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 or 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.

开始日期2024-09-20

申办/合作机构

Cerevance, Inc.

NCT06006247

/ Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson's Disease

This is a multicenter, 12-week, placebo-controlled clinical trial of CVN424 150 milligrams (mg) tablets in early, untreated Parkinson's Disease (PD). Participants will be randomized in a 1:1 ratio to CVN424 150 mg or placebo at the Baseline Visit. The purpose of this study is to measure effect on motor features with CVN424 tablets compared to placebo in early, untreated PD and to evaluate the potential of CVN424 to improve motor and non-motor functions in participants with early PD who are not taking dopaminergic or anti-PD therapies.

开始日期2023-09-11

申办/合作机构

Cerevance, Inc.

NCT05635461

/ Completed临床1期

A Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension &Tablet Formulations Including an Assessment of the Effect of Food on the Tablet Formulation in Healthy Adult Volunteers

This is a Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension and Tablet Formulations in Healthy Volunteers Under Fasted and Fed Conditions.

开始日期2022-10-09

申办/合作机构

Cerevance, Inc.

100 项与 CVN-424 相关的临床结果

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100 项与 CVN-424 相关的转化医学

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100 项与 CVN-424 相关的专利（医药）

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项与 CVN-424 相关的文献（医药）

2024-12-03·Science Signaling

Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson’s disease

Article

作者: Saikatendu, Kumar S. ; Murphy, Sean T. ; Lutomski, Corinne A. ; Lam, Jordy H. ; Sun, Hukai ; Schiffer, Hans H. ; Popov, Petr ; Robinson, Carol V. ; Bliesath, Joshua ; Han, Gye Won ; Sadybekov, Anastasiia V. ; Hua, Tian ; Katritch, Vsevolod ; Barekatain, Mahta ; Monenschein, Holger ; Cherezov, Vadim ; Liu, Zhi-Jie ; Russo, Joseph ; Chang, Hao ; Johansson, Linda C. ; Brice, Nicola L. ; Carlton, Mark B. L.

GPR6 is an orphan G protein–coupled receptor with high constitutive activity found in D2-type dopamine receptor–expressing medium spiny neurons of the striatopallidal pathway, which is aberrantly hyperactivated in Parkinson’s disease. Here, we solved crystal structures of GPR6 without the addition of a ligand (a pseudo-apo state) and in complex with two inverse agonists, including CVN424, which improved motor symptoms in patients with Parkinson’s disease in clinical trials. In addition, we obtained a cryo–electron microscopy structure of the signaling complex between GPR6 and its cognate G s heterotrimer. The pseudo-apo structure revealed a strong density in the orthosteric pocket of GPR6 corresponding to a lipid-like endogenous ligand. A combination of site-directed mutagenesis, native mass spectrometry, and computer modeling suggested potential mechanisms for high constitutive activity and inverse agonism in GPR6 and identified a series of lipids and ions bound to the receptor. The structures and results obtained in this study could guide the rational design of drugs that modulate GPR6 signaling.

2024-11-01·EClinicalMedicine

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial

Article

作者: Kieburtz, Karl ; Carlton, Mark ; Matthews, Kim L ; Ellenbogen, Aaron L ; Olanow, C Warren ; Dubow, Jordan ; Brice, Nicola L ; Bexon, Martin ; Dawson, Lee A ; Margolin, David H

Background:

CVN424 is a GPR6 inverse agonist that provides selective pharmacological control of the indirect striatopallidal pathway. We assessed the safety and efficacy of CVN424 as an adjunctive treatment to levodopa for reducing OFF-time in individuals with Parkinson's disease (PD) experiencing motor-fluctuations.

Methods:

This was a randomised, double-blind, placebo-controlled study conducted at 21 sites across the United States to evaluate two doses of CVN424 (NCT04191577). Patients with PD (Hoehn and Yahr stages 2-4) who were on a stable dose of levodopa and experiencing ≥2 h of daily OFF-time were randomised (1:1:1) to receive either once-daily CVN424 (50 mg or 150 mg) or placebo for a 28-day treatment period. The primary endpoints were safety and tolerability. The key secondary endpoint was the change from baseline to Day 27 in OFF-time.

Findings:

The study was conducted from December 23, 2019, to October 14, 2021. Out of 198 participants screened, 141 eligible participants were randomised to one of the three treatment groups (n = 47 per group), and 127 participants completed the 28-day treatment period. The most common treatment emergent adverse events (TEAEs) were headache (2% with CVN424 50 mg, 9% with CVN424 150 mg, and 2% with placebo) and nausea (4% with CVN424 50 mg, 6% with CVN424 150 mg and 2% with placebo). No serious treatment-related adverse events were reported. On Day 27, the mean ± standard deviation (SD) change from baseline in daily OFF-time was -1.3 ± 3.0 h in the CVN424 50 mg group, -1.6 ± 2.5 h in the CVN424 150 mg group, and -0.5 ± 2.9 h in the placebo group. The placebo-adjusted LS mean ± standard error (SE) treatment difference was significant for the CVN424 150 mg dose (1.3 ± 0.56 h, [95 CI% -2.41 to -0.19], nominal p = 0.02).

