A Phase IIa Study to Evaluate the Efficacy and Safety of ZM-H1505R in Combination With Entecavir (ETV) Compared With ETV Monotherapy in Patients With Chronic Hepatitis B Who Have Received ETV Monotherapy for at Least 12 Months

This is a multicenter, randomized, double-blind, placebo-controlled phase IIa study, designed to evaluate the efficacy and safety of ZM-H1505R in combination with Baraclude versus Baraclude monotherapy in adult CHB subjects with HBV DNA <2000 IU/mL but ≥ 50 IU/mL and who have received ETV (0.5 mg, once daily [QD)] monotherapy for at least 12 months.
The study is planned to enroll 90 adult CHB subjects who have received ETV monotherapy for at least 12 months and are still receiving ETV monotherapy (0.5 mg, QD) continuously. Eligible subjects will be randomized in a 1:1:1 ratio into 3 treatment groups. Both HBeAg positive and negative subjects will be included. There will be 20 HBeAg positive subjects and 10 HBeAg negative subjects in each treatment group.
After 48 weeks of treatment with the corresponding regimen, subjects will continue to take Baraclude 0.5 mg QD, as a monotherapy for a 12-week follow-up period for observation of efficacy and safety of ZM-H1505R.

开始日期2022-11-11

申办/合作机构

上海挚盟医药科技有限公司初创企业

[+1]

NCT05470829 / Completed临床1期

A Multiple-center,Randomized,Double-blind,Placebo-controlled,Multiple-dose Study Among Chinese Healthy Subjects and Chronic Hepatitis B Patients to Evaluate Safety,Tolerability,Pharmacokinetics and Preliminary Pharmacodynamics of ZM-H1505R

This phase Ib study included two parts in which Part I was to evaluate the safety and bridge for PK among healthy Chinese subjects and Part II were about study among Chinese chronic hepatitis B virus-infected patients. Study of Part II was carried out following the safety assessment and racial difference evaluation in Part I.

开始日期2021-05-27

申办/合作机构

上海挚盟医药科技有限公司初创企业

100 项与卡农克韦相关的临床结果

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100 项与卡农克韦相关的转化医学

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100 项与卡农克韦相关的专利（医药）

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项与卡农克韦相关的文献（医药）

2023-01-01·Gastro hep advances

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study

Article

作者: Deng, Aiyun ; Wang, Zhe ; Hua, Bo ; Chen, Huanming ; Liang, Bo ; Jiang, Xiuhong ; Liu, Gang ; Lu, Hui ; Jin, Qiu ; Zhang, Zhijun ; Guo, Ruoling ; Xia, Tian

Background and Aims:

Canocapavir (ZM-H1505R) is a small-molecule hepatitis B virus capsid assembly modulator with a novel pyrazole structure. This is the first-in-human study to investigate its safety, tolerability, and pharmacokinetics (PK) following oral administration in healthy subjects.

Methods:

This was a randomized, double-blind, placebo-controlled study including single ascending dose (SAD) study with an additional crossover food-effect arm, and multiple ascending dose study. In SAD, 40 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive a single dose of 25, 75, 150, 300, and 450 mg of Canocapavir or placebo in fasted state. For food-effect study, subjects in the 150 mg cohort of SAD received a second dose (150 mg) of Canocapavir in the fed state after a 7-day washout period. In multiple ascending dose, 24 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive 75, 150, and 300 mg of Canocapavir or placebo once daily for 14 days. The safety and tolerability were assessed using vital signs, physical evaluation, electrocardiogram, laboratory investigations, and adverse events (AEs). Plasma PK parameters measured included area under the curves, C_max, C_min, T_max, and T_1/2.

Results:

Oral administration of single doses (25-450 mg) and multiple doses (75-300 mg) of Canocapavir was well tolerated. The most common AE seen was increased alanine aminotransferase. No dose dependency was observed in incidence and intensity of AEs. Mean plasma area under the curve and C_max of Canocapavir increased dose-proportionally. A significant margin was observed between plasma exposure of Canocapavir and its in vitro anti-hepatitis B virus activity. Food had an effect on its absorption.

Conclusion:

The safety and PK profile of Canocapavir support its further evaluation in chronic hepatitis B patients. The study was registered on ClinicalTrial.gov with the number NCT04220801.

