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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: KM-819; Drug: Placebo

Detailed Description

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
• Enrollment (Estimated): 330
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JAE MOON LEE; Phone Number: (858)630-8540; Email: jmlee@fascinatetherapeutics.com
• Study Contact Backup: Name: Briana Lee; Phone Number: (858)630-8543; Email: bblee@fascinatetherapeutics.com

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • PAREXEL Early Phase Clinical Unit
    • San Diego, California, United States, 92103
      • Not yet recruiting
      • University California San Diego Medical Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Enrolling by invitation
      • Quest Research Institute, Rose Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a: Cohort 1.1a Dose 400 mg; Healthy older adult participants will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 1a: Cohort 1.2a Dose 600 mg; Healthy older adult participants will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 1a: Cohort 1.3a Dose 800 mg; Healthy older adult participants will receive oral 800 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 1b: Cohort 1.1b Dose 200 mg; Participants with Parkinson's disease will receive oral 200 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 1b: Cohort 1.2b Dose 400 mg; Participants with Parkinson's disease will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 1b: Cohort 1.3b Dose 600 mg; Participants with Parkinson's disease will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 2: Cohort 2.1 Dose X; Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily
Experimental: Part 2: Cohort 2.2 Dose Y; Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.	Drug: KM-819; Participants will receive oral doses of KM-819 once-daily; Drug: Placebo; Participants will receive matching placebo once-daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	From screening (Day -42 to -2) to Day 730

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: AUC from pre-dose (time zero) to 24 hours post-dose [AUC(0-24)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Maximum concentration (Cmax)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Time to achieve Cmax (tmax)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Minimum concentration (Cmin)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: AUC normalized to dose administered (AUC_D)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Cmax normalized to dose administered (Cmax_D)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: AUC from pre-dose (time zero) extrapolated to time infinity [AUC(0-inf)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Apparent terminal elimination half-life (t½)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Terminal elimination rate constant (λz)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Percentage of AUCinf that is extrapolated beyond the time of the last quantifiable concentration [%AUC (extrap)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: Apparent oral clearance (CL/F)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: AUC(0-t) at steady state (Vz/F)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 1
Part 1a and 1b: AUC(0-t) at steady state [AUC(0-t_ss)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: AUCtau at steady state [AUC(tau_ss)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Cmax at steady state (Cmax,ss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: tmax at steady state (tmax,ss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Ctrough at steady state (Ctrough_ss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Minimum concentration at steady state (Cmin,ss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Average observed concentration at steady state (Cav,ss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Accumulation ratio calculated using AUC [Rac (AUC)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Accumulation ratio calculated using Cmax [Rac (Cmax)]	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Apparent oral clearance at steady state (CL/Fss)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: AUC normalized to dose administered at steady state (AUCss_D)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Cmax_ss normalized to dose administered (Cmaxss_D)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma	Day 7
Part 1a and 1b: Fraction of dose excreted in urine (Fe)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine	Day 7
Part 1a and 1b: Renal clearance (CLR)	To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine	Day 7
Part 2: Sparse plasma PK blood sampling for population PK analysis	Sparse plasma population PK sampling will be collected, and population PK modeling will be used to characterize the PK of KM-819 in participants with Parkinson's disease.	Day 1, Day 7, Day 30 and Day 180

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digital biomarkers using the Parkinson's Disease Digital Biomarker Solutions from Roche Molecular Solutions.	Measurements of active and passive monitoring of Parkinson's disease symptoms utilizing smartphone based devices and software	From screening (Day -42 to -2) to 2 years

Collaborators and Investigators

• Sponsor: FAScinate Therapeutics Inc.
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2022
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): November 13, 2025

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Neuroprotection; Multiple Ascending Dose (MAD); Inhibition of FAF1(Fas (TNFRSF6)-associated factor 1); Alpha-synuclein inhibition; KM-819
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: FASCP-819-K103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual Identifiable personal information will not be shared. All individuals will be coded.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No