NEU-411 for Parkinson's Disease

(NEULARK Trial)

Recruiting at 42 trial locations

Overseen By Sam Jackson, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neuron23 Inc.

Disqualifiers: Secondary parkinsonian syndromes, uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What safety data exists for NEU-411 or similar treatments in humans?

The studies reviewed do not mention NEU-411 specifically, but they do discuss similar treatments for Parkinson's disease. For example, MK-0657, a similar type of treatment, was generally well tolerated but caused increases in blood pressure. This suggests that while these treatments may be safe for some, they could have side effects like changes in blood pressure. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of this Phase 2 clinical trial is to investigate the efficacy and safety of NEU-411 in men and women aged 50-80 years with early Parkinson's Disease (PD) who have predicted elevations in the activity of the "leucine-rich repeat kinase 2" ("LRRK2" for short) pathway based on their genetic profile. A DNA test will be used to identify the "LRRK2-driven" population with predicted elevation in the LRRK2 pathway. Participants will: • Take NEU-411 or placebo every day for 52 weeks

Research Team

Fatta B Nahab, MD, FAAN FANA

Principal Investigator

Neuron23 Inc.

Eligibility Criteria

This trial is for men and women aged 50-80 with early Parkinson's Disease, who have a certain genetic profile indicating high activity in the LRRK2 pathway. They must be diagnosed with PD and have a disease severity score (mH&Y) of 1 to 2.5.

Inclusion Criteria

I am between 50 and 80 years old.

My Parkinson's is linked to the LRRK2 gene according to a specific test.

My Parkinson's disease is in the early to mid-stage.

Exclusion Criteria

I don't have any major health issues apart from my current condition.

My condition is a type of parkinsonism that's not typical Parkinson's disease.

My diabetes is not under control, with HbA1c over 8%.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NEU-411 or placebo daily for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• NEU-411

Trial Overview The study tests NEU-411 against a placebo over the course of one year to see if it's effective and safe for treating early-stage Parkinson's Disease in patients with specific genetic markers.

Participant Groups

Group I: NEU-411 Experimental Treatment 1 Intervention

Orally-administered NEU-411

Group II: Placebo Placebo Group 1 Intervention

Orally-administered matching placebo

Who Is Running the Clinical Trial?

Neuron23 Inc.

Lead Sponsor

Trials

6

Recruited

560+

Qiagen Manchester Limited

Collaborator

Roche Diagnostic Ltd.

Industry Sponsor

Trials

13

Recruited

47,800+

Findings from Research

The long-term use of the rotigotine transdermal system in early Parkinson's disease was generally well tolerated over a median exposure of approximately 5 years, with adverse events similar to those seen in shorter studies.

Despite some patients experiencing adverse events leading to withdrawal, only 24% discontinued the treatment, and the mean scores on the Unified Parkinson's Disease Rating Scale remained stable for up to 2 years, indicating sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study. Elmer, LW., Surmann, E., Boroojerdi, B., et al.[2018]

In a study involving 22 Parkinson's disease patients, a single dose of the NR2B antagonist MK-0657 (7 mg) did not significantly reduce levodopa-induced dyskinesias or improve motor symptoms, indicating it may not be an effective treatment for these issues.

Despite achieving the target plasma concentration of the drug, MK-0657 showed no meaningful impact on dyskinesia or motor function as measured by established scales, suggesting that further research is needed to explore effective treatments for levodopa-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Randomized Controlled Study to Evaluate the Effectiveness of a Single-Dose of the NR2B Selective N-Methyl-D-Aspartate Antagonist MK-0657 on Levodopa-Induced Dyskinesias and Motor Symptoms in Patients With Parkinson Disease. Herring, WJ., Assaid, C., Budd, K., 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]

The Phase I clinical trial of PF-06669571, a novel dopamine D1 receptor partial agonist, demonstrated that the drug was safe and well tolerated in 20 subjects with Parkinson's disease, with no serious safety concerns reported.

Although the primary endpoint for significant improvement in motor symptoms did not meet pre-specified criteria, a sensitivity analysis suggested potential efficacy, particularly when excluding an outlier with a very high L-DOPA dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease. Gurrell, R., Duvvuri, S., Sun, P., et al.[2018]

In a study involving 139 patients with early Parkinson's disease, the partial dopamine agonist pardoprunox significantly improved motor function, as measured by the Unified PD Rating Scale (UPDRS)-Motor score, compared to placebo, with a mean improvement of -7.3 points versus -3.0 points (P = 0.0001).

The study also found that 50.7% of patients treated with pardoprunox experienced a greater than 30% reduction in UPDRS-Motor score, indicating a strong response rate, although side effects like nausea were reported in 47.1% of treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease. Bronzova, J., Sampaio, C., Hauser, RA., et al.[2012]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study. [2018]

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

A Phase Ib Randomized Controlled Study to Evaluate the Effectiveness of a Single-Dose of the NR2B Selective N-Methyl-D-Aspartate Antagonist MK-0657 on Levodopa-Induced Dyskinesias and Motor Symptoms in Patients With Parkinson Disease. [2018]

3. 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]

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

A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease. [2018]

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

Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease. [2012]