Interpretation:

Treatment with CVN424 was safe and well-tolerated. Despite the short study duration and small sample size, the 150 mg CVN424 dose provided a clinically meaningful reduction in daily OFF-time. This study supports the development of CVN424 for the treatment of PD.

Funding:

Cerevance.

2023-02-17·ORGANIC PROCESS RESEARCH & DEVELOPMENT

Scalable Synthesis of CVN424, an Inverse Agonist of the GPR6 Receptor

作者: Mu, Changwei ; Yang, Yifang ; Doyle, Kevin J. ; Mistry, Anil ; Ye, Naidong ; Zhou, Yusheng ; Bürli, Roland W. ; Li, Xiaolong ; Wang, Chunhua

The process development of an efficient synthetic route that delivered several kilograms of the drug substance, CVN424, I was described.The synthesis of CVN424, I included diacylation of com. available 3,4-diaminopyridine with di-Et oxalate to give 1,4-dihydropyrido[3,4-b]pyrazine-2,3-dione and chlorination with POCl³ to give 2,3-dichloropyrido[3,4-b]pyrazine hydrochloride , followed by two sequential nucleophilic aromatic substitutions.A final hydrogenation and acetylation of intermediate II provided CVN424, I.Overall, a safe and robust synthesis was developed, which occurred in five linear steps with an overall yield of 15%.

项与 CVN-424 相关的新闻（医药）

2026-04-09

·BioSpace

Cerevance to Present Positive Phase 2 Solengepras Data in Parkinson’s Disease at the American Academy of Neurology 2026 Annual Meeting

Solengepras, a once-daily, oral, non-dopaminergic GPR6 inhibitor, demonstrated meaningful reductions in daily OFF time and improvements in sleep-related symptoms across two Phase 2 trials Meeting presentations highlight the potential of a non-dopaminergic approach in addressing key areas of unmet need in Parkinson’s disease ‍ BOSTON, April 09, 2026 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing targeted therapies for neurodegenerative diseases and obesity, today announced upcoming presentations at the American Academy of Neurology (AAN) 2026 Annual Meeting being held from April 18-22 in Chicago. Details of the poster presentations at the AAN Annual Meeting are as follows:‍ Title: Characteristics of OFF-time Improvement in a Phase Two Study for Parkinson’s Disease (PD) with Solengepras, a Novel GPR6-inhibitor Presenter: Robert Hauser, M.D., M.B.A., Director, Parkinson’s Disease and Movement Disorder Center, University of South Florida; Professor of Neurology, University of South Florida College of Medicine Date/Time: Tuesday, April 21, 2026, 11:45 a.m. CT / 9:45 a.m. PT Title: Solengepras, A Novel GPR6-inhibitor, Shows Potential to Improve Sleep Disturbance in Parkinson’s Disease: Results from the ASCEND Phase Two Trial Presenter: Harini Sarva, M.D., Associate Professor of Clinical Neurology, Weill Cornell Medicine Date/Time: Tuesday, April 21, 2026, 11:45 a.m. CT / 9:45 a.m. PT About Solengepras (CVN424) Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as an adjunctive therapy to levodopa and other anti-Parkinsonian medications in the Phase 3 ARISE trial. About the Pivotal Phase 3 ARISE Trial The multicenter, randomized, double-blind, placebo-controlled Phase 3 ARISE trial is evaluating the efficacy and safety of solengepras as an adjunctive therapy to levodopa and other background Parkinson’s disease medications. The trial is enrolling approximately 330 patients with Parkinson’s disease age 30 and older with motor fluctuations who have an average of three or more hours of total OFF time per day. Study participants are randomized to solengepras 75 mg or 150 mg or placebo once daily for 12 weeks. The primary endpoint is the change from baseline to week 12 in average daily OFF time for solengepras 150 mg versus placebo. Secondary objectives include assessing safety and tolerability and further characterizing the effect of solengepras on other motor symptoms (e.g., ON time), non-motor symptoms (e.g., daytime sleepiness), cognitive function, and several quality-of-life measures (e.g., Movement Disorder Society-UPDRS, PD Questionnaire 39, Clinical Global Impression scale, Patient Global Impression scale). ARISE is being conducted globally at sites in the United States, Europe, and Australia. About Parkinson’s Disease Parkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorder, affecting more than 10 million people worldwide and approximately 1 million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, such as levodopa, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit pro About Cerevance Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative diseases and obesity. Our proprietary platform, N uclear E nriched T ranscript S ort seq uencing (NETSseq), enables identification of potential drug targets from human brain samples expressed in specific cell types, including those at very low levels or within rare cell populations, and whose expression may change as a disease progresses. Our most advanced investigational treatment, solengepras, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. Our second investigational treatment, CVN293, is a highly selective oral inhibitor targeting THIK1 (KCNK13), a two-pore potassium channel family member. CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity. For more information, please visit and follow us on LinkedIn and X . Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: April Dovorany, adovorany@realchemistry.com

