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

Primary Purpose

Parkinson Disease

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

KM-819

Placebo

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Inhibition of FAF1(Fas (TNFRSF6)-associated factor 1), Multiple Ascending Dose (MAD), Neuroprotection, Alpha-synuclein inhibition, KM-819

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Parexel Early Phase Clinical UnitRecruiting
University California San Diego Medical Center
Quest Research Institute, Rose Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

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

Arm Description

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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 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

Secondary Outcome Measures

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

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

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

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

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

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

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

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

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

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

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

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

Part 1a and 1b: Terminal elimination rate constant (λz)

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

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

Part 1a and 1b: Apparent oral clearance (CL/F)

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Part 1a and 1b: Renal clearance (CLR)

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine

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.

Full Information

NCT ID

NCT05670782

First Posted

December 21, 2022

Last Updated

August 31, 2023

Sponsor

FAScinate Therapeutics Inc.

Collaborators

Parexel

1. Study Identification

Unique Protocol Identification Number

NCT05670782

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 19, 2022 (Actual)

Primary Completion Date

October 30, 2025 (Anticipated)

Study Completion Date

November 13, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

FAScinate Therapeutics Inc.

Collaborators

Parexel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Masking Description

Double-Blinded

Allocation

Randomized

Enrollment

330 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1a: Cohort 1.1a Dose 400 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 1a: Cohort 1.2a Dose 600 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 1a: Cohort 1.3a Dose 800 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 1b: Cohort 1.1b Dose 200 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 1b: Cohort 1.2b Dose 400 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 1b: Cohort 1.3b Dose 600 mg

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Cohort 2.1 Dose X

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Cohort 2.2 Dose Y

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

KM-819

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive matching placebo once-daily

Primary Outcome Measure Information:

Title

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

Description

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

Title

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

Description

Time Frame

From screening (Day -42 to -2) to Day 730

Secondary Outcome Measure Information:

Title

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)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

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

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

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

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

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

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

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

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: AUC normalized to dose administered (AUC_D)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: Cmax normalized to dose administered (Cmax_D)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: AUC from pre-dose (time zero) extrapolated to time infinity [AUC(0-inf)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: Apparent terminal elimination half-life (t½)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: Terminal elimination rate constant (λz)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: Percentage of AUCinf that is extrapolated beyond the time of the last quantifiable concentration [%AUC (extrap)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: Apparent oral clearance (CL/F)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: AUC(0-t) at steady state (Vz/F)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 1

Title

Part 1a and 1b: AUC(0-t) at steady state [AUC(0-t_ss)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: AUCtau at steady state [AUC(tau_ss)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Cmax at steady state (Cmax,ss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: tmax at steady state (tmax,ss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Ctrough at steady state (Ctrough_ss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Minimum concentration at steady state (Cmin,ss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Average observed concentration at steady state (Cav,ss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Accumulation ratio calculated using AUC [Rac (AUC)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Accumulation ratio calculated using Cmax [Rac (Cmax)]

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Apparent oral clearance at steady state (CL/Fss)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: AUC normalized to dose administered at steady state (AUCss_D)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Cmax_ss normalized to dose administered (Cmaxss_D)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma

Time Frame

Day 7

Title

Part 1a and 1b: Fraction of dose excreted in urine (Fe)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine

Time Frame

Day 7

Title

Part 1a and 1b: Renal clearance (CLR)

Description

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine

Time Frame

Day 7

Title

Part 2: Sparse plasma PK blood sampling for population PK analysis

Description

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.

Time Frame

Day 1, Day 7, Day 30 and Day 180

Other Pre-specified Outcome Measures:

Title

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

Description

Measurements of active and passive monitoring of Parkinson's disease symptoms utilizing smartphone based devices and software

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

JAE MOON LEE

Phone

(858)630-8540

jmlee@fascinatetherapeutics.com

First Name & Middle Initial & Last Name or Official Title & Degree

Briana Lee

Phone

(858)630-8543

bblee@fascinatetherapeutics.com

Facility Information:

Facility Name

Parexel Early Phase Clinical Unit

City

Glendale

State/Province

California

ZIP/Postal Code

91206

Country

United States

Individual Site Status

Recruiting

Facility Name

University California San Diego Medical Center

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Individual Site Status

Not yet recruiting

Facility Name

Quest Research Institute, Rose Cancer Center

City

Royal Oak

State/Province

Michigan

ZIP/Postal Code

48073

Country

United States

Individual Site Status

Enrolling by invitation

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Individual Identifiable personal information will not be shared. All individuals will be coded.

Learn more about this trial

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

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