Clinical trial NCT05670782: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Inhibition of FAF1(Fas (TNFRSF6)-associated factor 1)
Multiple Ascending Dose (MAD)
Neuroprotection
Alpha-synuclein inhibition
KM-819
Lead sponsor: Kainos Medicine Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-01-04
Enrollment: 314
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Part 1a,1b and 2: Number of participants with adverse events and serious adverse events
timeFrame: 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
measure: 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
timeFrame: From screening (Day -42 to -2) to Day 730
Secondary outcomes:
measure: 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)
timeFrame: Day 1
measure: Part 1a and 1b: AUC from pre-dose (time zero) to 24 hours post-dose [AUC(0-24)]
timeFrame: Day 1
measure: Part 1a and 1b: Maximum concentration (Cmax)
timeFrame: Day 1
measure: Part 1a and 1b: Time to achieve Cmax (tmax)
timeFrame: Day 1
measure: Part 1a and 1b: Minimum concentration (Cmin)
timeFrame: Day 1
measure: Part 1a and 1b: AUC normalized to dose administered (AUC_D)
timeFrame: Day 1
measure: Part 1a and 1b: Cmax normalized to dose administered (Cmax_D)
timeFrame: Day 1
measure: Part 1a and 1b: AUC from pre-dose (time zero) extrapolated to time infinity [AUC(0-inf)]
timeFrame: Day 1
measure: Part 1a and 1b: Apparent terminal elimination half-life (t½)
timeFrame: Day 1
measure: Part 1a and 1b: Terminal elimination rate constant (λz)
timeFrame: Day 1
measure: Part 1a and 1b: Percentage of AUCinf that is extrapolated beyond the time of the last quantifiable concentration [%AUC (extrap)]
timeFrame: Day 1
measure: Part 1a and 1b: Apparent oral clearance (CL/F)
timeFrame: Day 1
measure: Part 1a and 1b: AUC(0-t) at steady state (Vz/F)
timeFrame: Day 1
measure: Part 1a and 1b: AUC(0-t) at steady state [AUC(0-t_ss)]
timeFrame: Day 7
measure: Part 1a and 1b: AUCtau at steady state [AUC(tau_ss)]
timeFrame: Day 7
measure: Part 1a and 1b: Cmax at steady state (Cmax,ss)
timeFrame: Day 7
measure: Part 1a and 1b: tmax at steady state (tmax,ss)
timeFrame: Day 7
measure: Part 1a and 1b: Ctrough at steady state (Ctrough_ss)
timeFrame: Day 7
measure: Part 1a and 1b: Minimum concentration at steady state (Cmin,ss)
timeFrame: Day 7
measure: Part 1a and 1b: Average observed concentration at steady state (Cav,ss)
timeFrame: Day 7
measure: Part 1a and 1b: Accumulation ratio calculated using AUC [Rac (AUC)]
timeFrame: Day 7
measure: Part 1a and 1b: Accumulation ratio calculated using Cmax [Rac (Cmax)]
timeFrame: Day 7
measure: Part 1a and 1b: Apparent oral clearance at steady state (CL/Fss)
timeFrame: Day 7
measure: Part 1a and 1b: AUC normalized to dose administered at steady state (AUCss_D)
timeFrame: Day 7
measure: Part 1a and 1b: Cmax_ss normalized to dose administered (Cmaxss_D)
timeFrame: Day 7
measure: Part 1a and 1b: Fraction of dose excreted in urine (Fe)
timeFrame: Day 7
measure: Part 1a and 1b: Renal clearance (CLR)
timeFrame: Day 7
measure: Part 2: Sparse plasma PK blood sampling for population PK analysis
timeFrame: Day 1, Day 7, Day 30 and Day 180
Other outcomes:
measure: Digital biomarkers using the Parkinson's Disease Digital Biomarker Solutions from Roche Molecular Solutions.
timeFrame: From screening (Day -42 to -2) to 2 years
Locations:
city: Glendale
country: United States
facility: Parexel Early Phase Clinical Unit
state: California
city: San Diego
country: United States
facility: University California San Diego Medical Center
state: California
city: Royal Oak
country: United States
facility: Quest Research Institute, Rose Cancer Center
state: Michigan
Study officials:
References: