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

Phase 2Active Not RecruitingNCT05670782

FAScinate Therapeutics Inc.314 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

314

Conditions

Parkinson Disease

Interventions

KM-819DRUG

Participants will receive oral doses of KM-819 once-daily

PlaceboDRUG

Participants will receive matching placebo once-daily

Eligibility

Sex: ALLMin age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

Parexel Early Phase Clinical Unit

Glendale, California, United States

University California San Diego Medical Center

San Diego, California, United States

Quest Research Institute, Rose Cancer Center

Royal Oak, Michigan, United States

Outcomes

Primary Outcomes

Part 1a,1b and 2: Number of participants with adverse events and serious adverse events

To evaluate the safety and tolerability of multiple ascending doses of KM-819

Time frame: Part 1a and Part 1b: From screening (Day -42 to -3) up to 7 days and Part 2: From screening (Day -42 to -2) to 730 days

Part 2: Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II: Activities of Daily Living (ADL) Score at Day 730

Activities of Daily living (ADL) will be assessed via MDS-UPDRS score. MDS-UPDRS Part II is a self-administered questionnaire that assesses the motor experience of daily living in participants with Parkinson's disease. Score: 0: Normal, 1: Slight, 2: Mild, 3: Moderate, 4: Severe. Higher the score, the more severe the condition or symptom

Time frame: From screening (Day -42 to -2) to Day 730

Secondary Outcomes

Part 1a and 1b: Area under the concentration-time curve (AUC) from pre-dose (time zero) to the time of the last quantifiable concentration AUC(0-t)