The goal of this clinical trial is to evaluate the long-term safety and tolerability of zagociguat in patients with MELAS who completed study medication treatment in the lead-in study TIS6463-203. TIS6463-204 is evaluating zagociguat in an open-label extension study at the daily dose of 15mg. The study medication is a once daily oral table and will be provided at the clinic and/or shipped to the participant's home. Study assessments will be conducted during clinic visits which will occur at three months and then at six months. Thereafter, clinic visits will occur every six months.

开始日期2025-08-18

申办/合作机构

Tisento Therapeutics, Inc.

NCT06402123

/ Recruiting临床2期

Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)

PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.

开始日期2024-09-10

申办/合作机构

Tisento Therapeutics, Inc.

NCT04798989

/ Terminated临床2期

A Phase 2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CY6463 When Administered to Participants With Alzheimer's Disease and Vascular Pathology

This study is being conducted to test the safety, tolerability, and pharmacokinetics of the investigational drug CY6463 compared with placebo in individuals who are aged 60 years or older and have Alzheimer's disease (AD) along with common cardiovascular risk factors.

开始日期2021-11-02

申办/合作机构

Tisento Therapeutics, Inc.

100 项与 Zagociguat 相关的临床结果

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100 项与 Zagociguat 相关的转化医学

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100 项与 Zagociguat 相关的专利（医药）

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项与 Zagociguat 相关的文献（医药）

2023-12-01·British journal of clinical pharmacology

Randomized placebo‐controlled crossover study to assess tolerability and pharmacodynamics of zagociguat, a soluble guanylyl cyclase stimulator, in healthy elderly

Article

作者: van der Grond, Jeroen ; Glasser, Chad ; Borghans, Laura ; van Kraaij, Sebastiaan J W ; Groeneveld, Geert Jan ; Tripp, Ken ; Winrow, Christopher ; Klaassen, Erica S ; Gal, Pim

Aims:

Dysfunction of nitric oxide‐soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate signalling is implicated in the pathophysiology of cognitive impairment. Zagociguat is a central nervous system (CNS) penetrant sGC stimulator designed to amplify nitric oxide–cyclic guanosine monophosphate signalling in the CNS. This article describes a phase 1b study evaluating the safety and pharmacodynamic effects of zagociguat.

Methods:

In this randomized crossover study, 24 healthy participants aged ≥65 years were planned to receive 15 mg zagociguat or placebo once daily for 2 15‐day periods separated by a 27‐day washout. Adverse events, vital signs, electrocardiograms and laboratory tests were conducted to assess safety. Pharmacokinetics of zagociguat were evaluated in blood and cerebrospinal fluid (CSF). Pharmacodynamic assessments included evaluation of cerebral blood flow, CNS tests, pharmaco‐electroencephalography, passive leg movement and biomarkers in blood, CSF and brain.

Results:

Twenty‐four participants were enrolled; 12 participants completed both treatment periods, while the other 12 participants completed only 1 treatment period. Zagociguat was well‐tolerated and penetrated the blood–brain barrier, with a CSF/free plasma concentration ratio of 0.45 (standard deviation 0.092) measured 5 h after the last dose of zagociguat on Day 15. Zagociguat induced modest decreases in blood pressure. No consistent effects of zagociguat on other pharmacodynamic parameters were detected.

Conclusion:

Zagociguat was well‐tolerated and induced modest blood pressure reductions consistent with other sGC stimulators. No clear pharmacodynamic effects of zagociguat were detected. Studies in participants with proven reduced cerebral blood flow or CNS function may be an avenue for further evaluation of the compound.

2023-08-01·Clinical and translational science

First‐in‐human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS‐penetrant soluble guanylyl cyclase stimulator

Article

作者: Groeneveld, Geert Jan ; Borghans, Laura G. J. M. ; Glasser, Chad ; van Kraaij, Sebastiaan J. W. ; Dijkstra, Francis ; Klaassen, Erica S. ; Gal, Pim ; Winrow, Christopher

Abstract:

Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate, play a role in learning and memory formation. Zagociguat (CY6463) is a novel stimulator of sGC being developed for the treatment of neurodegenerative disease. Single zagociguat doses of 0.3, 1, 3, 10, 20, 30, and 50 mg were administered once to healthy participants in a single‐ascending‐dose phase; then zagociguat 2, 5, 10, and 15 mg was administered q.d. for 14 days in a multiple‐ascending‐dose phase; and, finally, zagociguat 10 mg was administered once in both fed and fasted state in a food‐interaction phase. Safety of zagociguat was evaluated by monitoring treatment‐emergent adverse events, suicide risk, vital signs, electrocardiography, and laboratory tests. Pharmacokinetics of zagociguat were assessed through blood, urine, and cerebrospinal fluid sampling. Pharmacodynamic effects of zagociguat were evaluated with central nervous system (CNS) tests and pharmaco‐electroencephalography. Zagociguat was well‐tolerated across all doses evaluated. Zagociguat exposures increased in a dose‐proportional manner. Median time to maximum concentration ranged from 0.8 to 5 h and mean terminal half‐life from 52.8 to 67.1 h. CNS penetration of the compound was confirmed by cerebrospinal fluid sampling. Zagociguat induced up to 6.1 mmHg reduction in mean systolic and up to 7.5 mmHg reduction in mean diastolic blood pressure. No consistent pharmacodynamic (PD) effects on neurocognitive function were observed. Zagociguat was well‐tolerated, CNS‐penetrant, and demonstrated PD activity consistent with other sGC stimulators. The results of this study support further development of zagociguat.

2021-10-15·ORGANIC PROCESS RESEARCH & DEVELOPMENT

Accelerated Development of a Scalable Synthesis of CY6463, a CNS-Penetrant sGC Stimulator for the Treatment of Neurodegenerative Diseases

作者: Storz, Thomas ; Kissel, William S. ; Wallace, Debra J. ; Balanov, Anna

Soluble guanylate cyclase (sGC) stimulators are small mols. that increase nitric oxide (NO) signaling by binding to sGC, leading to an increase in cyclic guanosine monophosphate productionSuch compounds have previously been studied clin. for noncentral nervous system (CNS) disorders.CY6463 is the first CNS-penetrant sGC stimulator to enter clin. trials and has the potential to pos. impact a range of neurodegenerative diseases.In this paper, we present the development of an efficient, robust, and scalable synthesis of this compound that allowed for rapid generation of larger quantities of material, thereby accelerating advancement into early clin. studies, while minimizing the use of resources.The synthesis features a palladium-catalyzed one-pot Negishi coupling/cyanation sequence and a novel triazole formation from a Boc-protected amidrazone.Optimization of the reactions, safety considerations, and control of impurities, as well as a mechanistic study of the triazole formation reaction, are discussed.

项与 Zagociguat 相关的新闻（医药）

2025-11-03

·GlobeNewswire-Health Care

Tisento Therapeutics Announces Publication of MELAS Interview Study, Incorporating Patients’ Perspectives to Elucidate Symptoms and Impacts of Rare Mitochondrial Disease

