomization
• Presence of idiopathic Parkinson's disease Hoehn and Yahr Stage ≤ 4
• History or current use of dopamine/dopaminergic drugs, levodopa with decarboxylase inhibitor or dopaminergic agonists, with a stable dosage for at least 30 days prior to Screening
• Body mass index (BMI) within the range 18.5 to 35 kg/m2 (inclusive)
• A male participant must not have a pregnant or breastfeeding partner and must agree to use a highly effective contraception method starting from Screening and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding

Exclusion Criteria:

• Diagnosis of neurodegenerative disorder other than idiopathic Parkinson's disease resulting in dementia or atypical parkinsonism
• Life-time history of a suicide attempt as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) for the Screening
• Evidence of cognitive decline defined by the Montreal Cognitive Assessment (MoCA) score ≤25 for healthy normal population (Part 1a) and ≤21 for the patient population (Part 1b and Part 2)
• History of levodopa-induced motor fluctuations or dyskinesia
• Prior surgical treatment for Parkinson's disease
• Clinically significant brain abnormalities on or contraindication to a structural magnetic resonance imaging (MRI)
• Significant respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, pancreatic, musculoskeletal, genitourinary, immunological or dermatological disorders.