A Randomized, Placebo-controlled, Parallel-group, Investigator- and Participant-blinded Phase 2a Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in an Adult Population With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP)

This Phase 2a clinical trial will evaluate the effectiveness, safety, and tolerability of increasing dose strengths of an oral daily medication, DFV890, administered for 12 weeks, or a single s.c. dose of MAS825, to reduce key markers of inflammation related to CVD risk, such as IL-6 and IL-18, in approximately 28 people with known coronary heart disease and TET2 or DNMT3A CHIP (VAF ≥2%).

开始日期2024-02-15

申办/合作机构

Novartis Pharmaceuticals Corp.

CTIS2022-501406-36-00 / Recruiting

- CDFV890G12101

开始日期2023-12-14

申办/合作机构

Novartis Pharma AG

NCT06031844 / Recruiting临床2期

A Randomized, Placebo-controlled, Parallel-group, Investigator- and Participant-blinded Phase 2a Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Elevated hsCRP

This Phase 2a clinical trial will evaluate the effectiveness, safety, and tolerability of increasing dose strengths of an oral daily medication, DFV890, administered for 12 weeks, to reduce key markers of inflammation related to CVD risk, such as IL-6 and IL-18, in approximately 24 people with known heart disease and an elevated marker of inflammation, hsCRP.

开始日期2023-10-16

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 IFM-2427 相关的临床结果

登录后查看更多信息

100 项与 IFM-2427 相关的转化医学

登录后查看更多信息

100 项与 IFM-2427 相关的专利（医药）

登录后查看更多信息

项与 IFM-2427 相关的文献（医药）

2023-10-01·European Journal of Pharmacology

Research progress of NLRP3 inflammasome and its inhibitors with aging diseases

Review

作者: Guo, Chun ; Gou, Tingting ; Shi, Jianyou ; Tang, Guoyuan ; Yu, Dongke ; Yuan, Zhuo

In recent years, a new target closely linked to a variety of diseases has appeared in the researchers' vision, which is the NLRP3 inflammasome. With the deepening of the study of NLRP3 inflammasome, it was found that it plays an extremely important role in a variety of physiological pathological processes, and NLRP3 inflammasome was also found to be associated with some age-related diseases. It is associated with the development of insulin resistance, Alzheimer's disease, Parkinson's, cardiovascular aging, hearing and vision loss. At present, the only clinical approach to the treatment of NLRP3 inflammasome-related diseases is to use anti-IL-1β antibodies, but NLRP3-specific inhibitors may be better than the IL-1β antibodies. This article reviews the relationship between NLRP3 inflammasome and aging diseases: summarizes some of the relevant experimental results reported in recent years, and introduces the biological signals or pathways closely related to the NLRP3 inflammasome in a variety of aging diseases, and also introduces some promising small molecule inhibitors of NLRP3 inflammasome for clinical treatment, such as: ZYIL1, DFV890 and OLT1177, they have excellent pharmacological effects and good pharmacokinetics.

2023-06-01·Infection

DFV890: a new oral NLRP3 inhibitor—tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function

