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

NCT05670782 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: FASCP-819-K103
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Parkinson Disease

Keywords

Inhibition of FAF1(Fas (TNFRSF6)-associated factor 1); Multiple Ascending Dose (MAD); Neuroprotection; Alpha-synuclein inhibition; KM-819

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (28)

• 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)

  Day 1

• Part 1a and 1b: AUC from pre-dose (time zero) to 24 hours post-dose [AUC(0-24)]

  Day 1

• Part 1a and 1b: Maximum concentration (Cmax)

  Day 1

• Part 1a and 1b: Time to achieve Cmax (tmax)

  Day 1

• Part 1a and 1b: Minimum concentration (Cmin)

  Day 1

Other Outcomes (1)

• Digital biomarkers using the Parkinson's Disease Digital Biomarker Solutions from Roche Molecular Solutions.

  From screening (Day -42 to -2) to 2 years

Study Arms (8)

Part 1a: Cohort 1.1a Dose 400 mg

EXPERIMENTAL

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; Drug: Placebo

Part 1a: Cohort 1.2a Dose 600 mg

EXPERIMENTAL

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; Drug: Placebo

Part 1a: Cohort 1.3a Dose 800 mg

EXPERIMENTAL

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; Drug: Placebo

Part 1b: Cohort 1.1b Dose 200 mg

EXPERIMENTAL

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; Drug: Placebo

Part 1b: Cohort 1.2b Dose 400 mg

EXPERIMENTAL

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; Drug: Placebo

Part 1b: Cohort 1.3b Dose 600 mg

EXPERIMENTAL

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; Drug: Placebo

Part 2: Cohort 2.1 Dose X

EXPERIMENTAL

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; Drug: Placebo

Part 2: Cohort 2.2 Dose Y

EXPERIMENTAL

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; Drug: Placebo

Interventions

KM-819 DRUG

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

Part 1a: Cohort 1.1a Dose 400 mg; Part 1a: Cohort 1.2a Dose 600 mg; Part 1a: Cohort 1.3a Dose 800 mg; Part 1b: Cohort 1.1b Dose 200 mg; Part 1b: Cohort 1.2b Dose 400 mg; Part 1b: Cohort 1.3b Dose 600 mg; Part 2: Cohort 2.1 Dose X; Part 2: Cohort 2.2 Dose Y

Placebo DRUG

Participants will receive matching placebo once-daily

Part 1a: Cohort 1.1a Dose 400 mg; Part 1a: Cohort 1.2a Dose 600 mg; Part 1a: Cohort 1.3a Dose 800 mg; Part 1b: Cohort 1.1b Dose 200 mg; Part 1b: Cohort 1.2b Dose 400 mg; Part 1b: Cohort 1.3b Dose 600 mg; Part 2: Cohort 2.1 Dose X; Part 2: Cohort 2.2 Dose Y

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• FAScinate Therapeutics Inc.: lead
• Parexel: collaborator

Study Sites (3)

Parexel Early Phase Clinical Unit

Glendale, California, 91206, United States

Location

University California San Diego Medical Center

San Diego, California, 92103, United States

Location

Quest Research Institute, Rose Cancer Center

Royal Oak, Michigan, 48073, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

KM-819

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-Blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 4, 2023
• Study Start: July 19, 2022
• Primary Completion: October 30, 2025
• Study Completion: November 13, 2025
• Last Updated: March 5, 2025

Record last verified: 2024-06

Locations

US (3)