Double Blind, Randomized, Placebo Controlled, Study to Evaluate the Safety of HRX215 in Patients Post Major Hepatectomy, Preceded by an Open Pilot Phase in Patients Post Minor Hepatectomy Due to Metastases of a Colon Carcinoma

The goal of this clinical trial is to learn if HRX215 is safe and tolerable in adults who have undergone surgical removal of metastatic tumor(s) due to colorectal carcinoma in the liver.
The main question it aims to answer are:
1. to learn about the safety of HRX215
2. to learn about how the body absorbs, distributes, and gets rid of HRX215 . Researchers will compare HRX215 to a placebo (a look-alike substance that contains no drug) to see what medical problems participants have when taking HRX215.
Participants will:
Take HRX215 or a placebo twice a day for 28 days Daily visits for 7 days for checkups and tests which may either be in the hospital or outpatient after 3 days. Clinic visits every two weeks for the next two visits. The visit at two weeks may be a home visit or clinic visit. Additional clinic visits 3 months and 6 months after the start of treatment

开始日期2024-11-01

申办/合作机构

HepaRegeniX GmbH初创企业

100 项与 HRX-215 相关的临床结果

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100 项与 HRX-215 相关的转化医学

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100 项与 HRX-215 相关的专利（医药）

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项与 HRX-215 相关的文献（医药）

2024-03-01·Cell1区 · 生物学

First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure

1区 · 生物学

Article

作者: Zacarias, Magdalena Ortiz ; Koenigsrainer, Alfred ; Chen, Harvey ; Haag, Mathias ; Zwirner, Stefan ; Sipos, Bence ; Laufer, Stefan ; Amiot, Bruce ; Jia, Yao ; Zhou, Wei ; Abu Rmilah, Anan A ; Moschopoulou, Athina A ; Heinkele, Georg ; Rist, Elke ; Longerich, Thomas ; Klotz, Sabrina ; Trompak, Omelyan ; Gruenheit, Nicole ; Felgendreff, Philipp ; Albrecht, Wolfgang ; Shapiro, David ; Nyberg, Scott ; Nelson, Erek ; Biskup, Saskia ; Theisgen, Stephan ; Muerdter, Thomas E ; Michalak, Gregory ; Gries, Katharina ; Premsrirut, Prem K ; Schuette, Svenja ; Kloevekorn, Philip ; Selig, Roland ; Pfaffenroth, Bent ; Weissbach, Markus ; Zender, Lars ; Poso, Antti ; Cui, Wei ; Minshew, Anna ; Li, Kewei ; Ab, Eiso ; Wuestefeld, Torsten ; Jung, Birgit ; Schwab, Matthias

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.

项与 HRX-215 相关的新闻（医药）

2024-07-10

·Firstwordpharma

HepaRegeniX bags €15M to advance liver regeneration therapy

HepaRegeniX said Wednesday it has successfully closed a €15 million ($16.2 million) series C round to advance a new therapy designed to jumpstart the liver's regenerative powers. The financing was led by Vesalius Biocapital IV with participation from existing investors Novo Holdings, Boehringer Ingelheim Venture Fund, and High-Tech Gründerfonds.HRX-215 is a small molecule inhibitor of MKK4, designed to unlock the regenerative capacity of hepatocytes and boost liver regeneration in patients. According to HepaRegeniX, the therapy holds promise for people with liver metastases, primary liver tumours, and those undergoing liver transplantation."With the new funds, HepaRegeniX will advance with its clinical plans for a Phase Ib study in the US and an international Phase IIa study to enhance liver recovery and prevent liver failure," commented Elias Papatheodorou, who transitions from chair of the board to CEO.The company also announced the appointment of Linda Greenbaum as chief medical officer. "MKK4 is a key regulator of liver regeneration, and MKK4 inhibition has been shown to induce liver regeneration after a partial hepatectomy," she said. "With this mode of action, HRX-215 has an immense potential to improve outcomes for patients who are currently not able to undergo potentially curative surgical resections due to liver tumours."The funding comes on the heels of promising preclinical data and a Phase I trial. In a paper published in the journal Cell earlier this year, researchers said "we are convinced that the observed antisteatotic and antifibrotic activity provides a very good basis for further testing of HRX215 in chronic liver disease.""We envision that HRX215 harbours the potential to push the boundaries of oncological liver surgery," they said, adding "perioperative HRX215 treatment holds the promise to safely prevent PHLF [post-hepatectomy liver failure] after liver resections and will make more extensive resections possible, thus allowing a potential curative perspective for more patients with colorectal cancer liver metastases and also for patients suffering from primary liver carcinomas."HepaRegeniX raised a €9 million series A and €11 million series B in 2017 and 2020, respectively.

