CVN424 for Parkinson's Disease

Recruiting at 15 trial locations

Overseen By Julie Daves

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cerevance

Must be taking: Levodopa

Must not be taking: Antipsychotics, Strong CYP3A4/5 inhibitors

Disqualifiers: Atypical parkinsonism, Severe dyskinesias, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CVN424 for individuals with Parkinson's disease who experience motor fluctuations, or changes in movement control. The goal is to evaluate the effectiveness and safety of CVN424 compared to a placebo, with participants taking different doses once daily for 12 weeks. Ideal candidates are those diagnosed with Parkinson's, who have noticeable movement changes and are on stable medications for the condition. Participants must be able to identify their movement states and have a history of responding to the common Parkinson's medication, levodopa. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for Parkinson's disease.

Will I have to stop taking my current medications?

The trial requires that your Parkinson's medications be stable for at least 4 weeks before screening, and certain medications like MAO-B inhibitors need to be stable for 12 weeks. You should not be using strong CYP3A4/5 inhibitors or inducers, or medications with dopamine antagonist activity. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that CVN424 is likely to be safe for humans?

Research has shown that CVN424 is generally safe and well-tolerated in people. In earlier studies, participants took CVN424 once a day without major safety issues. Specifically, the 150 mg dose did not cause any unusual side effects compared to lower doses. This suggests that both 75 mg and 150 mg doses are likely manageable for participants. So far, the studies have reported no serious side effects. Overall, the safety data for CVN424 appears promising. ^{1 2 3 4 5}

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

CVN424 is unique because it targets a novel mechanism in the brain by modulating the G-protein-coupled receptor 6 (GPR6), which is different from the standard dopamine-based treatments for Parkinson's disease like levodopa or dopamine agonists. This approach could lead to fewer side effects related to dopamine, such as dyskinesias or motor fluctuations. Researchers are excited because CVN424 has the potential to improve motor symptoms without the complications associated with current therapies, offering a promising alternative for patients.

What evidence suggests that CVN424 might be an effective treatment for Parkinson's disease?

Research has shown that CVN424, a drug targeting a specific part of the brain, may help treat Parkinson's disease. In animal studies, CVN424 improved movement problems similar to those seen in Parkinson's. Participants in this trial will receive either 75 mg or 150 mg of CVN424, or a placebo. In a study with people, those taking 150 mg of CVN424 felt more alert during the day. These results suggest that CVN424 could help with both movement and non-movement symptoms of Parkinson's disease. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for people with Parkinson's Disease who have motor complications. They must meet specific diagnostic criteria, respond well to levodopa, and experience at least 3 hours of 'OFF' time daily. Participants should be able to walk (with or without help), have a certain cognitive score, maintain stable PD medication use before the trial, and fall within a specified weight range.

Inclusion Criteria

Was your Parkinson’s diagnosis made 10 years ago or less?

In the past six months, have you had fewer than two falls?

Have your Parkinson’s medications stayed the same doses for at least the past 4 weeks?

Exclusion Criteria

Are you currently depressed?

Has a doctor told you that you have dementia or do you feel your thinking and memory are declining?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-daily oral doses of either 75 mg CVN424, 150 mg CVN424, or a matching placebo for 12 weeks

12 weeks

Regular in-person visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1-2 visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• CVN424

Trial Overview The study tests CVN424 at two different doses (75 mg and 150 mg) against a placebo in patients with Parkinson's Disease over 12 weeks. It's randomized and double-blind, meaning neither the researchers nor participants know who gets the real drug or placebo. Successful candidates may join a future open-label extension study.

How Is the Trial Designed?

Group I: CVN424 75 mg Experimental Treatment 1 Intervention

Participants will be administered with oral doses of 75 mg CVN424.

Group II: CVN424 150 mg Experimental Treatment 1 Intervention

Participants will be administered with oral doses of 150 mg CVN424.

Group III: Placebo Placebo Group 1 Intervention

Participants will be administered with placebo.

Who Is Running the Clinical Trial?

