KM-819 for Parkinson's Disease

Recruiting at 2 trial locations

Overseen By Briana Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: FAScinate Therapeutics Inc.

Must be taking: Dopaminergic drugs

Disqualifiers: Neurodegenerative disorders, Cognitive decline, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

314 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing KM-819, a new drug, to see if it can stop or slow down Parkinson's disease. It involves healthy older adults and people with Parkinson's disease. Researchers aim to find out if KM-819 is safe and can improve symptoms and daily function in these patients.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of their current Parkinson's disease medications for at least 8 weeks before joining. You won't need to stop taking your current medications.

Is KM-819 safe for humans?

KM-819 has been tested in healthy volunteers and completed phase I clinical trials, which are early studies focused on safety. These trials suggest that KM-819 is generally safe for human use. ^{1 2 3 4 5}

How is the drug KM-819 different from other Parkinson's disease treatments?

KM-819 is unique because it targets FAS-associated factor 1 (FAF1) to help reduce the buildup of a protein called α-synuclein, which is linked to Parkinson's disease. This approach aims to modify the disease itself, rather than just treating symptoms, by restoring the brain's ability to clear out harmful proteins. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy adults and those with Parkinson's disease (PD) who are stable on PD medications for at least 8 weeks. Participants should be in early to moderate stages of PD, not have other neurodegenerative disorders or significant cognitive decline, and must agree to use effective contraception.

Inclusion Criteria

My Parkinson's disease is at or below stage 4.

I have been on a stable Parkinson's medication dose for at least 8 weeks.

Body mass index (BMI) within the range 18.5 to 35 kg/m2 (inclusive)

Exclusion Criteria

Life-time history of a suicide attempt as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) for the Screening

I have experienced movement issues or involuntary movements due to levodopa.

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment Part 1a

Multiple Ascending Dose (MAD) study in healthy older adults with doses of 400 mg, 600 mg, and 800 mg of KM-819 for 7 days

1 week

Daily visits for dosing

Treatment Part 1b

Multiple Ascending Dose (MAD) study in participants with Parkinson's disease with doses of 200 mg, 400 mg, and 600 mg of KM-819 for 7 days

1 week

Daily visits for dosing

Treatment Part 2

Randomized, double-blind, multiple dose study in participants with Parkinson's disease for 730 days

104 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KM-819
• Placebo

Trial Overview The study tests KM-819's ability to slow down or stop the progression of Parkinson's disease. It compares the effects of different doses of KM-819 against a placebo in both healthy participants and those with PD.

How Is the Trial Designed?

Group I: Part 2: Cohort 2.2 Dose Y Experimental Treatment 2 Interventions

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.

Group II: Part 2: Cohort 2.1 Dose X Experimental Treatment 2 Interventions

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.

Group III: Part 1b: Cohort 1.3b Dose 600 mg Experimental Treatment 2 Interventions

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.

Group IV: Part 1b: Cohort 1.2b Dose 400 mg Experimental Treatment 2 Interventions

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.

Group V: Part 1b: Cohort 1.1b Dose 200 mg Experimental Treatment 2 Interventions

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.

Group VI: Part 1a: Cohort 1.3a Dose 800 mg Experimental Treatment 2 Interventions

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.

Group VII: Part 1a: Cohort 1.2a Dose 600 mg Experimental Treatment 2 Interventions

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.

Group VIII: Part 1a: Cohort 1.1a Dose 400 mg Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

FAScinate Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

310+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

AV-101, a pro-drug that effectively targets NMDA receptors, significantly reduced L-Dopa-induced dyskinesias (LID) in MPTP-lesioned monkeys while preserving the antiparkinsonian effects of L-Dopa.

Unlike amantadine, which has known side effects, AV-101 showed no non-motor adverse effects, suggesting it may be a safer alternative for managing LID in Parkinson's disease patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AV-101, a Pro-Drug Antagonist at the NMDA Receptor Glycine Site, Reduces L-Dopa Induced Dyskinesias in MPTP Monkeys. Bourque, M., Grégoire, L., Patel, W., et al.[2023]

In a study involving 16 patients with moderate Parkinson's disease, the NR2B-selective NMDA receptor antagonist MK-0657 did not show significant improvement in motor function compared to placebo, despite achieving the target plasma concentration.

While MK-0657 was generally well tolerated, it did lead to increases in blood pressure, indicating potential safety concerns that may limit its use in treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson's disease. Addy, C., Assaid, C., Hreniuk, D., et al.[2013]

Over the past 50 years, treatments for Parkinson's disease (PD) have improved significantly, utilizing pharmacotherapy (like L-Dopa and dopamine agonists), deep brain stimulation, and physiotherapy to manage motor symptoms effectively.

Despite ongoing research and clinical trials for new therapies, including non-dopaminergic agents and gene therapies, there are currently no disease-modifying treatments available for PD, highlighting the need for intensified research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and experimental treatments of Parkinson disease: A guide for neuroscientists. Oertel, W., Schulz, JB.[2022]

In a study of 105 Parkinson's disease patients, 16% showed significant motor improvements during placebo treatment, indicating that placebo effects can influence motor symptoms over a 6-month period.

Improvements were observed across all motor domains, particularly in bradykinesia and rigidity, suggesting that these symptoms may be more susceptible to placebo effects, and highlighting the need for longer placebo-controlled trials to fully capture these changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective changes in motor function during placebo treatment in PD. Goetz, CG., Leurgans, S., Raman, R., et al.[2022]

In a study involving 484 dyskinetic Parkinson's disease patients, it was found that placebo treatment can lead to significant improvements in dyskinesia, with 178 patients showing improvement and 37 experiencing worsening symptoms.

Factors such as older age, lower baseline Parkinsonism scores, and lower daily doses of levodopa were linked to better responses to placebo, while lower baseline dyskinesia scores were associated with worsening, suggesting that the placebo effect in dyskinesia may not be related to dopaminergic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo influences on dyskinesia in Parkinson's disease. Goetz, CG., Laska, E., Hicking, C., et al.[2018]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

A first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug for Parkinson's disease, in healthy volunteers. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacological Intervention Targeting FAF1 Restores Autophagic Flux for α-Synuclein Degradation in the Brain of a Parkinson's Disease Mouse Model. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

AV-101, a Pro-Drug Antagonist at the NMDA Receptor Glycine Site, Reduces L-Dopa Induced Dyskinesias in MPTP Monkeys. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson's disease. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Current and experimental treatments of Parkinson disease: A guide for neuroscientists. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Objective changes in motor function during placebo treatment in PD. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Placebo influences on dyskinesia in Parkinson's disease. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats. [2019]