Findings Demonstrate the Importance of Addressing Both Fatigue and Cognitive Symptoms of MELASCAMBRIDGE, Mass., Nov. 03, 2025 (GLOBE NEWSWIRE) -- Tisento Therapeutics today announced that the findings from the company’s interview study in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes) were published on October 27, 2025, in the Journal of Patient-Reported Outcomes. Based on qualitative interviews with five expert clinicians and 16 adults with MELAS in North America, the study aimed to identify, describe, and substantiate important and relevant signs, symptoms, and health-related quality-of-life impacts of this rare mitochondrial disease. The publication, entitled “Signs, Symptoms, and Health-Related Quality of Life in MELAS: Measuring What’s Important from the Patient and Clinician Perspectives,” can be viewed here. This groundbreaking work informed the clinical outcome assessments and endpoint strategy for the company’s ongoing global Phase 2b PRIZM study, which is evaluating the impact of investigational zagociguat treatment on fatigue, cognitive performance, and other key aspects of MELAS. “Those living with MELAS have historically faced a lack of understanding about their condition and their lived experiences. This study addresses a critical research gap in this rare disease,” said Kira Mann, chief executive officer of MitoAction. “As this study shows, MELAS manifests in a wide range of symptoms, including fatigue and cognition, and profoundly affects multiple aspects of patients’ lives. Those living with MELAS urgently need treatments that target the most debilitating aspects of this disease.” Patients in the study reported a total of 35 signs and symptoms. The most frequently reported symptoms were physical fatigue (n=15, 93.8%), hearing loss (n=13, 81.3%), mental fatigue (n=12, 75.0%), exercise intolerance (n=11, 68.8%), and memory problems (n=11, 68.8%). In addition, 68 health-related quality-of-life impact concepts emerged, which were categorized into 15 impact domains. The impact domains reported by the most participants were adaptive behaviors (n=14, 87.5%); work impacts (n=14, 87.5%); and emotional function (n=13, 81.3%). “At Tisento, we believe that meaningful innovation starts with listening to the lived experiences of those affected by a disease. We are pleased that the MELAS interview study has advanced the understanding of this rare disease by elucidating both patients’ and physicians’ perspectives about the most important symptoms to address,” said Peter Hecht, Ph.D., chief executive officer of Tisento. “We’re grateful to everyone who participated, as their insights helped shape our clinical program. We are excited to continue advancing zagociguat, an investigational treatment for MELAS with the potential to improve both fatigue and cognitive function.” About the PRIZM Study PRIZM – a Phase 2b Randomized, Placebo-Controlled Trial Investigating Zagociguat in MELAS – is evaluating the efficacy and safety of oral zagociguat 15 mg or 30 mg compared to placebo when administered once-daily for 12 weeks in participants with genetically and phenotypically defined MELAS. The PRIZM study has a crossover design, with two 12-week treatment periods separated by a 4-week washout period. All participants will receive zagociguat during one of the 12-week periods and placebo during the other. Participants who complete treatment in the study have the opportunity to enroll in an open-label extension study. The global PRIZM study is enrolling approximately 44 participants at mitochondrial disease centers of excellence in the U.S., Italy, Germany, United Kingdom, Australia, and Canada. More information may be found at www.tisentotx.com/prizm and ClinicalTrials.gov (NCT06402123). About Zagociguat Zagociguat is a once-daily, oral, clinical-stage investigational medicine with potential to positively impact both peripheral and central nervous system manifestations of mitochondrial diseases. Zagociguat stimulates soluble guanylate cyclase (sGC), an enzyme that is found in virtually every cell in every tissue of the body and is part of a system of cellular mechanisms that control critical physiological functions including neuronal function and blood flow. A first-in-class, brain-penetrant sGC stimulator, zagociguat is hypothesized to rebalance dysregulated cellular pathways in MELAS. By restoring cellular functions that support mitochondria, zagociguat may help restore mitochondrial energy production and physiological function. In a Phase 2a study in patients with MELAS, zagociguat exhibited a favorable safety profile, exposure throughout the body including in the central nervous system, and improvements in neuronal function, mitochondrial function, and blood flow in the brain. Zagociguat is currently being evaluated as a treatment for MELAS in the Phase 2b PRIZM study. Zagociguat received Fast Track designation from the U.S. Food and Drug Administration for the treatment of MELAS. Fast Track is a process designed to facilitate the development and potentially expedite the review of medicines to treat serious conditions and fill an unmet medical need, with the goal of getting important new drugs to patients earlier. For more information, visit www.tisentotx.com/our-science. About Tisento Therapeutics Tisento Therapeutics, a privately held biotech company, is developing novel medicines to treat diseases with significant unmet need, beginning with MELAS and other genetic mitochondrial diseases. Ti sento means “I hear you” in Italian; our approach to innovation begins with listening to patients and then channeling what we learn into decisive actions that shape our research and clinical programs. Tisento is guided by a high-caliber internal team of biopharma veterans and an extensive external network of expert physicians, patient advocacy groups, researchers, industry-leading vendors, and other close collaborators who are partners in our mission to develop meaningful treatments for mitochondrial diseases. Learn more at our website, www.tisentotx.com, or connect with us on LinkedIn, Facebook, X (@tisentotx), or Bluesky. Contact Tisento Media RelationsJessi Rennekamp, Astrior CommunicationsEmail: jessi@astriorcomms.com

临床2期临床结果快速通道

2025-08-20

·GlobeNewswire-Health Care

First PRIZM Study Participant Enrolled in Tisento Therapeutics’ Open-Label Extension Study in MELAS