临床2期临床结果临床3期

2026-04-08

·BioSpace

Cerevance to Participate in the 25th Annual Needham Virtual Healthcare Conference

BOSTON, April 08, 2026 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing targeted therapies for neurodegenerative diseases and obesity, today announced participation in one-on-one meetings with investors at the 25th Annual Needham Virtual Healthcare Conference being held from April 13-16. About Cerevance Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative diseases and obesity. Our proprietary platform, N uclear E nriched T ranscript S ort seq uencing (NETSseq), enables identification of potential drug targets from human brain samples expressed in specific cell types, including those at very low levels or within rare cell populations, and whose expression may change as a disease progresses. Our most advanced investigational treatment, solengepras, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. Our second investigational treatment, CVN293, is a highly selective oral inhibitor targeting THIK1 (KCNK13), a two-pore potassium channel family member. CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity. For more information, please visit and follow us on LinkedIn and X . Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: April Dovorany, adovorany@realchemistry.com

临床3期细胞疗法

2026-03-10

·BioSpace

Cerevance to Present Phase 2 Trial Results on OFF Time and Sleep‑Related Outcomes with Solengepras in Parkinson’s Disease at AD/PD™ 2026

Post hoc analyses of two Phase 2 trials examine the potential benefits of solengepras, a once-daily, oral, non-dopaminergic GPR6 inhibitor, across Parkinson’s disease populations Phase 2 adjunctive trial data showed a significant reduction in the frequency and duration of OFF time in individuals with Parkinson’s disease experiencing motor fluctuations, largely translating into increased good ON time New Phase 2 ASCEND monotherapy trial demonstrated potential benefit in non-motor symptoms versus placebo, with the largest standardized improvement observed in sleep-related symptoms BOSTON, March 10, 2026 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing targeted therapies for neurodegenerative diseases and obesity, today announced upcoming oral presentations at the AD/PD TM 2026 International Conference on Alzheimer’s & Parkinson’s Diseases being held from March 17-21 in Copenhagen. Details of the oral presentations at AD/PD TM 2026 are as follows:‍ Title: Characteristics of OFF-time improvement in a Phase 2 study for Parkinson’s disease (PD) with solengepras, a novel GPR6 inhibitor Presenter: Karl Kieburtz, M.D., M.P.H., Co-founder, Clintrex Research LLC; Professor of Neurology, University of Rochester Date/Time: Saturday, March 21, 2026, 12:10 p.m. CET / 4:10 a.m. PT Title: Solengepras, a novel GPR6 inhibitor, shows potential to improve sleep disturbance in Parkinson’s disease: Results from the ASCEND Phase 2 trial Presenter: Aaron L. Ellenbogen, D.O., M.P.H., Medical Director, Quest Research Institute; Assistant Professor of Medicine, Oakland University William Beaumont School of Medicine; Neurologist, Parkinson’s Disease and Movement Disorders Center, Michigan Institute for Neurological Disorders Date/Time: Saturday, March 21, 2026, 3:10 p.m. CET / 7:10 a.m. PT About Solengepras (CVN424) Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as an adjunctive therapy to levodopa and other anti-Parkinsonian medications in the Phase 3 ARISE trial. About the Pivotal Phase 3 ARISE Trial The multicenter, randomized, double-blind, placebo-controlled Phase 3 ARISE trial is evaluating the efficacy and safety of solengepras as an adjunctive therapy to levodopa and other background Parkinson’s disease medications. The trial is enrolling approximately 330 patients with Parkinson’s disease age 30 and older with motor fluctuations who have an average of three or more hours of total OFF time per day. Study participants are randomized to solengepras 75 mg or 150 mg or placebo once daily for 12 weeks. The primary endpoint is the change from baseline to week 12 in average daily OFF time for solengepras 150 mg versus placebo. Secondary objectives include assessing safety and tolerability and further characterizing the effect of solengepras on other motor symptoms (e.g., ON time), non-motor symptoms (e.g., daytime sleepiness), cognitive function, and several quality-of-life measures (e.g., Movement Disorder Society-UPDRS, PD Questionnaire 39, Clinical Global Impression scale, Patient Global Impression scale). ARISE is being conducted globally at sites in the United States, Europe, and Australia. About Parkinson’s Disease Parkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorder, affecting more than 10 million people worldwide and approximately 1 million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, such as levodopa, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit pro About Cerevance Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative diseases and obesity. Our proprietary platform, N uclear E nriched T ranscript S ort seq uencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced investigational treatment, solengepras, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. Our second investigational treatment, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13). CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity. For more information, please visit and follow us on LinkedIn and X . Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: April Dovorany, adovorany@realchemistry.com

