A Phase 2B, Randomized, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rencofilstat in Adult Subjects With Nonalcoholic Steatohepatitis and Advanced Liver Fibrosis

This is a randomized, double-blind, placebo-controlled, parallel-dosing, multi-center study to evaluate the efficacy and safety of Rencofilstat as evidenced by histopathological improvements in fibrosis in adult NASH subjects with F2 or F3 fibrosis (NASH CRN system). Antifibrotic biomarker activity will be evaluated on an exploratory basis.

开始日期2022-10-15

申办/合作机构

Hepion Pharmaceuticals, Inc.

EUCTR2021-005185-18-IT / Not yet recruiting临床2期

ASCEND-NASH: A PHASE 2B, RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CRV431 IN ADULT SUBJECTS WITH NONALCOHOLIC STEATOHEPATITIS AND ADVANCED LIVER FIBROSIS - ASCEND-NASH

开始日期2022-10-05

申办/合作机构

Hepion Pharmaceuticals, Inc.

NCT05461105 / Completed临床2期

ALTITUDE NASH: A Phase 2, Randomized, Multi-Center, Open-Label Study to Evaluate the Safety and Efficacy of Rencofilstat in Adult Subjects With Nonalcoholic Steatohepatitis Stage 3 Fibrosis

This is a randomized, open-label, parallel-dosing, multi-center study to evaluate the safety and efficacy of rencofilstat as evidenced by assessing changes in the HepQuant Shunt Disease Severity Index Score (DSI), safety labs, and clinical events in adult NASH subjects with compensated Fibrosis stage F 2/3. Antifibrotic biomarker activity will be evaluated on an exploratory basis.

开始日期2022-03-15

申办/合作机构

Hepion Pharmaceuticals, Inc.

100 项与 Rencofilstat 相关的临床结果

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100 项与 Rencofilstat 相关的转化医学

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100 项与 Rencofilstat 相关的专利（医药）

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7,064

项与 Rencofilstat 相关的文献（医药）

2024-12-31·Hematology (Amsterdam, Netherlands)

High- vs regular-dose recombinant human thrombopoietin plus cyclosporine A in patients with newly diagnosed non-severe aplastic anemia: a retrospective cohort study

Article

作者: Yang, Yuan ; Yang, Chen ; Chen, Miao ; Hu, Qinglin ; Han, Bing

BACKGROUND:

Cyclosporine A (CsA) and regular doses of recombinant human thrombopoietin (rhTPO) can accelerate platelet recovery in patients with non-severe aplastic anemia (NSAA). However, it is unclear whether CsA plus rhTPO at a higher dose can further increase the efficacy.

METHODS:

Data from patients with newly diagnosed NSAA, who had been treated with CsA in combination with different doses of rhTPO between February 2021 and August 2021 at Peking Union Medical College Hospital, were reviewed. All the enrolled patients had been treated with CsA at 3-5 mg/(kg/d), and patients were further classified into high-dose (with rhTPO 30000U qd × 14 days for 2 months) group or regular-dose (with rhTPO 15000U qd × 7days for 3 months) group. The treatment response and therapy-related adverse events were compared.

RESULTS:

36 patients including 16 (44.4%) in the high-dose and 20 (55.6%) in the regular-dose group were enrolled. The baseline characteristics were compatible between the two groups. The platelet counts were significantly higher at 1/3/6 months in the high-dose group (p = 0.028, 0.0063 and p = 0.040, respectively). The high-dose group had a significantly shorter time to platelet transfusion independence ([1 (0.5-6) months vs 2.5 (1-12) months, p = 0.040]). There was no significant difference in overall response and complete response rate between the two groups at 1/3/6/12 months (p > 0.05). Treatment-related morbidities were similar between the two groups (p > 0.05).

CONCLUSIONS:

Adding a higher dose of rhTPO can further accelerate platelet recovery and platelet transfusion independence in patients with newly diagnosed NSAA.

