a study to evaluate safety and efficacy of km-819 in healthy adults and participants with parkinson's disease

Conditions: Parkinson Disease

Summary: 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.

Eligibility criteria:
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.

Keywords: inhibition of faf1(fas (tnfrsf6)-associated factor 1) multiple ascending dose (mad) neuroprotection alpha-synuclein inhibition km-819