临床2期临床3期临床结果细胞疗法

100 项与 CVN-424 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
并发症	临床3期	美国	Cerevance, Inc.	2024-09-20
并发症	临床3期	澳大利亚	Cerevance, Inc.	2024-09-20
帕金森病	临床3期	美国	Cerevance, Inc.	2024-09-20
帕金森病	临床3期	澳大利亚	Cerevance, Inc.	2024-09-20
帕金森病	临床3期	捷克	Cerevance, Inc.	2024-09-20
帕金森病	临床3期	意大利	Cerevance, Inc.	2024-09-20
精神运动障碍	临床2期	美国	Cerevance, Inc.	2019-12-02

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06006247 (ASCEND, CTgov)	临床2期	帕金森病	64	CVN424 150 mg (CVN424 150 mg)	鹹膚觸憲窪鏇積艱衊鹹(顧積鹹鏇鬱衊艱鏇夢願) = 積蓋鑰鏇築築蓋艱簾鏇鑰糧襯鬱觸齋夢獵淵鏇 (窪範醖鏇願夢廠壓遞鑰, 1.599) 更多	-	2026-03-23
				Placebo (Placebo)	鹹膚觸憲窪鏇積艱衊鹹(顧積鹹鏇鬱衊艱鏇夢願) = 顧淵願構齋鹽廠選鏇蓋鑰糧襯鬱觸齋夢獵淵鏇 (窪範醖鏇願夢廠壓遞鑰, 1.622) 更多
NCT06006247 (ASCEND, MDS2025)	临床2期	帕金森病	64	Solengepras 150mg	衊憲構鏇鹹衊觸齋鏇膚(遞艱鑰餘鬱餘鹹鹹廠膚): Difference = -0.73, P-Value = 0.75 更多	积极	2025-10-05
				Placebo
NCT04191577 (Biospace) 人工标引	临床2期	帕金森病	-	solengeprassolengepras 50 mg	憲範鑰網廠蓋遞壓鑰糧(積夢餘鏇範鑰鬱膚襯蓋) = 繭築簾製獵衊積蓋窪觸簾網餘鹽鹹糧夢構窪遞 (鏇繭獵膚醖鑰簾製襯構 )	积极	2024-10-21
				solengepras 150 mgsolengepras 150 mg	憲範鑰網廠蓋遞壓鑰糧(積夢餘鏇範鑰鬱膚襯蓋) = 廠獵構繭簾餘鏇築鹹遞簾網餘鹽鹹糧夢構窪遞 (鏇繭獵膚醖鑰簾製襯構 )
NCT05635461 (CTgov)	临床1期	帕金森病	32	CVN424 (Treatment A: CVN424 150 mg Suspension (Fasted))	鏇積鑰蓋構顧窪膚壓鏇(窪鏇襯淵艱獵蓋襯壓繭) = 繭淵醖糧窪鏇壓選鏇範憲艱艱鏇獵鹹憲觸餘窪 (鬱獵憲築蓋獵衊獵窪鹹, 19.3) 更多	-	2024-08-15
				CVN424 (Treatment B: CVN424 150 mg Tablet (Fasted))	鏇積鑰蓋構顧窪膚壓鏇(窪鏇襯淵艱獵蓋襯壓繭) = 遞遞餘構糧繭壓醖壓繭憲艱艱鏇獵鹹憲觸餘窪 (鬱獵憲築蓋獵衊獵窪鹹, 31.8) 更多
NCT04191577 (CTgov)	临床2期	精神运动障碍 \| 帕金森病	136	Placebo (Placebo Arm)	積網醖膚鬱製選製築獵 = 構願衊簾齋憲夢簾選夢襯觸築壓壓簾鏇遞糧製 (遞襯選艱範衊遞鹽廠繭, 蓋簾廠窪鬱鬱齋艱糧鑰 ~ 鬱製糧艱齋鬱壓獵構鑰) 更多	-	2024-07-03
				CVN424 (CVN424 50 mg)	積網醖膚鬱製選製築獵 = 築鏇鏇鹹廠夢夢鑰鹽範襯觸築壓壓簾鏇遞糧製 (遞襯選艱範衊遞鹽廠繭, 鬱構積網遞鑰鑰繭鏇構 ~ 壓簾艱鏇齋繭襯淵壓膚) 更多