BMC medicine

Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial

Article

作者: Hu, Yue ; Zhang, Hong ; Jiang, Xiuhong ; Guo, Ruoling ; Liu, Jingrui ; Mai, Jiajia ; Chen, Huanming ; Hua, Bo ; Liang, Bo ; Jia, Haiyan ; Wu, Min ; Niu, Junqi ; Liu, Chengjiao ; Zhang, Zhijun ; Lu, Hui ; Ding, Yanhua ; Li, Xiaojiao ; Wang, Zhe ; Zhu, Xiaoxue ; Xia, Tian ; Liu, Gang ; Chen, Hong ; Li, Cuiyun ; Deng, Aiyun

Abstract:

Background:

Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB.

Methods:

This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days.

Results:

Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26–1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively.

Conclusions:

Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection.

Trial registration:

ClinicalTrials.gov, number NCT05470829).

项与卡农克韦相关的新闻（医药）

2023-02-02

·医药观澜

挚盟医药与葛兰素史克就TLR8激动剂达成全球独家许可协议

挚盟医药宣布与葛兰素史克（GSK）就其自主研发的TLR8激动剂CB06达成全球独家许可协议。根据协议，挚盟医药在成功完成1期临床研究后，将允许GSK开发、生产和商业化CB06。如果获得成功，CB06可以作为联合用药或与bepirovirsen进行序贯治疗，有可能为更多乙肝患者提供功能性治愈。其中，bepirovirsen是GSK与Ionis Pharmaceutical联合开发的一款反义寡核苷酸疗法。慢性乙型肝炎是重大的公共卫生问题之一。公开资料显示，乙型肝炎病毒（HBV）感染是肝脏疾病的主要原因，每年约几十万人死于慢性乙型肝炎导致的肝衰竭、肝硬化和肝细胞癌等。乙型肝炎病毒致病机理复杂，现有的治疗药物远不能满足临床需求。 TLR8的全称为Toll样受体8 ，它可识别病原体衍生的单链RNA片段，以触发先天性和适应性免疫反应。研究发现，慢性乙型肝炎与功能失调的免疫反应有关，因此选择性TLR8激动剂被认为可能是一种有效的治疗选择。 CB06是挚盟医药自主研发的一款小分子口服TLR8激动剂，是挚盟研发管线中第2个进入临床试验的创新候选药物。根据挚盟医药早前发布的新闻稿，在临床前研究中，CB06表现出了良好的选择性、活性及安全性，可以在人外周血单核细胞中诱导细胞因子，这些细胞因子能够通过多种免疫介质激活抗病毒功能。与此同时，CB06具有良好的肝靶向特征。 2022年4月，挚盟医药宣布TLR8激动剂CB06已在美国完成1期临床试验首次健康受试者用药。这是一项随机、双盲和安慰剂对照的1期临床研究，目的是评估CB06单次递增剂量在健康成人受试者中的安全性、药代动力学和药效学。对于本次合作，挚盟医药首席执行官（CEO）陈焕明博士表示：“与GSK达成合作是对挚盟医药全球临床研究和自主研发能力的重要认可。在合作过程中，GSK团队丰富的研发经验和国际化视野将大大加速合作项目的研发和商业化进程，也将进一步推进挚盟医药打造国际创新药企业的战略布局。 ”挚盟医药是一家处于临床研发阶段的医药科技新锐，专注于中枢神经系统疾病和肝脏疾病的原创型药物研发。除了TLR8激动剂CB06，挚盟医药的核心项目ZM-H1505R是一个新型乙肝病毒核衣壳抑制剂，目前正在慢性乙肝患者中进行2期临床研究。此外，挚盟的抗癫痫新药CB03正在进行临床1期研究。 ▲挚盟医药产品管线（截图来源：挚盟医药官网）参考资料：[1]挚盟医药与葛兰素史克就TLR8激动剂项目签署全球独家许可协议http://www.core-biopharma.com/news/57.html?l=zh-cn 内容来源于网络，如有侵权，请联系删除。

寡核苷酸合作

2022-12-27

·core-biopharma

Zhimeng Biopharma Announces Dosing of First Subject in Phase II Clinical Trial of Its Novel HBV Capsid Assembly Modulator

Shanghai, China. December 27, 2022. Shanghai Zhimeng Biopharma, Inc. (“Zhimeng”), an innovation-driven biopharmaceutical company focused on the development of innovative drugs for the treatment of chronic hepatitis B and central nervous system diseases, announced dosing of the first participant in Phase II study of its novel HBV capsid assembly modulator Canocapavir (ZM-H1505R) in China/Hong Kong. Following the completion of a Phase Ia study of ZM-H1505R in the United States in 2021 and a Phase Ib study in China in 2022, Zhimeng initiated the Phase IIa trial of ZM-H1505R in China/Hong Kong in August 2022, which is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of ZM-H1505R in combination with Entecavir (ETV) compared with ETV monotherapy in patients with chronic hepatitis B who have been receiving ETV monotherapy for at least 12 months. Zhimeng expects to receive the topline results from this trial in the middle of 2023.

