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 ; Hua, Tian ; Sadybekov, Anastasiia V. ; Han, Gye Won ; 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）

2025-09-22

·GlobeNewswire-Health Care

Cerevance to Present Phase 2 Data on Solengepras in Parkinson’s Disease at the 2025 International Congress of Parkinson's Disease and Movement Disorders

Phase 2 ASCEND trial of solengepras, a novel, non-dopaminergic GPR6 inhibitor, showed evidence of potential benefit in functional and non-motor symptoms in patients with early-stage Parkinson’s diseaseSolengepras was generally well-tolerated during the 12-week study and a low rate of dopaminergic side effects were observed BOSTON, Sept. 22, 2025 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing targeted therapies for neurodegenerative diseases and obesity, today announced an upcoming oral presentation at the 2025 MDS International Congress of Parkinson's Disease and Movement Disorders being held from October 5-9 in Honolulu. The presentation will share findings from the Phase 2 ASCEND study of solengepras, an investigational, non-dopaminergic GPR6 inhibitor being evaluated in patients with early-stage Parkinson’s disease. Results from the trial include analyses of functional and non-motor measures, together with safety observations. Details of the presentation at the 2025 MDS International Congress are as follows: Title: Solengepras: An Investigational Therapy with Potential Benefits on Functional and Non-Motor Measures in Parkinson’s Disease (PD) (Abstract #942) Presenter: Stuart Isaacson, MD, Director and Founder, Parkinson’s Disease and Movement Disorders Center of Boca RatonDate/Time: Monday, October 6, 2025, 12:30 p.m. – 1:30 p.m. HST/ 3:30 p.m. – 4:30 p.m. PTLocation: Room 312, Hawaii Convention Center, Honolulu, HI “Sharing Phase 2 data on solengepras at the MDS Congress reflects our dedication to advancing innovative approaches in Parkinson’s disease,” said Craig Thompson, CEO of Cerevance. “We are deeply appreciative of the investigators and patients who contributed to the ASCEND study, and we welcome the opportunity to engage with the global movement disorders community at this important meeting.” 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 medication in the Phase 3 ARISE trial. About CerevanceCerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative and central nervous system-controlled metabolic disorders. Our proprietary platform, Nuclear Enriched Transcript Sort sequencing (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 therapy, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor for the potential treatment of binge eating disorder and schizophrenia. Our third 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 www.cerevance.com 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

2025-09-22

·cerevance.com

Cerevance to Present Phase 2 Data on Solengepras in Parkinson’s Disease at the 2025 International Congress of Parkinson's Disease and Movement Disorders

What’s a Rich Text element?The rich text element allows you to create and format headings, paragraphs, blockquotes, images, and video all in one place instead of having to add and format them individually. Just double-click and easily create content. Static and dynamic content editingA rich text element can be used with static or dynamic content. For static content, just drop it into any page and begin editing. For dynamic content, add a rich text field to any collection and then connect a rich text element to that field in the settings panel. Voila! How to customize formatting for each rich textHeadings, paragraphs, blockquotes, figures, images, and figure captions can all be styled after a class is added to the rich text element using the "When inside of" nested selector system. What’s a Rich Text element? The rich text element allows you to create and format headings, paragraphs, blockquotes, images, and video all in one place instead of having to add and format them individually. Just double-click and easily create content. Static and dynamic content editing A rich text element can be used with static or dynamic content. For static content, just drop it into any page and begin editing. For dynamic content, add a rich text field to any collection and then connect a rich text element to that field in the settings panel. Voila! How to customize formatting for each rich text Headings, paragraphs, blockquotes, figures, images, and figure captions can all be styled after a class is added to the rich text element using the "When inside of" nested selector system.

临床2期

2025-07-11

·GlobeNewswire-Health Care

Cerevance Announces Presentations at the Alzheimer's Association International Conference 2025