Article

作者: Perez, Romulo Omar Flores ; Pabel, Steffen ; Fernandez, Alberto A. ; Pink, Isabell ; Terskikh, Mikhail M. ; Amido, Florencia Heredia ; Kiseleva, Maria ; Bhatnagar, Sushma ; Ortega, Maria L. Morales ; Singh, Ram ; Bauernfeind, Stilla ; Agrawal, Ankit ; Kist, Graziela Regina ; Marcos, Maria Celeste ; Rodriguez, Brenda Nohemi Lozano ; Gatlik, Ewa ; Vasileva, Elena ; Cardozo, Celia ; Rodionova, Olga Vasilievna ; Sag, Sabine ; Vishnevsky, Alexander ; VanDen Berg, Jan Williem ; de Carvalho Rezende, Ederlon Alves ; Paraeva, Olga Sergeevna ; Ramirez, Erick Joel Rendon ; Fernandez, Alberto Alfredo ; Sementsov, Konstantin Valerievich ; Barbosa, Gynara Rezende ; Ganova, Olga Sergeevna ; Vergara, Adrian Martinez ; Datta, Avijatri ; Bachman, Marcus ; Shearman, Nicole ; Lancee, Gerieke ; Farronay, Milagros Ivette Maguina ; Pashkevich, Vladimir Vladimirovich ; Kurguzova, Dariya ; Zerega, Natalia ; Bhopale, Shweta ; Repnikov, Ilia ; Ore, Danilo Joel Salazar ; Flores, Ernesto Moises Zavala ; Gaygolnik, Tamara Valerievna ; Perez, Diego Luis Carrillo ; Ramos, Eduarda Annoni ; Krylov, Andrey Alexandrovich ; Belekhov, George Arkadievich ; Olzik, Ilona ; Goebeler, Maria-Elisabeth ; Velayuthaswamy, Nandagopal ; Fernandes, Caio Cesar ; Pinzhina, Valeria Nikolaevna ; Hitzenbichler, Florian ; Gans, Stephanus J. ; Maier, Lars ; Bacci, Marcelo Rodrigues ; Pandit, Anuja ; Unnithan, Mauila Raghavan Jaymohan ; Zeller, Judith ; Leisner, Ulf ; Saha, Amitabha ; Ripfel, Sarah ; Martynov, Aleksey Viktorovich ; Geismann, Florian ; Srinivasan, Nagarajan ; Kaneesan, Kalaiyamishan ; Costa, Maria Belen ; Lazarenko, Ilya Vyacheslavovich ; Mehes, Beata ; Serrano, Diego Rodriguez ; de Olivera, Ellen Pierre ; Osornio, Jose Sifuentes ; Bhattacharjee, Abhishek ; Smolyarchuk, Elena Anatolievna ; Morozov, Evgeny ; Gounder, Senthil Kumar Mothu ; Krishnamurthy, Srikanth ; Rezende, Ederlon ; Mc Harry, Kirsten ; Sommer, Ulrike ; Kumar, Balbir ; Vishnevsky, Alexander Yurievich ; Vaidyanathan, Venkatraman ; Esze, Tamas ; Srikanth, Ambika ; Brigante, Jorge Alejandro ; Stadnik, Claudio Marcel Berdun ; Radchenko, Elena Nikolaevna ; Lammens, Martine ; Panhuis, Esther ; Kotov, Mikhail E. ; Sayehli, Cyrus Michael ; Tiwari, Pawan ; Tidemandsen, Casper ; Katagarov, Dmitry Nikolaevich ; Benfield, Thomas ; Vishneva, Elena Mikhailovna ; Bagu, Ana Maria ; Hanses, Frank ; Soriano, Joan ; Lubnow, Matthias ; Budhraja, Akshay ; Ratre, Brajesh Kumar ; Jaoude, Caio Vinicius Gouvea ; Garkavi, Dmitriy Andreevich ; Toth, Krisztina Kormosoi ; Madurka, Ildiko ; Nalin, Sabrina ; Boom, Lisenka ; Rendon, Adrian ; Iharos, Dora ; Weismann, Dirk ; del Pino, Ramon Mendoza ; Ortiz, Adrian Camacho ; Messnikov, Oleg ; Bustios, Enrique Renzo Morello ; Hakansson, Kjell ; Abramov, Vladislav Gennadievich ; Meiser, Karin ; Orihuela, Boris Galin ; Klinker, Hartwig ; Frey, Anna ; Blinova, Elena Vladimirovna ; Hinovker, Vladimir Vladimirovich ; Zykov, Vladislav Anatolievich ; Kharlamova, Svetlana ; Stoll, Mathias ; Medina, Miguel Angel Jandete ; Schulze, Petra ; Malacize, Vania Quinato ; Gatalsky, Konstantin Konstantinovich ; Alferov, Sergey Petrovich ; Garcia, Felipe ; Moncivais, Berenice Soto ; Pedersen, Karen Brorup Heje ; Vig, Saurabh ; Boeve-Epping, Nancy ; Antonov, Vladimir Nikolaevich ; Scharf, Natascha ; Martynenko, Tatiana Ivanovna ; Trufanov, Konstantin Vasilievich ; Bondareva, Yulia Andereevna ; Snyman, Elizma ; Junge, Guido ; Isakova, Anna Pavlovna ; Ignatova, Galina Lvovna ; Ulrik, Charlotte S. ; McHarry, Kirsten ; Rudikh, Oleg Vladimirovich ; Franco, Gaston ; Viladomiu, Alex Soriano ; Hupf, Julian ; Ahmed, Nadia Johanna ; Filik, Henrique ; Hejja, Maria ; Ragognete, Henrique Gitti ; Welte, Tobias ; Ulrik, Charlotte Suppli ; Mohan, Anant ; Soriano, Joan B. ; Grebneva, Irina Viktorovna ; Egorova, Ekaterina Aleksandrovna ; Bhan, Swati

BACKGROUNDCoronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm.METHODSThis randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety.FINDINGSBetween May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals.INTERPRETATIONDFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS.TRIAL REGISTRATIONClinicalTrials.gov, NCT04382053.