Cerevance

Lead Sponsor

Trials

2

Recruited

390+

Published Research Related to This Trial

CVN424 is a first-in-class small molecule that selectively targets the GPR6 receptor, which is important for controlling movement and is implicated in Parkinson's disease; it was found to be safe and well tolerated in a phase 1 study involving healthy volunteers.

The study demonstrated that CVN424 reached peak plasma concentrations within 2 hours and had a mean half-life of 30 to 41 hours, with no serious adverse effects reported, paving the way for further investigation in a phase 2 study for Parkinson's disease patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I, First-in-Human, Healthy Volunteer Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CVN424, a Novel G Protein-Coupled Receptor 6 Inverse Agonist for Parkinson's Disease. Margolin, DH., Brice, NL., Davidson, AM., et al.[2022]

A meta-analysis of six studies involving over 27,000 subjects found that the use of calcium channel blockers (CCBs) is associated with a significantly decreased risk of developing Parkinson's disease, with a pooled relative risk of 0.81.

Both types of CCBs, dihydropyridine and non-dihydropyridine, were effective in reducing the risk of Parkinson's disease, suggesting a potential protective effect of these medications against this neurodegenerative disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers: A Meta-Analysis. Gudala, K., Kanukula, R., Bansal, D.[2020]

A meta-analysis of five studies with over 208,000 calcium channel blocker (CCB) users found that CCB use is associated with a 24% reduction in the risk of developing Parkinson's disease (PD).

Both types of CCBs—dihydropyridine and non-dihydropyridine—showed significant reductions in PD risk, with dihydropyridine users experiencing a 27% reduction and non-dihydropyridine users a 30% reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis. Lang, Y., Gong, D., Fan, Y.[2015]

The study developed a selective antagonist, CVN417, targeting the α6 subunit of nicotinic acetylcholine receptors, which is important for modulating dopamine release and may help in treating movement disorders.

In rodent models, CVN417 effectively reduced tremors, suggesting its potential as a therapeutic option for conditions like Parkinson's disease that involve motor dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of CVN417, a Novel Brain-Penetrant α6-Containing Nicotinic Receptor Antagonist for the Modulation of Motor Dysfunction. Christie, LA., Brice, NL., Rowland, A., et al.[2023]

CVN424 is a highly potent and selective inverse agonist for the GPR6 receptor, showing promise as a novel treatment for Parkinson's disease by improving motor function in preclinical models.

In animal studies, CVN424 demonstrated brain penetration and dose-dependent effects, including increased locomotor activity and reversal of catalepsy, indicating its potential therapeutic efficacy without relying on traditional dopaminergic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CVN424: A Selective and Novel GPR6 Inverse Agonist Effective in Models of Parkinson Disease. Brice, NL., Schiffer, HH., Monenschein, H., et al.[2021]

Citations

1. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00461-9/fulltext

CVN424, a GPR6 inverse agonist, for Parkinson's disease ... Preclinical studies demonstrate that CVN424 is effective in reversing locomotor deficits in animal models of PD, and a phase 1 study showed that ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06553027

To Evaluate the Efficacy of CVN424 in Parkinson's Disease ... This is a randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations.

3. davisphinneyfoundation.org davisphinneyfoundation.org/blog/clinical-trial-cvn424/

The ASCEND Clinical Trial Explores Novel Target in ... The results showed that participants taking 150 mg/day of CVN424, experienced improvement of daytime alertness. Design of the CVN424-203 ...

4. cerevance.com cerevance.com/studies/cvn424

CVN424 The ASCEND clinical study is evaluating whether CVN424, an investigational drug, is safe and effective in improving the motor and non-motor symptoms of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04191577

Study of CVN424 in Parkinson's Disease Patients With ... Following baseline safety and efficacy assessments, subjects will be randomized to receive once-daily doses of either low-dose CVN424, high-dose CVN424, or ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35110393/

A Phase I, First-in-Human, Healthy Volunteer Study to ... We conclude that CVN424, a nondopaminergic compound that modulates a novel therapeutic target, was safe and well tolerated. A phase 2 study in ...