Data from the Phase 1 clinical trial of novel KCNK13 inhibitor showed good CNS exposure and was generally well-toleratedProprietary NETSseq platform explores the key potential role of astrocytes in Alzheimer’s disease ‍BOSTON, July 11, 2025 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative diseases and obesity, today announced upcoming presentations at the Alzheimer's Association International Conference (AAIC) 2025 being held in Toronto from July 27-31, 2025. Details of the poster presentations at AAIC 2025 are as follows: Title: CVN293, an Investigational Inhibitor of KCNK13 Targeting NLRP3-Mediated Neuroinflammation in Neurodegenerative Disease: A Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics (#106386) Session Date/Time: Monday, July 28, 2025, 7:30 a.m. – 4:15 p.m. ET Title: NETSseq unveils deep molecular insights into astrocyte function in Alzheimer’s disease in the human brain (#106433) Session Date/Time: Wednesday, July 30, 2025, 7:30 a.m. – 4:15 p.m. ET About NETSseqOur proprietary platform, Nuclear Enriched Transcript Sort sequencing (NETSseq), enables the identification of subtle molecular changes that drive disease progression. By analyzing brain tissue from a diverse pool of over 20,000 donors, ranging in age from 8 to 104, and including both healthy individuals and those with various central nervous system (CNS) disorders, NETSseq allows us to identify targets that are expressed at very low levels, are present in rare cell types, or change over time as a disease progresses. This transformative tool provides deep insights into the molecular drivers of disease within specific cell populations, expanding our understanding and treatment of neurodegenerative diseases. It enables us to pursue therapies that directly address underlying disease mechanisms. Our platform has been instrumental in the development of our investigational assets, forming a cornerstone of our innovative approach to CNS drug discovery. About CVN293CVN293 is an investigational, highly selective oral inhibitor of the potassium two pore domain channel subfamily K member 13 (KCNK13). By selectively inhibiting KCNK13, a potentially novel regulator of NLRP3 inflammasome activation, CVN293 aims to reduce neuroinflammation and slow disease progression in a variety of neurodegenerative disorders. This mechanism may provide a disease-modifying approach for challenging CNS disorders. Additionally, modulation of KCNK13 may have therapeutic benefit in obesity. KCNK13 was identified by Cerevance’s proprietary NETSseq platform. About CerevanceCerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative and central nervous system-controlled metabolic disorders. 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 the motor and non-motor symptoms of Parkinson's disease. Our second investigational therapy, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor for the potential treatment of binge eating disorder and schizophrenia. Our third investigational treatment, CVN293, is a highly selective investigational oral inhibitor targeting KCNK13. CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity. For more information, please visit www.cerevance.com and follow us on LinkedIn and X. Contacts Cerevance: Johnna Simões, ir@cerevance.com Media:April Dovorany, adovorany@realchemistry.com, +1-262-909-8739

临床1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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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
精神运动障碍	临床2期	美国	Cerevance, Inc.	2019-12-02

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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


NCT04191577 (Biospace) 人工标引	临床2期	帕金森病	-	solengeprassolengepras 50 mg	範鏇鬱餘醖夢獵製窪願(鏇壓鏇艱範鏇構鬱衊蓋) = 鬱衊觸製鬱夢衊網艱糧鹽膚選餘願夢願齋積遞 (蓋範淵夢餘鬱鏇願鹹窪 )	积极	2024-10-21
				solengepras 150 mgsolengepras 150 mg	範鏇鬱餘醖夢獵製窪願(鏇壓鏇艱範鏇構鬱衊蓋) = 選壓願網鹽壓醖窪鹹鹹鹽膚選餘願夢願齋積遞 (蓋範淵夢餘鬱鏇願鹹窪 )
NCT05635461 (CTgov)	临床1期	帕金森病	32	CVN424 (Treatment A: CVN424 150 mg Suspension (Fasted))	鑰壓製窪範獵網繭衊壓(艱築夢醖遞繭壓鏇觸夢) = 鏇鹽憲顧網夢構繭構鑰鹽窪構餘鏇窪餘壓範繭 (鹹齋觸築鬱遞衊觸網積, 19.3) 更多	-	2024-08-15
				CVN424 (Treatment B: CVN424 150 mg Tablet (Fasted))	鑰壓製窪範獵網繭衊壓(艱築夢醖遞繭壓鏇觸夢) = 鹹衊簾鏇窪積觸鑰選糧鹽窪構餘鏇窪餘壓範繭 (鹹齋觸築鬱遞衊觸網積, 31.8) 更多
NCT04191577 (CTgov)	临床2期	精神运动障碍 \| 帕金森病	136	Placebo (Placebo Arm)	醖鏇鹹選廠鹽顧範積糧 = 構鹹糧蓋鏇網衊淵艱鑰鑰製艱餘顧醖遞憲壓衊 (繭鹽襯廠獵淵蓋餘壓蓋, 齋窪獵鹽廠簾願鏇廠壓 ~ 簾艱蓋憲淵網壓壓積夢) 更多	-	2024-07-03
				CVN424 (CVN424 50 mg)	醖鏇鹹選廠鹽顧範積糧 = 膚齋夢遞選顧蓋淵醖遞鑰製艱餘顧醖遞憲壓衊 (繭鹽襯廠獵淵蓋餘壓蓋, 壓餘艱餘鹽選齋鬱壓鑰 ~ 襯醖憲廠遞獵齋構積構) 更多