临床1期临床2期高管变更

2024-07-10

·BioSpace

HepaRegeniX raises €15 million Series C round to advance clinical development of HRX-215 for liver regeneration

Funds to support Phase Ib clinical trial of HRX-215 in the US and an international multicenter Phase IIa clinical trial in liver regeneration Elias Papatheodorou moves from Chair of the Board to CEO of HepaRegeniX Dr. Linda Greenbaum joins HepaRegeniX as CMO TUEBINGEN, Germany, July 10, 2024 (GLOBE NEWSWIRE) -- HepaRegeniX GmbH, a clinical stage company developing a novel regenerative therapy for the treatment of acute and chronic liver diseases, today announced the closing of a Series C round led by Vesalius Biocapital IV with participation of existing investors Novo Holdings, Boehringer Ingelheim Venture Fund (BIVF), and High-Tech Gründerfonds (HTGF). The new funds of €15 million will be used to advance the clinical development of the Company’s clinical candidate HRX-215. As part of the financing, Fabienne Roussel, Partner at Vesalius Biocapital, joins the Non-Executive Board of Directors. Elias Papatheodorou will become Chief Executive Officer, moving from Chair of the Board. Elias Papatheodorou, Chair of the Board, said “We are thrilled to secure this significant financing, which underscores the confidence our investors have in our science and our capabilities to bring effective treatments to patients suffering from liver diseases. With the new funds, HepaRegeniX will advance with its clinical plans for a Phase Ib study in the US and an international Phase IIa study to enhance liver recovery and prevent liver failure.” HRX-215 is a small molecule inhibitor of Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4). Inhibition of MKK4 unlocks the regenerative capacity of hepatocytes and can strongly boost liver regeneration in patients. This is highly relevant for patients with liver metastases or primary liver tumors, as resection of the tumors is the only curative therapeutic approach. Liver regeneration is also key in liver transplant and especially in enabling left liver lobe living donor transplant. This strategy could significantly reduce waiting list for liver transplant candidates. Promising preclinical data have confirmed HRX-215’s capacity for liver regeneration, and HepaRegeniX has successfully completed a Phase I trial. These results have been published in the prestigious journal Cell. “Vesalius Biocapital is excited to support HepaRegeniX as it progresses into the next phase of clinical development for HRX-215. There is an immense need for a treatment that can induce liver regeneration in patients suffering from liver damage, liver tumors, as well as in transplant settings. HRX-215 has potential to help these patients and make a meaningful impact on their lives. I look forward to working with HepaRegeniX’ excellent leadership team to advance this promising treatment candidate,” commented Fabienne Roussel, Partner at Vesalius Biocapital IV. Importantly, to take HepaRegeniX through the next stages of clinical development and value creation, Dr. Linda Greenbaum is joining HepaRegeniX as Chief Medical Officer (CMO). She brings extensive expertise and experience in clinical development and translational medicine. She recently served as Executive Director, Translational Medicine at Novartis in the US. Before joining Novartis, she held the position of Director of Clinical Development at Janssen R&D and served on the faculty of Thomas Jefferson University and University of Pennsylvania where she led a research laboratory investigating liver regeneration and fibrosis. Dr. Greenbaum holds an MD from the Columbia University Vagelos College of Physicians and Surgeons. “I am honored to join HepaRegeniX at such a critical juncture in its development,” added Dr. Linda Greenbaum, Chief Medical Officer of HepaRegeniX. “MKK4 is a key regulator of liver regeneration, and MKK4 inhibition has been shown to induce liver regeneration after a partial hepatectomy. With this mode of action, HRX-215 has an immense potential to improve outcomes for patients who are currently not able to undergo potentially curative surgical resections due to liver tumors, and other patient groups affected by liver failure. I look forward to working with the talented team at HepaRegeniX to advance the clinical development of HRX-215 through Phase II trials and beyond, with the ultimate goal of improving outcomes for patients with liver diseases worldwide." Elias Papatheodorou concluded “It is a pleasure to welcome Dr. Linda Greenbaum to our leadership team. With her extensive knowledge and expertise, she will guide the future clinical development of HRX-215. With our new funding and the extension to our experienced leadership team, we hope to bring a much-need therapy to patients suffering from liver diseases.” info@heparegenix.com For media inquiries: MC Services AG Katja Arnold, Dr. Regina Lutz +49 89 210 228-0 UK: Shaun Brown M: +44 7867 515 918 heparegenix@mc-services.eu About HepaRegeniX GmbH – Since 2017, HepaRegeniX has successfully discovered and developed several drug candidates for the treatment of acute and chronic liver diseases based on a novel proprietary molecular target Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4). The first MKK4 inhibitor HRX-215 recently completed Phase 1 clinical testing. MKK4 is a key regulator of liver regeneration and suppression of MKK4 unlocks the regenerative capacity of hepatocytes even in severely diseased livers. This new and unique therapeutic concept was discovered by Prof. Lars Zender and his research group at the University Hospital Tuebingen, Germany. Investors in HepaRegeniX include Vesalius Biocapital IV, the Boehringer Ingelheim Venture Fund (BIVF), Novo Holdings A/S, Coparion, High-Tech Gründerfonds (HTGF) and Ascenion GmbH.

