VTX3232 for Parkinson's Disease

Overseen By Ventyx Clinical Trial Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zomagen Biosciences, Ltd

Disqualifiers: Other Parkinsonian syndrome, CNS disease, 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

Duration: 4 weeks

11 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications. However, if you are on symptomatic Parkinson's Disease therapies, your treatment must be stable. It's best to contact the Medical Monitor with any questions about your current medications.

What data supports the idea that VTX3232 for Parkinson's Disease (also known as: VTX3232) is an effective treatment?

The available research does not provide specific data on VTX3232 for Parkinson's Disease. However, it discusses other drugs like ropinirole and pramipexole, which are used for Parkinson's Disease. These studies show that these drugs can help manage symptoms in advanced stages of the disease. For example, ropinirole prolonged release was compared to its immediate release form, and pramipexole was tested for its safety and effectiveness. Another drug, S32504, showed promise in animal studies by improving movement without causing unwanted side effects. While these studies do not mention VTX3232, they highlight the potential of similar drugs in treating Parkinson's Disease. ^{1 2 3 4 5}

What safety data is available for VTX3232 in treating Parkinson's Disease?

The provided research does not mention VTX3232 specifically. However, it includes studies on pramipexole, a dopamine agonist used in Parkinson's Disease treatment. Pramipexole has been evaluated for safety and efficacy in several studies, showing it is generally well-tolerated with common side effects like dyskinesias, orthostatic hypotension, dizziness, insomnia, and hallucinations. Long-term studies indicate it is safe for up to 4 years, with continued efficacy for 3 years before a gradual return to baseline motor states. ^{4 6 7 8 9}

Is the drug VTX3232 a promising treatment for Parkinson's Disease?

Yes, VTX3232, also known as S32504, is a promising drug for Parkinson's Disease. It shows strong potential in improving movement and reducing symptoms without causing significant side effects. It works by targeting specific brain receptors, which helps protect brain cells and improve motor function. ^{1 7 10 11 12}

What is the purpose of this trial?

This is a study to understand if taking VTX3232 is safe in participants diagnosed with early stage idiopathic Parkinson's Disease (PD). Approximately 10 patients will take VTX3232 Dose A. The study consists of a 30-day Screening Period (to see if a participant qualifies for the study), a 7-day Pre-Baseline Period, a 28-day Open Label Treatment period (a participant receives active Dose A), and a 14-day Follow-Up Period.

Research Team

Snehal Naik, PhD

Principal Investigator

Zomagen Biosciences Ltd.

Eligibility Criteria

This clinical trial is for about 10 people with early stage idiopathic Parkinson's Disease. Participants must pass a screening to qualify and will be involved in the study for around 79 days, including treatment and follow-up periods.

Inclusion Criteria

I was diagnosed with Parkinson's Disease within the last 5 years.

I am between 40 and 80 years old, with a healthy weight for my height.

My Parkinson's symptoms are mild, scoring 2 or less on a specific scale.

Exclusion Criteria

My condition is a type of Parkinsonian syndrome, not classic Parkinson's Disease.

I have had brain surgery in the past.

I do not have Parkinson's, but I have a significant brain condition or a history of serious head injuries or seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Pre-Baseline

Participants undergo a pre-baseline period before starting treatment

1 week

Treatment

Participants receive the study medication VTX3232 Dose A

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• VTX3232

Trial Overview The trial is testing the safety of a new medication called VTX3232 in patients with Parkinson's Disease. It includes several phases: screening, pre-baseline, a treatment period where participants receive the drug, and follow-up.

Participant Groups

Group I: VTX3232 Dose A Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Zomagen Biosciences, Ltd

Lead Sponsor

Trials

2

Recruited

20+

Zomagen Biosciences Ltd.

Lead Sponsor

Trials

4

Recruited

210+

Findings from Research

The novel D3/D2 receptor agonist S32504 enhances locomotor activity and shows significant antiparkinsonian effects in a nonhuman primate model of Parkinson's disease, without causing dyskinesia, which is a common side effect of L-dopa treatment.

S32504's effects are primarily mediated through D2 receptor activation, and it demonstrates rapid and durable antiparkinsonian properties, becoming effective within 5 minutes of administration and lasting over 4 hours, making it a promising alternative for newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiparkinsonian effects of the novel D3/D2 dopamine receptor agonist, S32504, in MPTP-lesioned marmosets: Mediation by D2, not D3, dopamine receptors. Hill, MP., Ravenscroft, P., McGuire, SG., et al.[2013]

In a 24-week study involving 350 patients with advanced Parkinson's disease, adjunctive ropinirole prolonged release (PR) significantly improved symptom control by increasing the likelihood of patients achieving a ≥ 20% reduction in 'off' time compared to immediate release (IR) ropinirole.

Both PR and IR had similar safety profiles, with 72% of patients in the PR group and 61% in the IR group reporting adverse events, indicating that PR is a well-tolerated option for managing Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease. Stocchi, F., Giorgi, L., Hunter, B., et al.[2022]

CVT-301 significantly increased the likelihood of patients with Parkinson's disease achieving an 'ON state' compared to placebo, with an odds ratio of 2.68, indicating its efficacy in managing motor fluctuations.

