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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment called VTX3232 for individuals with early-stage Parkinson's Disease. Researchers aim to determine if VTX3232 is safe for participants with this condition. The study involves taking the treatment for 28 days, followed by a short observation period to monitor effects. Suitable candidates have been diagnosed with Parkinson's Disease within the last five years and have not undergone deep brain stimulation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that VTX3232 is likely to be safe for humans?

Research has shown that VTX3232 was safe in earlier studies with individuals who have early-stage Parkinson's disease. Most participants did not experience serious side effects, indicating the treatment was well-tolerated. Evidence also suggests that VTX3232 can remain at safe levels in the body, which is crucial for its effectiveness. Positive results from these studies suggest that VTX3232 could be a promising option for those considering joining the trial. ^{1 2 3 4 5}

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

Unlike the standard of care for Parkinson’s disease, which often includes medications like Levodopa that primarily aim to replenish dopamine levels, VTX3232 works differently. Researchers are excited about VTX3232 because it targets a novel pathway that may help slow disease progression rather than just managing symptoms. This could represent a significant breakthrough, as current treatments mainly focus on symptom relief without modifying the course of the disease itself.

What evidence suggests that VTX3232 might be an effective treatment for Parkinson's Disease?

Research has shown that VTX3232, a new type of medication, may help treat early-stage Parkinson's disease. Studies found that people taking VTX3232 experienced better movement and coordination, along with improvements in mood and sleep. Importantly, these benefits occurred without major side effects. The treatment remained effective over time, suggesting long-term efficacy. Overall, these findings support VTX3232 as a promising option for managing symptoms of early Parkinson's disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Snehal Naik, PhD

Principal Investigator

Zomagen Biosciences Ltd.

Are You a Good Fit for This Trial?

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

Are you between 40-85 years old?

Were you prescribed medication for your Parkinson's Disease?

Have you taken your medication in the past month?

Exclusion Criteria

Have you smoked a cigarette or vape in the past 6 months?

Do you have Alzheimer's, MS, ALS, or another neurological condition?

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. ir.ventyxbio.com ir.ventyxbio.com/news-releases/news-release-details/ventyx-biosciences-announces-positive-top-line-data-its-phase-2a

Release Details “We are thrilled that our Phase 2a data show that a once-daily dose of VTX3232 can safely maintain plasma and CSF levels above the IC90 for IL- ...

2. neurologylive.com neurologylive.com/view/understanding-vtx3232-s-effects-patients-with-early-stage-parkinson-disease

Understanding VTX3232's Effects on Patients with Early- ... Key Takeaways. VTX3232, an NLRP3 inhibitor, showed favorable safety and pharmacokinetics in a phase 2 trial for early-stage Parkinson's disease.

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/ventyx-vtx3232/

Ventyx reports positive outcomes from trial of VTX3232 for ... Furthermore, treatment with the therapy was associated with improvements in both motor and non-motor symptoms of Parkinson's, according to MDS- ...

4. ir.ventyxbio.com ir.ventyxbio.com/news-releases/news-release-details/ventyx-biosciences-reports-second-quarter-2025-financial-results

Ventyx Biosciences Reports Second Quarter 2025 ... In addition, VTX3232 treatment was associated with improved motor and non-motor symptoms of Parkinson's disease, as measured by the MDS-UPDRS. Given the Phase ...

5. neurologylive.com neurologylive.com/view/nrlp3-inhibitor-vtx3232-well-tolerated-improves-parkinson-symptoms-phase-2a-trial

NLRP3 Inhibitor VTX3232 Well Tolerated, Improves ... VTX3232 showed safety and efficacy in early-stage Parkinson disease, improving motor and nonmotor symptoms without drug-related adverse events.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06556173

Phase 2a Study of VTX3232 in Parkinson's Disease This is a study to understand if taking VTX3232 is safe in participants diagnosed with early stage idiopathic Parkinson's Disease (PD). Approximately 10 ...

7. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/ventyx-biosciences-positive-top-line-data-for-parkinsons/

Ventyx Biosciences Positive Top-Line Data for Parkinson's The positive safety profile and confirmation of CNS penetration, coupled with biomarker reductions, suggest that VTX3232 could address the ...