主要目的，A部分加B部分（诱导治疗）：评估不同剂量的SAR443122在中重度UC受试者中的疗效。次要目的，A部分和B部分（诱导治疗）：1）评估SAR443122对UC受试者内镜下改善的影响。2）评估SAR443122对UC受试者的临床缓解和临床应答的影响。3）评估SAR443122对UC受试者组织学改善的影响。4）评估SAR443122对UC受试者组织学-内镜黏膜改善（HEMI）的影响。5）评估SAR443122对疾病特定生活质量的影响。6）评估SAR443122对患者报告的溃疡性结肠炎体征和症状的影响；评估SAR443122在UC受试者中的药代动力学；评估中重度UC受试者接受52周SAR443122治疗的安全性和耐受性。

开始日期2023-07-19

申办/合作机构

Creapharm Clinical Supplies SAS

[+4]

CTRI/2023/06/053613 / Not yet recruiting临床2期

A randomized, double-blind, placebo controlled, dose finding study to assess the efficacy and safety of SAR443122 in adult patients with moderate to severe ulcerative colitis - RESOLUTE

开始日期2023-06-20

申办/合作机构

Sanofi-Aventis Recherche et Développement SA

NCT05588843 / Recruiting临床2期

A Randomized, Double-blind, Placebo Controlled, Dose-finding Study to Assess the Efficacy and Safety of SAR443122 in Adult Patients With Moderate to Severe Ulcerative Colitis

This is a randomized, double-blind, placebo controlled, dose-ranging Phase 2 study. The primary objective is to evaluate the efficacy and safety of SAR443122 compared to placebo in participants with moderate to severe UC. Dose selection for further clinical development will be based on the multiple efficacy, safety and PK parameters.
The study consists of 4 parallel arms (3 dose groups of SAR443122 vs placebo) to assess the efficacy and safety of SAR443122 in participants with moderate to severe UC. All participants will receive a total of 52 weeks (a 12-week induction treatment phase and a 40-week maintenance phase) of study treatment, except if treatment should be discontinued per investigator's assessment.
At the end of the first 12 weeks of induction treatment, all participants in clinical response or remission will be offered study treatment up to 40 weeks and will continue with the same blinded treatment that was assigned. Participants who do not achieve clinical response or remission at the end of the initial 12 weeks induction treatment will roll over in an open-label treatment arm and will be treated with SAR443122 at the highest tested dose.
In addition, participants from the maintenance treatment that lose clinical efficacy at any time up to V10/Week 40 (Week 28 of maintenance) will be offered to roll over in the open-label treatment arm with SAR443122 at the highest dose.

开始日期2022-11-25

申办/合作机构

Sanofi

100 项与 Eclitasertib 相关的临床结果

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100 项与 Eclitasertib 相关的转化医学

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100 项与 Eclitasertib 相关的专利（医药）

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项与 Eclitasertib 相关的文献（医药）

2024-11-01·Bioorganic & Medicinal Chemistry Letters

Harnessing dual-mode RIPK1 ligands for cross-species anti-necroptosis inhibitor compounds

Article

作者: Bana, Péter ; Linke, Nikolett ; Éles, János ; Gábor Vass, Csaba ; Katalin Szalai, Krisztina ; Kálomista, Ildikó ; Greiner, István ; Levente Petró, József ; Hornyánszky, Gábor ; Eszter Szabó, Judit

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) has a crucial role in cell death and inflammation. A promising approach to develop novel inhibitors of RIPK1 mediated necroptosis is to mix the different binding modes of the known RIPK1 inhibitors into one molecule. Herein we report the synthesis and biological evaluation of novel mixed type inhibitors. Using Eclitasertib as a starting point, and applying our previous, published knowledge regarding cyclic malonamides, we successfully identified a library of active compounds. The active enantiomer of the most balanced and promising compound was subjected to pharmacokinetics and in vivo hypothermia study in mice.

Respiratory Research

Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study

Article

作者: Wiekowski, Maria ; Clot, Pierre-Francois ; Suratt, Benjamin T ; Farenc, Christine ; Krahnke, Tillmann ; Staudinger, Heribert ; Florian, Peter ; Terrier, Benjamin ; Patel, Naimish ; Pomponio, Robert ; Lin, Yong ; Tardat, Agnes

AbstractBackgroundTargeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19.MethodsIn this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored.ResultsGeometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49–1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia.ConclusionsEclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo.ClinicalTrials.gov identifierNCT04469621, first posted on clinicaltrials.gov on July 14, 2020.