2021-12-01·Cytokine & Growth Factor Reviews2区 · 医学

The role and transformative potential of IL-19 in atherosclerosis

2区 · 医学

Review

作者: Jiyao Xing ; Xinlin Liu ; Wujun Chen ; Dongming Xing ; Shuai Wang

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Traditionally, IL-19 was thought to be expressed in only immune cells, but studies revealed that IL-19 is also expressed in multiple atherosclerotic plaque cell types, but not normal arteries, in humans and mice. IL-19 reduces the development of atherosclerosis via multiple mechanisms, including balancing cholesterol metabolism; enhancing Th2 immune cell polarization; reducing the inflammatory response; and reducing the proliferation, migration and chemotaxis of vascular smooth muscle cells (VSMCs). Clinical and/or animal studies have primarily aimed to achieve regression and/or stabilization of atherosclerotic plaques, with regression in particular indicating a very good drug response. Most antiatherosclerotic drugs in current clinical use, including atorvastatin and alirocumab, target hyperlipidemia. Several other drugs have also been investigated in clinical trials as anti-inflammatory agents; the development of some of these agents has been terminated (canakinumab, darapladib, varespladib, losmapimod, atreleuton, setileuton, PF-04191834, veliﬂapon, and methotrexate), but others remain in development (ziltivekimab, tocilizumab, Somalix, IFM-2427, anakinra, mesenchymal stem cells (MSCs), colchicine, everolimus, allopurinol, and montelukast). Most of the tested drugs have shown a limited ability to reverse atherosclerosis in animal studies. Interestingly, recombinant IL-19 (rIL-19) was shown to reduce atherosclerosis development in a time- and dose-dependent manner. A low dose of rIL-19 (1 ng/g/day) reduced aortic arch and root plaque areas by 70.1% and 32.1%, respectively, in LDLR^-/- mice. At 10 ng/g/day, rIL-19 completely eliminated atherosclerotic plaques. There were no sex differences in the effects of rIL-19 on atherosclerotic mice. Thus, low-dose rIL-19 is an effective antiatherosclerotic agent, in addition to its efficacy in intimal hyperplasia, spinal cord injury, stroke, and multiple sclerosis. We propose that IL-19 is a promising biomarker and target for the diagnosis and treatment of atherosclerosis. This review considers the role and mechanism of action of IL-19 in atherosclerosis and discusses whether IL-19 is a potential therapeutic target for this condition.

项与 IFM-2427 相关的新闻（医药）

2024-03-13

·Pharma Manufacturing

Novartis buys IFM unit, picking up STING inhibitors

Novartis has exercised its option to acquire all the outstanding capital stock of IFM Due, a subsidiary of Boston-based IFM Therapeutics. IFM Due and Novartis entered into an option and collaboration agreement back in September 2019 . Now, per the deal, IFM will receive $90 million upfront and will be eligible for up to $745 million in milestone payments, adding up to $835 million in total consideration. IFM Due was launched in February 2019, with a focus on developing small molecules that inhibit the cGAS-STING pathway. The recent acquisition provides Novartis with full rights to IFM Due’s portfolio of STING antagonists, which have the potential to treat an array of serious inflammation-driven diseases characterized by excessive interferon and other pro-inflammatory cytokine signaling. This is Novartis' second acquisition of an IFM Therapeutics subsidiary.In April 2019 Novartis paid $310 million upfront for subsidiary IFM Tre, shortly after Tre had dosed an initial subject with its first-in-class NLRP3 antagonist, IFM-2427. The molecule was the first of Tre's three unique development candidates to enter the clinic, all of which are intended to block only the inflammation driven by the NLRP3 pathway.

并购

2019-03-28

·BioSpace

IFM Therapeutics Announces Dosing of First Subjects in Phase 1 Healthy Volunteer Study of Lead NLRP3 Antagonist, IFM-2427