临床2期临床1期

2022-12-26

·医药观澜

速递！挚盟医药抗乙肝新药2期临床完成首例患者给药

▎药明康德内容团队编辑今日（12月26日），上海挚盟医药科技有限公司（以下简称“挚盟医药”）宣布其自主研发的新型乙肝病毒核衣壳抑制剂卡农克韦（canocapavir，ZM-H1505R）在中国大陆、香港地区完成2a期临床试验首例受试者给药。挚盟医药是一家临床阶段的生物制药公司，致力于开发治疗慢性乙型肝炎和严重未满足医疗需求的神经系统疾病的创新药物。ZM-H1505R是该公司开发的一款小分子乙型肝炎病毒（HBV）衣壳组装调节剂，具有新型吡唑结构。它可通过干扰病毒核衣壳的正常形成和阻碍前基因组RNA（PgRNA）的包装，而起到阻止乙肝病毒复制的作用，并有效阻断HBV cccDNA的形成。ZM-H1505R对大多数对其他HBV核衣壳调节剂表现出耐药的HBV变异株具有活性，目前正在评估用于慢性乙型肝炎（CHB）的治疗。挚盟医药于2021年在美国完成了ZM-H1505R的1a期研究，并于2022年在中国完成了该药的1b期研究后。2022年8月，挚盟医药在中国大陆、香港地区启动了ZM-H1505R的2a期试验。这是一项多中心、随机、双盲、安慰剂对照研究，旨在评估ZM-H1505R联合恩替卡韦（ETV）与ETV单药治疗相比在已经接受ETV单药治疗至少12个月的慢性乙型肝炎患者中的有效性和安全性。挚盟医药创始人、董事长兼首席执行官陈焕明博士表示：“我们很高兴能在今年如此困难的环境下如期启动ZH-1505R的2a期临床试验，感谢所有参与本项临床试验的研究者、受试者和临床团队。我们期待能在明年二季度获得本项研究的初步数据，加速推进ZM-H1505R的中国3期临床试验进程，帮助慢性乙肝患者尽早实现功能性治愈。”除了ZM-H1505R，挚盟医药最近还宣布了多项进展：包括已于2022年3月在美国启动针对慢性乙型肝炎开发的新型TLR8激动剂的首次人体1期研究；已于2022年5月在美国首次对其新型小分子KCNQ2/3选择性开放剂进行人体1期研究，该分子拟开发用于治疗难治性癫痫、重度抑郁症（MDD）、渐冻症（ALS）等神经系统疾病。本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床2期临床1期临床3期

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适应症	最高研发状态	国家/地区	公司	日期
慢性乙型肝炎	临床2期	中国	上海挚盟医药科技有限公司初创企业	2022-11-11
慢性乙型肝炎	临床2期	中国香港	上海挚盟医药科技有限公司初创企业	2022-11-11

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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


NCT05470829 (Pubmed)	临床1期	慢性乙型肝炎	10	Canocapavir 50 mg	蓋窪鹽憲顧簾構構壓製(夢構鹽淵鹹觸積選簾齋) = 鹹鏇鏇醖艱衊蓋夢鏇願艱築膚淵繭憲鑰願觸簾 (築衊製製築觸築範醖獵 )	-	2023-03-16
				Canocapavir 100 mg	蓋窪鹽憲顧簾構構壓製(夢構鹽淵鹹觸積選簾齋) = 窪蓋積構積齋鑰夢廠窪艱築膚淵繭憲鑰願觸簾 (築衊製製築觸築範醖獵 )
EASL2022	N/A	慢性乙型肝炎	30	ZM-H1505R 50 mg	簾鬱鏇製窪艱餘蓋壓醖(顧積憲齋蓋窪齋餘鏇範) = 簾餘觸壓鹹鬱繭夢簾範願壓積鬱齋簾鏇鹹壓鬱 (淵膚顧鏇選範構窪積淵 ) 更多	-	2022-06-25
				ZM-H1505R 100 mg	簾鬱鏇製窪艱餘蓋壓醖(顧積憲齋蓋窪齋餘鏇範) = 醖繭網醖壓膚淵繭鹽鑰願壓積鬱齋簾鏇鹹壓鬱 (淵膚顧鏇選範構窪積淵 ) 更多