Participants Who Complete Treatment in Global Phase 2b PRIZM MELAS Study Are Eligible to EnrollCAMBRIDGE, Mass., Aug. 20, 2025 (GLOBE NEWSWIRE) -- Tisento Therapeutics today announced that the first participant has enrolled in the company’s open-label extension study in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes). The extension study (NCT06961344) is evaluating the long-term safety and tolerability of zagociguat in individuals with MELAS who complete treatment in the global Phase 2b PRIZM study, which is expected to complete screening in the next months. The extension study is intended to provide uninterrupted access to zagociguat for clinical trial participants for up to two years and evaluate the long-term safety of zagociguat. “We’re pleased to reach the important milestone of enrolling the first PRIZM study participant into our open-label extension study,” said Peter Hecht, Ph.D., chief executive officer of Tisento. “Enthusiastic engagement by MELAS patients and physicians is powering momentum in our development program, and we look forward to completing PRIZM enrollment in the next few months.” The PRIZM study is actively enrolling in the U.S., Canada, Australia, United Kingdom, Italy, and Germany, and interested individuals are encouraged to discuss participation with their physician. PRIZM is evaluating the impact of zagociguat treatment on fatigue, cognitive performance, and other key aspects of MELAS. The clinical outcome assessments and endpoint strategy for the PRIZM study were informed by Tisento’s interview study in which individuals living with MELAS described the symptoms and impacts of the disease that are most important to them. Participants who complete treatment in PRIZM have the opportunity to enroll in the open-label extension study. About the PRIZM Study PRIZM – a Phase 2b Randomized, Placebo-Controlled Trial Investigating Zagociguat in MELAS – is evaluating the efficacy and safety of oral zagociguat 15 mg or 30 mg compared to placebo when administered once-daily for 12 weeks in participants with genetically and phenotypically defined MELAS. The PRIZM study has a crossover design, with two 12-week treatment periods separated by a 4-week washout period. All participants will receive zagociguat during one of the 12-week periods and placebo during the other. Participants who complete treatment in the study have the opportunity to enroll in an open-label extension study. The global PRIZM study is now enrolling approximately 44 participants at mitochondrial disease centers of excellence in the U.S., Italy, Germany, United Kingdom, Australia, and Canada. For more information, please visit www.tisentotx.com/prizm or ClinicalTrials.gov (NCT06402123). Interested individuals can also reach out to their physicians for participation details. About Zagociguat Zagociguat is a once-daily, oral, clinical-stage investigational medicine with potential to positively impact both peripheral and central nervous system manifestations of mitochondrial diseases. Zagociguat stimulates soluble guanylate cyclase (sGC), an enzyme that is found in virtually every cell in every tissue of the body and is part of a system of cellular mechanisms that control critical physiological functions including neuronal function and blood flow. A first-in-class, brain-penetrant sGC stimulator, zagociguat is hypothesized to rebalance dysregulated cellular pathways in MELAS. By restoring cellular functions that support mitochondria, zagociguat may help restore mitochondrial energy production and physiological function. In a Phase 2a study in patients with MELAS, zagociguat exhibited a favorable safety profile, exposure throughout the body including in the central nervous system, and improvements in neuronal function, mitochondrial function, and blood flow in the brain. Zagociguat is currently being evaluated as a treatment for MELAS in the Phase 2b PRIZM study. Zagociguat received Fast Track designation from the U.S. Food and Drug Administration for the treatment of MELAS. Fast Track is a process designed to facilitate the development and potentially expedite the review of medicines to treat serious conditions and fill an unmet medical need, with the goal of getting important new drugs to patients earlier. For more information, visit www.tisentotx.com/our-science. About Tisento Therapeutics Tisento Therapeutics, a privately held biotech company, is developing novel medicines to treat diseases with significant unmet need, beginning with MELAS and other genetic mitochondrial diseases. Ti sento means “I hear you” in Italian; our approach to innovation begins with listening to patients and then channeling what we learn into decisive actions that shape our research and clinical programs. Tisento is guided by a high-caliber internal team of biopharma veterans and an extensive external network of expert physicians, patient advocacy groups, researchers, industry-leading vendors, and other close collaborators who are partners in our mission to develop meaningful treatments for mitochondrial diseases. Learn more at our website, www.tisentotx.com, or connect with us on LinkedIn, Facebook, X (@tisentotx), or Bluesky. Contact Tisento Media RelationsJessi Rennekamp, Astrior CommunicationsEmail: jessi@astriorcomms.com

临床2期快速通道

2025-06-18

·Pharmaceutical Technology

Tisento’s MELAS treatment receives fast track status from FDA

The company is studying the therapy in the global Phase IIb PRIZM trial. Credit: Volha_R/Shutterstock. Tisento Therapeutics has received fast track designation from the US Food and Drug Administration (FDA) for its investigational oral medicine, zagociguat, for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), a rare mitochondrial disease. Zagociguat acts by stimulating soluble guanylate cyclase (sGC), an enzyme found across every cell in all tissues of the body. Tisento Therapeutics CEO Peter Hecht stated: “People living with MELAS and their families face tremendous challenges and deserve to have treatments that address the aspects of the disease that matter most to them. “We are pleased to receive fast track designation from the FDA in recognition of the MELAS community’s unmet medical needs and the potential of zagociguat to be a meaningful therapeutic option to address both neurological and systemic manifestations of the disease.” Tisento is studying the influence of this brain-penetrant sGC stimulator on cognitive impairment, fatigue and other primary aspects of the disease in the global Phase IIb PRIZM trial, which is currently enrolling in Europe, Australia and North America. The study’s clinical outcome evaluations and endpoint strategy were shaped by insights from people with MELAS, who provided input on the disease’s symptoms and impacts that matter most to them. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence The study is assessing the safety and efficacy of 15 mg or 30 mg of the therapy against a placebo, administered once daily for 12 weeks to those with genetically and phenotypically defined MELAS. All subjects will be given zagociguat in one of the 12-week durations and a placebo during the other. Subjects who conclude the trial will be qualified for an open-label extension trial. MELAS patients often display severe symptoms such as chronic fatigue, muscle weakness, cognitive issues, stroke-like episodes and seizures. With no approved treatments available, present management strategies focus on symptomatic treatments and lifestyle modifications, which fall short of addressing the disease’s profound and persistent effects. Pharmaceutical Technology Excellence Awards - Have you nominated? Nominations are now open for the prestigious Pharmaceutical Technology Excellence Awards - one of the industry's most recognised programmes celebrating innovation, leadership, and impact . This is your chance to showcase your achievements, highlight industry advancements , and gain global recognition . Don't miss the opportunity to be honoured among the best - submit your nomination today! Nominate Now

临床2期快速通道

100 项与 Zagociguat 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
阿尔茨海默症	临床2期	美国	Tisento Therapeutics, Inc.	2021-11-02
乳酸性酸中毒	临床2期	美国	Cyclerion Therapeutics	2020-11-13
MELAS综合征	临床2期	美国	Tisento Therapeutics, Inc.	2020-11-13
脑卒中	临床2期	美国	Cyclerion Therapeutics	2020-11-13
认知障碍	临床1期	美国	Cyclerion Therapeutics	2021-09-10
精神分裂症	临床1期	美国	Tisento Therapeutics, Inc.	2021-09-10
血管性痴呆	药物发现	美国	Cyclerion Therapeutics	2019-04-02

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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


NCT04798989 (CTgov)	临床2期	阿尔茨海默症	12	Placebo (Placebo)	膚廠構顧廠膚遞廠範鑰 = 鏇衊鬱壓壓網齋遞鹽艱鬱網積網構鑰窪製鑰簾 (餘鏇艱範範築遞築簾網, 憲糧選壓願築夢壓構衊 ~ 積築選鹽夢壓構淵顧選) 更多	-	2024-10-30
NCT04798989 (CTgov)	临床2期	阿尔茨海默症	12	CY6463 (CY6463)	膚廠構顧廠膚遞廠範鑰 = 鹽齋鹹構齋製衊憲願膚鬱網積網構鑰窪製鑰簾 (餘鏇艱範範築遞築簾網, 襯構齋鏇網齋淵鬱鬱觸 ~ 鬱膚廠餘膚衊鑰壓遞糧) 更多	-	2024-10-30
NCT04475549 (CTgov)	临床2期	MELAS综合征	8	IW-6463 Tablets	獵醖鹽鬱壓糧構糧餘遞 = 襯範鬱夢築窪構觸積網繭憲壓齋顧構構鑰鹽夢 (願網齋糧憲遞鑰憲憲憲, 範餘壓願膚餘顧醖蓋範 ~ 襯膚願構壓廠顧繭鏇網) 更多	-	2023-11-15
NCT04972227 (CIAS, Corporate Publications) 人工标引	临床1期	认知功能障碍	48	CY 6463	膚構製網遞觸積醖觸艱(鏇廠鹽鹽遞醖窪鏇製鏇) = 蓋選窪艱鑰鏇構鹽築繭壓餘製糧壓餘鬱鏇膚淵 (艱壓顧鏇壓觸範鏇衊鏇 ) 更多	积极	2022-07-28
NCT04972227 (CIAS, Corporate Publications) 人工标引	临床1期	认知功能障碍	48	Placebo	-	积极	2022-07-28
Biospace 人工标引	临床2期	线粒体病	8	CY6463	醖壓網襯鹽鹽簾積醖構(壓鹽製鬱憲鑰鹹壓鬱簾) = 壓構窪憲壓夢憲蓋選艱廠願廠窪壓醖築膚範糧 (衊範齋鏇鬱夢膚選廠夢 ) 更多	积极	2022-06-28