Announcement marks first human trial for an NLRP3 antagonist BOSTON, March 28, 2019 /PRNewswire/ -- IFM Therapeutics (IFM), a privately held biopharmaceutical company focused on developing therapies that modulate novel targets in the innate immune system, today announced that the first subjects have been dosed in a Phase 1 healthy volunteer trial of IFM-2427. IFM-2427, the lead program from IFM's subsidiary IFM Tre, is a first-in-class systemic NLRP3 (NOD-, LRR- and pyrin domain-containing 3) antagonist that can potentially block the inflammatory responses underlying a variety of serious diseases. "Initiating this Phase 1 trial of IFM-2427 – less than a year after IFM Tre was launched – is a meaningful achievement for IFM and reflective of our team's ability to efficiently advance product candidates from discovery to clinical development," said Gary D. Glick, Ph.D., Chief Executive Officer and Co-Founder of IFM Therapeutics. "Further, this first-in-human study of a systemic NLRP3 inhibitor reinforces our leadership in innate immune system biology. We are committed to exploiting the full therapeutic potential of NLRP3 inhibition through the advancement of chemically-distinct molecules with varying mechanisms of action and across a breadth of indications." NLRP3 is an intracellular innate immune signaling receptor that allows immune cells to detect the presence of pro-inflammatory foreign or endogenous molecules that signal infection, tissue damage or metabolic derangements. These conditions trigger the assembly of a multi-protein complex called an inflammasome, which then initiates an immune response. While this response can be useful for fending off foreign pathogens, abnormal or chronic activation of the NLRP3 inflammasome is known to cause negative downstream effects and the onset and progression of numerous diseases. IFM-2427 is the first of IFM Tre's three unique development candidates to enter the clinic, all of which are intended to block only the inflammation driven by the NLRP3 pathway, leaving other immune pathways unsuppressed and free to produce inflammatory responses to confront harmful pathogens. IFM-2427 is a first-in-class small molecule designed to inhibit the activity of NLRP3 outside the central nervous system by directly binding to the protein, thereby blocking its activation that leads to the maturation of the pro-inflammatory cytokines IL-1, IL-18 along with pyroptosis, an inflammatory form of cell death. The Phase I clinical study of IFM-2427 is being carried out in up to 90 subjects and is expected to complete in the fourth quarter of 2019. About IFM Tre IFM Tre, a subsidiary of IFM Therapeutics (IFM), is a biopharmaceutical company developing a suite of small-molecule antagonists targeting inappropriate inflammatory responses of the innate immune system via the NLRP3 pathway, which is believed to underlie a variety of serious diseases. The Company is developing chemically distinct systemic, gut-directed and CNS-penetrant drug candidates to address a breadth of indications triggered by NLRP3, including metabolic, fibrotic, autoimmune, autoinflammatory, and neurodegenerative diseases. About IFM Therapeutics IFM Therapeutics (IFM) is a privately held biopharmaceutical company based in Boston, Massachusetts. The Company was founded by an international group of preeminent scientists and physicians following the sale of IFM Therapeutics, Inc (originally founded by Gary Glick and Atlas Venture) to Bristol-Myers Squibb. IFM's team has discovered and developed small molecules that modulate novel targets in the innate immune system as next-generation therapies for cancer, auto-immunity, and inflammatory disorders. In addition to IFM Tre, IFM owns and operates IFM Due, a subsidiary company launched in February 2019 that is developing small-molecule antagonists and inhibitors targeting aberrant inflammatory responses of the innate immune system triggered by the cGAS-STING pathway, which is believed to underlie a variety of serious diseases. For more information, please visit . View original content to download multimedia: SOURCE IFM Therapeutics, LLC

First in Class小分子药物

100 项与 IFM-2427 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
呼吸功能不全	临床申请	匈牙利	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	西班牙	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	印度	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	德国	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	丹麦	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	巴西	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	俄罗斯	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	墨西哥	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	临床申请	荷兰	Novartis Pharmaceuticals Corp.	2020-05-27
呼吸功能不全	药物发现	阿根廷	Novartis Pharmaceuticals Corp.	2020-05-27

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04382053 (Pubmed) 人工标引	临床2期	新型冠状病毒感染 \| 呼吸功能不全	143	SoC+IFM-2427	網淵夢網繭築齋蓋鑰遞(網壓憲顧蓋構範鏇憲衊) = 範鬱蓋艱製齋蓋鬱顧夢遞鏇衊積鹽醖鹹積鹹網 (廠鏇顧齋鏇網鑰艱艱窪, 1.06) 更多	不佳	2022-09-14
				SoC	網淵夢網繭築齋蓋鑰遞(網壓憲顧蓋構範鏇憲衊) = 構夢願糧製選蓋願遞願遞鏇衊積鹽醖鹹積鹹網 (廠鏇顧齋鏇網鑰艱艱窪, 1.05) 更多
NCT04382053 (CTgov)	临床2期	新型冠状病毒感染 \| 呼吸功能不全	143	Standard of Care (SoC)+DFV890 (DFV890 + SoC)	選衊範壓淵淵醖齋襯憲(遞繭顧顧壓顧廠鏇築蓋) = 顧構繭獵顧願鹽壓顧夢鏇夢繭遞構網憲獵蓋襯 (簾構齋構餘願簾膚鬱鑰, 糧蓋網醖艱顧選範鏇醖 ~ 願鏇艱鏇選簾艱鹽壓網) 更多	-	2021-11-30
				Standard of Care (SoC) (Standard of Care (SoC))	選衊範壓淵淵醖齋襯憲(遞繭顧顧壓顧廠鏇築蓋) = 願窪選範網衊膚構鹽築鏇夢繭遞構網憲獵蓋襯 (簾構齋構餘願簾膚鬱鑰, 淵網選積餘膚觸憲艱選 ~ 襯選構齋齋餘範製蓋鏇) 更多