2024-02-01·Journal of hazardous materials

Metabolic network and proteomic expression perturbed by cyclosporine A to model microbe Escherichia coli

Article

作者: Zhu, Fang ; Yang, Meng ; Du, Daolin ; Qin, Huaming

Cyclosporine A (CsA) is a model drug that has caused great concern due to its widespread use and abuse in the environment. However, the potential harm of CsA to organisms also remains largely unknown, and this issue is exceptionally important for the health risk assessment of antibiotics. To address this concern, the crosstalk between CsA stress and cellular metabolism at the proteomic level in Escherichia coli was investigated and dissected in this study. The results showed that CsA inhibited E. coli growth in a time-dependent manner. CsA induced reactive oxygen species (ROS) overproduction in a dose- and time-dependent manner, leading to membrane depolarization followed by cell apoptosis. In addition, translation, the citric acid cycle, amino acid biosynthesis, glycolysis and responses to oxidative stress and heat were the central metabolic pathways induced by CsA stress. The upregulated proteins, including PotD, PotF and PotG, controlled cell growth. The downregulated proteins, including SspA, SspB, CstA and DpS, were regulators of self-feedback during the starvation process. And the up- and downregulated proteins, including AtpD, Adk, GroS, GroL and DnaK, controlled energy production. These results provide an important reference for the environmental health risk assessment of CsA.

2024-02-01·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

γ-Cyclodextrin metal-organic frameworks as the promising carrier for pulmonary delivery of cyclosporine A

Article

作者: Huang, Yongpeng ; Tang, Hui ; Liu, Dongxin ; Meng, Xiangyan ; Zou, Zhiyun ; Liu, Yanli ; Chen, Bo

γ-Cyclodextrin metal-organic frameworks (CD-MOFs) are considered as a green and biocompatible material with great potential in drug delivery systems. Original CD-MOFs show the poor aerosol properties, which limit the application in pulmonary drug delivery. To improve the in vitro deposition properties, herein, we synthesized CD-MOFs by the vapor diffusion method using a series of modulators to achieve better pulmonary delivery of cyclosporine A (CsA). The results showed that blank CD-MOFs and drug loaded CD-MOFs prepared with different modulators all preserved the cubical shape, and exhibited the similar crystal form, structural characteristics, thermal behaviors and release properties. In addition, drug loaded CD-MOFs prepared with polyethylene glycol 10000 (PEG 10000) as a modulator exhibited better in vitro aerosol performance than those of synthesized using other modulators, and the in vivo pharmacokinetics data demonstrated that the bioavailability of CsA could be significantly enhanced by inhalation administration of drug loaded CD-MOFs compared with oral administration of Neoral®. The repeated dose inhalation toxicity also confirmed the fine biocompatibility of CD-MOFs as the carrier for pulmonary drug delivery. Therefore, the results demonstrated CD-MOFs as the promising carrier could be used for pulmonary drug delivery.

102

项与 Rencofilstat 相关的新闻（医药）

2024-04-23

·Pharmaceutical Technology

Hepion shelves Phase II NASH trial amid shallow cash resources

Hepion has “begun wind-down activities” for the programme as it assesses alternative strategies. Image credit: Shuttestock/Pasuwan. Hepion Pharmaceuticals has called it quits on a Phase IIb trial investigating the biotech’s lead drug candidate for the treatment of non-alcoholic steatohepatitis (NASH). The US company, which uses artificial intelligence and deep machine learning to develop drugs, cited resource constraints as the reason for shelving the trial called ASCEND-NASH. Hepion stated that it has already “begun wind-down activities”. The study was investigating rencofilstat – an oral small molecule that inhibits Cyclophilin B, an important regulator of collagen production. Hepion states that blocking the action of this protein can reduce collagen secretions and fibrotic scarring. The future of Hepion’s NASH programme was already up in the air following a restructuring plan announced in December 2023. The company announced it was pursuing a new strategy that cut operating costs by 60%. At the time, ASCEND-NASH’s enrolment was already paused, with its viability under evaluation. A total of 151 subjects were enrolled in the trial against a target of 336. From that cohort, 80 subjects completed the year-on visit. See Also: Sanofi gears up for approval of its BTK inhibitor, meets Phase III endpoint Hepion’s executive chairman John Brancaccio said: “Given the number of enrolled NASH patients to date and the low probability of generating relevant efficacy data to support a registrational trial with our current cash resources, we have opted to wind down the programme and assure that patients are transitioned out of the trial in a safe and compliant manner.” After pulling the plug on its ASCEND-NASH programme, Hepion said it will continue to explore strategic alternatives. NASH, also known as metabolic dysfunction-associated steatohepatitis (MASH), is a condition where fat builds up in the liver. This can potentially cause liver damage or cirrhosis. The first NASH treatment was approved by the US Food and Drug Administration (FDA) last month. Madrigal Pharmaceuticals ’ Rezdiffra (resmetirom) gained the agency nod after a race that involved several big pharma players. According to GlobalData’s patient-based forecast, Rezdiffra is expected to generate $1bn in global sales in 2027. GlobalData is the parent company of Clinical Trials Arena .

