KM-819 for Parkinson's Disease

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, KM-819, to determine if it can slow or stop the progression of Parkinson’s disease. Researchers aim to assess the drug's safety and tolerability at various doses. The trial consists of two main parts: one for healthy older adults and another for individuals with Parkinson’s. It suits those diagnosed with Parkinson's who are on a stable treatment plan. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KM-819 has been safe in earlier studies. In one study, researchers tested three different doses of KM-819 on healthy adults and found them to be safe, with no serious side effects reported compared to those who took a placebo, a substance with no active medicine. Another study supported these findings, demonstrating that KM-819 is well-tolerated in people. These results suggest that KM-819 could be a safe option for treating Parkinson's disease, as it has been safely tested in healthy individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Researchers are excited about KM-819 for Parkinson's disease because it offers a fresh approach compared to current treatments like Levodopa or dopamine agonists. Unlike these standard treatments, which primarily focus on replacing or mimicking dopamine, KM-819 targets a different aspect of the disease by potentially modifying the underlying disease process itself. This could mean slowing down the progression of Parkinson's, rather than just managing symptoms. Additionally, KM-819 is administered orally and has the potential for flexible dosing, making it a convenient option for patients.

What evidence suggests that KM-819 might be an effective treatment for Parkinson's disease?

Research shows that KM-819 blocks a process leading to cell death, which is linked to Parkinson's disease. In lab studies, KM-819 has shown potential in slowing the disease's progression. Previous trials found that KM-819 was safe at different doses in healthy adults, encouraging its use in Parkinson's patients. In this trial, participants will receive various doses of KM-819 or a placebo. In Parkinson's, a protein called FAF1 is overly active in certain brain cells, and KM-819 targets this protein. By reducing FAF1 activity, KM-819 aims to slow or stop the disease's progression. These findings suggest that KM-819 could effectively treat Parkinson's. ^{1 2 3 4 6}

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

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05695378

Trial to Evaluate the Efficacy and Safety of KM-819 ... This is a randomized, double-blind, placebo-controlled phase II trial. This trial will be performed in two part: Main study and Ancillary study.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6445238/

A first-in-human study to investigate the safety, tolerability ... KM-819 inhibits Parkinson's disease progression by inhibiting the Fas-mediated cell death pathway.9,10 According to an in vitro study, KM-819 was found to ...

3. cndlifesciences.com cndlifesciences.com/fascinate-therapeutics-parkinsons/

KM-819 for the Treatment of Parkinson's Disease ... In part 1a of the Phase 2 trial, three dosage strengths of KM-819 demonstrated a favorable safety profile compared to placebo in healthy adults.

4. neurologylive.com neurologylive.com/view/parkinson-disease-agent-km-819-demonstrates-safe-profile-phase-2-study

Parkinson Disease Agent KM-819 Demonstrates Safe ... When administered to the elderly population, KM-819 plasma exposure increased by 102% after a 200 mg once daily dosing for 7 days. The therapy ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10934217/

Rat Pharmacokinetics and In Vitro Metabolite Identification ... In patients with Parkinson's disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30992659/

A first-in-human study to investigate the safety, tolerability, ... A first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug ...