CVN424 for Parkinson's Disease

Recruiting at 25 trial locations

Overseen By Celina Scholl

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

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations. Participants will be randomized to receive once-daily oral doses of either 75 milligrams (mg) CVN424, 150 mg CVN424, or a matching placebo for 12 weeks. Participants who successfully complete this study and retain eligibility/suitability will be invited to participate in a future open-label extension (OLE) study.

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 CVN424 safe for humans?

In a study with healthy volunteers, CVN424 was generally well tolerated with no serious or severe side effects observed, and no significant changes in vital signs or lab results. ^{1 2 3 4 5}

Eligibility Criteria

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

I've been on stable medication for drooling for 30 days without expecting changes.

Average of ≥ 3 h total OFF time/day on Screening home diaries, with at least 2.5 hours OFF on each diary day.

Approved as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)

Exclusion Criteria

I often feel dizzy when standing up and need medication for it.

I experience specific types of movement issues without peak-dose involuntary movements.

Tests positive at Screening for drugs of abuse (opiates, tetrahydrocannabinol [THC], methadone, cocaine, and amphetamines [including ecstasy]).

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States 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. [2022]

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

Development of CVN424: A Selective and Novel GPR6 Inverse Agonist Effective in Models of Parkinson Disease. [2021]

3. Egypt pubmed.ncbi.nlm.nih.gov

Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers: A Meta-Analysis. [2020]

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

Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis. [2015]

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

Discovery of CVN417, a Novel Brain-Penetrant α6-Containing Nicotinic Receptor Antagonist for the Modulation of Motor Dysfunction. [2023]