临床2期上市批准

2024-04-22

·药研发

【药研发0423】开拓雄秃新药Ⅱ期临床积极 | 博锐创合放射性显影剂上Ⅰ期临床...

「本文共：15条资讯，阅读时长约：3分钟」今日头条开拓雄秃新药Ⅱ期临床积极。开拓药业新型靶向雄激素受体（AR）的蛋白降解嵌合体（PROTAC）新药GT20029用于治疗男性雄激素性脱发的中国Ⅱ期临床达到了主要终点。与安慰剂相比，GT20029（0.5% QD，1.0% BIW）治疗患者12周后，目标区域内非毳毛数（TAHC）较基线的平均变化达到统计学显著性（16.80根/㎡vs6.69根/㎡，11.94根/㎡vs7.36根/㎡）；GT20029耐受性良好。开拓药业计划尽快开展Ⅲ期临床及美国Ⅱ期临床。国内药讯1.诗健乳腺癌ADC获批Ⅲ期临床。上海诗健生物靶向Trop-2的ADC药物ESG401获国家药监局临床许可，即将针对“经内分泌治疗进展或不适合接受内分泌治疗且在转移阶段的已既往接受过至少一线系统性化疗的HR+/HER2-转移性乳腺癌”适应症开展Ⅲ期临床试验。在早期临床中，ESG401在三阴性乳腺癌（TNBC）患者中ORR为36.3%，DCR为63.6%；在HR+/HER2-乳腺癌患者中的ORR为61.5%，DCR为76.9%。2.恒瑞艾司氯胺酮抑郁研究见刊BMJ。恒瑞医药宣布其艾司氯胺酮用于预防产后抑郁的研究成果在线发表于《英国医学杂志》。数据显示，与对照组相比，艾司氯胺酮治疗组产妇在产后42天时，抑郁发作的患病率显著降低（6.7%vs25.4%，风险比=0.26）；治疗组产妇的爱丁堡抑郁评分和汉密尔顿抑郁评分也更低。患者药物不良反应症状短暂且呈自限性、不需药物干预。3.博锐创合放射性显影剂上Ⅰ期临床。苏州博锐创合宣布其自主研发的用于诊断原发性和转移性脑部肿瘤的正电子发射计算机断层显像（PET）示踪剂[18F]BF3-BPA注射液已在I期临床中完成首例受试者入组，该项试验由复旦大学附属中山医院石洪成主任医师牵头开展。[18F]BF3-BPA是一种新型氨基酸类似物分子，可特异性地聚集在肿瘤组织，具有较高的瘤脑比（T/B），即该药物可使肿瘤病灶与正常脑组织的影像对比明显。4.辉瑞整合素β6 ADC中国获批IND。Seagen公司1类生物药SGN-B6A获CDE临床试验默示许可，拟用于治疗晚期实体瘤。SGN-B6A是一款靶向整合素β6（ITGB6）的抗体偶联药物（ADC），在海外已处于Ⅲ期临床阶段，正在评估SGN-B6A与多西他赛化疗相比治疗复发性非小细胞肺癌的效果。去年3月，辉瑞已以总价值约430亿美元收购Seagen公司并将其纳入旗下公司。5.百济神州FIC双抗报IND。百济神州1类生物制品注射用BGB-B2033的临床试验申请获CDE受理。这是百济神州申报的第2款双抗药物，靶点推测为Claudin6/CD3或MUC1/CD16a。MUC1/CD16a双抗差异化在于更高的CD16a亲和力，CD16a与MUC1臂空间距离近，差异化设计强化了NK细胞效应和肿瘤细胞杀伤作用；Claudin6/CD3双抗则旨在通过低抗原依赖性和旁观者效应的设计克服抗原异质性。国际药讯1.FDA将接受MRD指标作为加速批准的新替代终点。FDA肿瘤药物咨询委员会（ODAC）一致投票（12：0）支持使用微小残留病（MRD）作为新的替代终点，用以支持多发性骨髓瘤药品的加速批准。两项荟萃分析显示，MRD与患者的PFS和OS之间存在很强的个体相关性。MRD通过检视患者骨髓样本残留的癌细胞数量来评估患者的肿瘤负荷，可能可以为药物疗效提供良好的中间指标。2.K药辅助治疗肾癌Ⅲ期研究见刊NEJM。默沙东PD-1疗法Keytruda（pembrolizumab）用于术后中、高级别复发风险的肾细胞癌（RCC）患者辅助治疗的Ⅲ期KEYNOTE-564研究成果已发表于《新英格兰医学杂志》上。中位随访为57.2个月时，Keytruda辅助治疗显著改善了患者的无病生存期（DFS），使疾病复发或死亡风险降低28%；同时，改善了患者的总生存期（HR=0.62，P=0.005），更提高了患者两年期总生存率（91.2%vs86.0%）。临床中没有患者因Keytruda的治疗导致死亡。3.GSK启动新冠疫苗联合RSV疫苗Ⅲ期临床。