The treatment also improved motor function as measured by the Unified Parkinson Disease Rating Scale, with a standardized mean difference of 3.83, although it was associated with some adverse effects like respiratory symptoms and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Glenardi, G., Handayani, T., Barus, J., et al.[2023]

In a phase II study involving 78 advanced Parkinson's disease patients, pramipexole significantly improved motor function and daily activities, with a 37.3% reduction in UPDRS total scores compared to 12.2% for placebo (p<0.001).

Pramipexole was well tolerated, with no unexpected safety issues, although some patients experienced fatigue, dyskinesia, and vivid dreams; it also reduced 'off' periods by 12%, leading to 1.7 more hours of 'on' time per day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study. Pinter, MM., Pogarell, O., Oertel, WH.[2019]

In a Phase IV study involving subjects with advanced Parkinson's disease, ropinirole prolonged release (PR) at a dose of 16 mg significantly reduced total awake 'Off-time' compared to placebo, indicating its efficacy in managing symptoms.

The study found that ropinirole PR improved motor scores on the Unified Parkinson's Disease Rating Scale across all doses tested, with a similar incidence of adverse events between treatment groups, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, fixed-dose, dose-response study of ropinirole prolonged release in advanced Parkinson's disease. Zesiewicz, TA., Chriscoe, S., Jimenez, T., et al.[2018]

Pramipexole (PPX) was evaluated for its efficacy and safety as an additional treatment for advanced Parkinson's disease in patients already taking levodopa, compared to a placebo.

The study also included a bromocriptine (BR) group to assess whether PPX is at least as effective as BR, which is considered a standard treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease. Mizuno, Y., Yanagisawa, N., Kuno, S., et al.[2018]

The novel compound S32504, a preferential D(3) receptor agonist, shows superior potency in restoring motor function in rodent and primate models compared to other D(3) agonists like pramipexole and ropinirole.

S32504 provides robust neuroprotection against cell death induced by neurotoxins in both in vitro and in vivo models, significantly outperforming ropinirole, which showed neurotoxic effects at high doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole. Joyce, JN., Presgraves, S., Renish, L., et al.[2019]

In a rat model of Parkinson's disease, pramipexole effectively reduced motor disturbances (akinesia) without compromising motor function, demonstrating its efficacy in treating symptoms of the disease.

Co-administration of mirtazapine with pramipexole successfully reduced impulsive behaviors (risk-taking) without affecting the motor benefits, suggesting a potential adjunct treatment strategy for patients experiencing compulsive behaviors while on dopamine agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease. Holtz, NA., Tedford, SE., Persons, AL., et al.[2018]

In a long-term study of 306 patients with advanced Parkinson's disease, pramipexole was well tolerated and showed continued efficacy for up to 3 years, with significant improvements in motor function as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

Despite the initial benefits, patients began to return to baseline motor function after 3 years, indicating potential disease progression, although improvements in tremor during 'on' periods were maintained throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term safety and efficacy of pramipexole in advanced Parkinson's disease. Weiner, WJ., Factor, SA., Jankovic, J., et al.[2019]

S32504, a novel dopamine D(3)/D(2) receptor agonist, demonstrated stronger antiparkinsonian effects than the clinically used ropinirole in various animal models, including rats and marmosets, indicating its potential as a more effective treatment for Parkinson's disease.

The mechanism of action for S32504 involves both D(2) and D(3) receptor activation, with D(2) receptors being essential for motor effects and D(3) receptors contributing to neuroprotection, suggesting a dual benefit in treating Parkinson's symptoms and protecting dopaminergic neurons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: II. Actions in rodent, primate, and cellular models of antiparkinsonian activity in comparison to ropinirole. Millan, MJ., Di Cara, B., Hill, M., et al.[2013]

Early administration of PT320 significantly reduced L-DOPA-induced dyskinetic behaviors in a progressive Parkinson's disease mouse model, particularly improving abnormal movements without affecting locomotor hyperactivity.

PT320 treatment enhanced dopamine release in the striatum of both L-DOPA-naïve and L-DOPA-primed mice, suggesting its potential mechanism in mitigating dyskinesia is linked to improving dopaminergic transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease. Kuo, TT., Chen, YH., Wang, V., et al.[2023]

Pimavanserin, a selective 5-HT2A receptor inverse agonist, has shown significant efficacy in treating Parkinson's disease psychosis (PDP) in a Phase III clinical trial, improving symptoms without worsening motor function, which is a common concern with other atypical antipsychotics.

The drug demonstrated good safety and tolerability over long-term use, making it a promising treatment option for PDP, especially since it does not carry the same risks associated with other antipsychotic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis. Hacksell, U., Burstein, ES., McFarland, K., et al.[2022]

References

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

Antiparkinsonian effects of the novel D3/D2 dopamine receptor agonist, S32504, in MPTP-lesioned marmosets: Mediation by D2, not D3, dopamine receptors. [2013]

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

PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease. [2022]

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

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. [2023]

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

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study. [2019]

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

A randomized, fixed-dose, dose-response study of ropinirole prolonged release in advanced Parkinson's disease. [2018]

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

Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease. [2018]

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

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease. [2018]

9. England pubmed.ncbi.nlm.nih.gov

The long-term safety and efficacy of pramipexole in advanced Parkinson's disease. [2019]

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

S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: II. Actions in rodent, primate, and cellular models of antiparkinsonian activity in comparison to ropinirole. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease. [2023]

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

On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis. [2022]