临床1期临床2期高管变更

2024-03-26

·药明康德

肝病治疗新希望？潜在“first-in-class”小分子登《细胞》，临床试验已启动！

▎药明康德内容团队编辑许多严重肝病患者的肝脏再生能力有限，现今亦无恢复肝脏再生能力的疗法，这使得这类患者的唯一治疗选择是肝脏移植，然而肝脏供体的不足限制了这类患者获得合宜的治疗。近期一项发表在《细胞》杂志上的研究有望打破这一困境。研究发现，一种名为HRX-215的潜在“first-in-class”小分子能够促进大型肝脏切除术后肝脏的愈合与再生。该药物已在1期临床试验中展现良好的安全性与药代动力学特性，有望成为预防或治疗因肝肿瘤切除等原因所造成肝衰竭的潜在疗法。研究人员在过去的研究中发现，双特异性激酶MKK4是肝细胞再生的主要调节器，通过抑制MKK4，可以激发在急性或慢性损害中受损肝脏的内源性再生功能。但遗憾的是，目前尚缺乏可在临床上应用的小分子药物来针对性地抑制MKK4。基于这些初步发现，研究人员进一步开发了针对MKK4的小分子抑制剂HRX-215，并对其进行了详尽的体外及体内研究。实验结果显示，猪模型在进行85%肝脏切除时会发生致命的肝切除术后肝衰竭（PHLF），然而HRX215手术前、后的治疗可成功预防PHLF的发生并显著提升猪的生存期，显示出HRX215促进肝脏再生方面的潜力。这一发现有望为肝移植后治疗人类PHLF和与肝移植后病理相关的小肝综合征（SFSS）提供新的治疗策略。▲HRX215可避免猪在接受85%肝切除术后发生肝衰竭并提升猪的生存率（参考资料[1]）为了评估HRX215的安全性、耐受性及药代动力学特性，研究人员对48名男性健康志愿者开展了一项安慰剂对照的探索性1期临床试验。结果显示，无论是HRX215治疗组还是安慰剂组，均未报告严重不良事件，且轻至中度不良反应的发生率相似，两组之间的全血细胞计数也没有显著差异。进一步分析确认，HRX215具有良好的药代动力学特性，这些初步临床结果为未来开展针对广泛肝脏肿瘤切除术后或小体积肝移植后预防和治疗肝功能衰竭的2期临床研究奠定了基础。▲HRX215在1期临床试验中展现良好的安全性与药代动力学特性（图片来源：参考资料[1]）综上所述，本研究展示了HRX215在推进肝脏肿瘤手术方面的潜力。HRX215的围手术期应用有望在肝脏切除后安全、有效地预防PHLF，同时使得进行更广泛的肝脏切除手术成为可能，为众多结直肠癌肝转移患者和原发性肝癌患者带来潜在的治愈希望。在肝衰竭治疗中，活体肝移植是一种可行方案。然而，对于体型正常的患者而言，从健康捐赠者获取的肝脏左叶往往体积过小，存在小肝综合征的风险。鉴于HRX215能够快速促进肝脏再生，其有望被潜在应用于安全地将小体积的左叶肝脏移植物植入成人受者体内，从而有助于解决肝移植领域面临的器官短缺问题。正如这项研究的共同通讯作者Scott Nyberg博士所言：“这一发现不仅有望改善肝衰竭的治疗、提高活体肝移植的安全性，甚至有可能在某些情况下避免肝移植。”大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Zwirner S, Abu Rmilah AA, Klotz S, Pfaffenroth B, Kloevekorn P,et al. First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure. Cell. 2024 Mar 8:S0092-8674(24)00225-3. doi: 10.1016/j.cell.2024.02.023. Epub ahead of print. PMID: 38490194.[2] Next milestone in the treatment of liver tumors and acute and chronic liver diseases，Retrieved March 19, 2024, from https://www.medizin.uni-tuebingen.de/en-de/das-klinikum/pressemeldungen/628[3] Researchers find promise in new potential treatment for liver failure，Retrieved March 19, 2024, from https://newsnetwork.mayoclinic.org/discussion/researchers-find-promise-in-new-potential-treatment-for-liver-failure/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。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床1期临床2期临床结果

100 项与 HRX-215 相关的药物交易

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