葛兰素史克RSV重组蛋白疫苗RSVPreF3 0A在Clinicaltrials.gov网站上注册一项Ⅲ期临床试验，拟评估RSVPreF3 0A与新冠mRNA疫苗（奥密克戎XBB.1.5）联合接种时的免疫原性、安全性和反应原性，并与50岁及以上成年人单独接种疫苗进行比较。该项研究预计于2025年5月完成。目前，辉瑞/BioNTech、Modenra、赛诺菲也正在积极开发新冠、RSV、流感的二联或者三联疫苗。4.Silence公司降血脂疗法早期研究见刊JAMA。Silence公司RNAi疗法zerlasiran用于脂蛋白（a）-Lp（a）水平≥150 nmol/L的健康受试者和稳定动脉粥样硬化心血管疾病（ASCVD）患者的Ⅰ期临床研究成果已发表于《美国医学会杂志》。Zerlasiran旨在通过靶向降解LPA基因转录的mRNA来降低Lp（a）的产生。数据显示，Zerlasiran（300mg、600mg）单次给药365天时，受试者Lp（a）浓度较基线下降30%和29%；zerlasiran耐受性良好，常见的不良反应为头痛（33%）。5.Metsera公司融资开发减肥新药。Metsera公司宣布完成2.9亿美元融资，以用于推进其主打项目GLP-1R激动剂，以及胰岛淀粉样肽/降钙素双重激动剂（DACRA）和靶向GLP-1/GIP/胰高血糖素的单分子GGG疗法等产品组合的临床进展，应用于减肥、肥胖和代谢相关疾病的治疗。此轮融资由ARCH Venture Partners领投，F-Prime Capital、GV、Mubadala Capital、Newpath Partners、SoftBank Vision Fund 2等投资者参投。6.Hepion公司终止开发II期MASH新药。因为资金有限，Hepion公司宣布将终止亲环蛋白B抑制剂Rencofilstat治疗代谢相关脂肪性肝炎（MASH）的IIb期ASCEND-NASH研究。在II期ALTITUDE-NASH研究中，Rencofilstat治疗患者的疾病严重程度指数（DSI）评分较基线显著降低1.62分（p<0.05）。此前，该新药已获FDA授予用于治疗MASH的快速通道资格，以及治疗肝细胞癌（HCC）的孤儿药资格。医药热点1.AI将帕金森病药物设计提速十倍。英国剑桥大学研究人员使用人工智能（AI）技术大幅加快了帕金森病治疗方法的开发。他们设计并使用了一种基于AI的策略，来识别阻止α-突触核蛋白（帕金森病的特征蛋白）聚集的小分子，将初始筛查过程加快了10倍，成本缩减至千分之一。研究结果发表在新一期《自然·化学生物学》杂志上。2.西班牙医院用“治疗犬”激励病人。西班牙巴塞罗那一所医院和一个提倡用宠物进行辅助治疗的基金会发起一项活动，将“治疗犬”带到重症病房与患者互动，以缓解患者的紧张情绪，激励他们与病魔抗争。据悉，医生将会分析患者在接受“治疗犬”辅助治疗前后的唾液样本，来检查皮质醇等压力指标是否会降低，以及催产素和血清素等与健康相关的指标是否会增加。3.安医大一附院静脉手术中心启用。近日，安徽医科大学第一附属医院静脉手术中心在该院南区正式开诊。安医大一附院静脉手术中心依托血管外科诊疗优势，设置日间静脉手术病房和血管外科手术室，24小时内完成入院、手术、术后观察及出院全过程，通过便捷的“一站式”就医服务方式，为广大患者提供下肢静脉疾病诊断和治疗、下肢静脉曲张微创日间手术、腿部毛细血管扩张美学治疗等优质服务。评审动态 1. CDE新药受理情况（04月21日) 2. FDA新药获批情况（北美04月19日）股市资讯上个交易日 A 股医药板块 -0.06%涨幅前三跌幅前三万孚生物+15.34% 特一药业-10.01%ST 吉药+13.55% 哈三联 -9.95%同和药业+12.34% 大理药业-9.65%【恒瑞医药]子公司苏州盛迪亚收到国家药监局签发的“注射用卡瑞利珠单抗”临床试验批准通知书。【贵州百灵】公司产品“银丹心脑通软胶囊”获批首家中药二级保护品种，保护期七年。【康希诺】公司产品“冻干b型流感嗜血杆菌结合疫苗”收到国家药监局药物临床试验批准通知书。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

临床3期抗体药物偶联物临床2期并购临床结果

2024-04-22

·Firstwordpharma

Cash crunch forces Hepion to halt mid-stage MASH study of rencofilstat

Hepion Pharmaceuticals’ shares lost a third of their value after the company decided to halt its mid-stage programme for rencofilstat in metabolic dysfunction-associated steatohepatitis (MASH) due to financial constraints. The drugmaker will seek strategic alternatives to pursue further development of the cyclophilin inhibitor.The Phase IIb ASCEND-NASH study kicked off in August 2022 and planned to investigate the safety and efficacy of rencofilstat versus placebo over 12 months in 336 participants. However, enrolment was stopped in April last year after 150 people were randomised. Hepion noted that nearly 80 participants had currently completed the one-year follow-up, with an additional 40 lined up for safety assessments.“Given the number of enrolled [MASH] patients to date and the low probability of generating relevant efficacy data to support a registrational trial with our current cash resources, we have opted to wind down the programme,” explained Hepion’s executive chairman John Brancaccio. He confirmed there were no safety issues associated with the drug in the study.Hepion had earlier announced a restructuring plan to preserve capital by slashing operating costs by approximately 60%, thus extending its cash runway into the second quarter of 2025. Several players, including big pharmas such as Eli Lilly and Novo Nordisk, are battling it out in the competitive MASH arena. However, the MASH debutant crown was snatched by Madrigal after clinching FDA approval for Rezdiffra (resmetirom) last month (for related analysis, read KOL Views Q&A: Leading endocrinologist lays out challenges ahead as Madrigal launches Rezdiffra in MASH).

临床2期上市批准

100 项与 Rencofilstat 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肝纤维化	临床2期	美国	Hepion Pharmaceuticals, Inc.	2020-06-23
肝纤维化	临床2期	波多黎各	Hepion Pharmaceuticals, Inc.	2020-06-23
非酒精性脂肪性肝炎	临床2期	美国	Hepion Pharmaceuticals, Inc.	2020-06-23
非酒精性脂肪性肝炎	临床2期	波多黎各	Hepion Pharmaceuticals, Inc.	2020-06-23
细菌感染	临床1期	美国	Hepion Pharmaceuticals, Inc.	2019-07-09
乙型肝炎	临床1期	美国	Hepion Pharmaceuticals, Inc.	2019-07-09
多发性骨髓瘤	临床前	美国	Hepion Pharmaceuticals, Inc.	2023-01-18

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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


NASH_TAG2024	N/A	代谢功能障碍相关的脂肪肝病 ProC3 \| ALT \| AST	-	Rencofilstat 225 mg QD	糧醖繭窪醖選顧獵範鏇(簾簾壓構膚膚鏇構餘簾) = 38 treatment-related AEs in the trial. No subjects discontinued the trial due to treatment-related AE, and only 1 treatment-related AE was > Grade 2 構鏇積鹹齋襯築蓋襯廠 (積壓廠壓製鑰膚艱窪夢 )	积极	2024-01-04
ALTITUDE-NASH (GlobeNewswire) 人工标引	临床2期	代谢功能障碍相关的脂肪肝病	-	rencofilstat 225 mg	鏇積製鏇鏇醖願艱網顧(遞遞簾鏇鬱遞壓觸構築) = 鏇蓋衊鹽壓簾選襯構窪製獵選鹹夢醖顧淵範積 (窪鬱糧觸鏇壓網糧糧襯, -44.3 ~ -13.4)	积极	2023-11-13
NCT04480710 (AMBITION, NASH_TAG2022)	临床2期	非酒精性脂肪性肝炎 transaminases \| ELF-score \| Pro-C3 ... 更多	43	CRV431 75 mg	遞構願艱鹹鹽願餘製膚(襯蓋積廠艱簾鬱憲廠鹹) = 鬱鬱顧醖獵鏇鑰簾遞膚蓋願顧選鬱憲遞齋衊範 (網簾醖獵鹽選憲鏇願醖 ) 更多	积极	2022-01-06
NCT04480710 (AMBITION, NASH_TAG2022)	临床2期	非酒精性脂肪性肝炎 transaminases \| ELF-score \| Pro-C3 ... 更多	43	CRV431 225 mg	遞構願艱鹹鹽願餘製膚(襯蓋積廠艱簾鬱憲廠鹹) = 築範願鏇遞鏇範蓋願範蓋願顧選鬱憲遞齋衊範 (網簾醖獵鹽選憲鏇願醖 )	积极	2022-01-06
NASH_TAG2020	N/A	-	-	CRV431	壓糧餘製鬱鹹夢膚鑰繭(鹽壓願窪艱鏇齋憲艱網) = 醖夢鏇選願範繭製繭範築蓋窪廠醖衊選廠夢範 (選鬱選糧鏇鑰餘膚範餘 ) 更多	积极	2020-01-09
EASL2019	临床1期	HBV DNA \| HBsAg \| HBeAg ... 更多	32	CRV431 75 mg	壓餘繭觸願襯夢蓋獵網(餘鏇衊壓鹹夢鬱餘願廠) = Safety results demonstrated that CRV431 was well tolerated with no serious adverse events (SAE), no dose-limiting toxicities or dose-dependent adverse events. Overall, the incidence of adverse events and laboratory abnormalities was low and similar among cohorts. All AEs were mild and not drug related. 積簾觸糧顧窪範膚構廠 (廠繭觸餘衊衊艱淵網壓 ) 更多	积极	2019-04-12
EASL2019	临床1期	HBV DNA \| HBsAg \| HBeAg ... 更多	32	CRV431 225 mg		积极	2019-04-12