项与 Eclitasertib 相关的新闻（医药）

2024-10-15

·Outsourcing Pharma

Sanofi abandons phase 2 trial of Denali’s multiple sclerosis candidate

The K2 trial tested oditrasertib’s safety and ability to reduce the blood levels of neurofilament light chain, a biomarker of neuronal damage in multiple sclerosis. However, the trial failed to meet its primary and undisclosed key secondary endpoints, according to a filing . Multiple sclerosis is a degenerative and progressive disorder where the immune system attacks the insulation around nerve cells, leading to the death of the cells and to increasing disability in people with the condition, which number around 2.8 million . Oditrasertib is designed to block a protein called receptor-interacting protein kinase 1 (RIPK1), which is involved in cell death. Blocking RIPK1 could make nerve cells more resistant to the pathology and slow down the disease. Denali obtained oditrasertib in 2016 when it took over the previous developer Incro Pharmaceuticals. Sanofi then got in on the action when it inked a $1 billion strategic collaboration with Denali in 2018 to develop candidates for the treatment of immunological and neurological conditions. Numerous setbacks The partnership has faced numerous obstacles in the last few years. Another of the RIPK1 inhibitors in the deal flopped in a phase 1b trial for the treatment of Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) in 2020, leading the partners to focus on oditrasertib. In February this year, however, oditrasertib failed in a phase 2 trial for the treatment of ALS and Sanofi discontinued the trial. Another RIPK1 inhibitor in the sights of the partners is eclitasertib, which cannot penetrate the central nervous system and is in phase 2 development for the treatment of ulcerative colitis. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Denali Therapeutics raised $500 million in a private placement in February this year and its main candidate, an enzyme replacement therapy to treat the rare disease mucopolysaccharidosis type II, is in a phase 2/3 trial set to complete enrollment this year. The growing prevalence of multiple sclerosis is set to drive the global market for treatments, which was worth $21.3 billion in 2023 and is projected to grow by 7.9% to $38.9 billion by 2032. Getting a RIPK1 blocker to the market is proving difficult for many players, with a candidate developed by GlaxoSmithKline showing no efficacy signs in clinical results in patients with ulcerative colitis published in 2021. Some of the most advanced RIPK1 contenders include phase 1-stage programs by China’s GenFleet Therapeutics, Roche’s U.S. company Genentech, and a compound developed by Eli Lilly and Rigel Pharmaceuticals.

临床2期上市批准临床1期并购

2024-10-10

·Endpoints

Sanofi discontinues Denali-partnered MS trial after Phase 2 failure

Sanofi is ending a Phase 2 clinical trial that’s testing a drug from Denali for multiple sclerosis, putting a stop to the development plan. Denali said in an SEC filing Thursday that Sanofi notified the company that the drug, oditrasertib, did not meet primary or key secondary endpoints in the study. The drug looked to block RIPK1, a signaling protein that when overstimulated can drive neuroinflammation and cell death, root causes of diseases like multiple sclerosis. A Sanofi spokesperson said the company has no other planned studies. The new data are the latest in a string of disappointing readouts since the collaboration got off the ground. Sanofi paid Denali $125 million upfront back in 2018 with more than $1 billion in potential milestone payments, a huge bet on the RIPK1 target that oditrasertib was aimed at. In February, oditrasertib failed a Phase 2 ALS study , after failing to improve patient symptoms as measured by the ALS Functional Rating Scale. Another drug that headlined the 2018 deal, DNL747, was fully halted in 2020 after the companies got a peek at Phase 1b data in patients with Alzheimer’s and ALS. A third asset, DNL758, is still in the middle of a Sanofi-run Phase 2 study for patients with ulcerative colitis. But the company discontinued an earlier study in October 2023 after the drug was found to not be effective in patients with cutaneous lupus erythematosus. Despite the pared-back collaboration, Denali entered the third quarter with $1.35 billion in cash, equivalents and marketable securities as of the end of June. That funding will help pay for advancing the company’s mid- to late-stage pipeline, including a potential treatment for Hunter syndrome that Denali is teeing up for an accelerated approval application. The company said last month that it had a successful meeting with the FDA about a surrogate endpoint and plans to submit the application in early 2025.

临床2期加速审批临床失败

2024-02-20

·FierceBiotech

Sanofi stumbles in HIMALAYA trial, chalking up phase 2 ALS fail in another blow to Denali alliance

Shares in Denali Therapeutics fell 7.3% to $17.02 Friday. Sanofi’s HIMALAYA adventure has ended in failure, dealing another blow to its RIPK1 collaboration with Denali Therapeutics. The phase 2 study randomized 305 people with amyotrophic lateral sclerosis (ALS) to receive SAR443820, a RIPK1 inhibitor also known as DNL788, or placebo orally twice a day. After 24 weeks, Sanofi assessed the change from baseline on an ALS severity scale, ALSFRS-R. The clinical trial also features an open-label extension designed to measure the combined assessment of the function and survival score at Week 52. In a financial filing, Denali revealed the HIMALAYA study failed to meet the ALSFRS-R primary endpoint. Sanofi will share detailed safety and efficacy results at an upcoming scientific forum. For now, the only information is that the study missed its primary endpoint. Sanofi is continuing to study SAR443820 in a phase 2 multiple sclerosis trial. That study began dosing 13 months ago, triggering a $25 million milestone payment to Denali, and finished enrolling its 174 subjects by the end of 2023. The primary completion date is September 2025, according to ClinicalTrials.gov. The multiple sclerosis study is part of a dwindling list of opportunities open to the Sanofi-Denali RIPK1 collaboration. Sanofi paid $125 million to buy into the program in 2018, 11 months after Denali raised $250 million in the biggest biotech IPO of 2017. However, the project hit an early bump in the road when the partners switched to a backup compound in response to chronic toxicity data on their lead asset. In parallel, the partners worked on another RIPK1 inhibitor that, unlike SAR443820, is designed not to penetrate the central nervous system. That drug, eclitasertib, is being studied in peripheral inflammatory diseases but has suffered setbacks. Sanofi stopped work on cutaneous lupus erythematosus last year in response to phase 2 efficacy data, although it is continuing to run a midstage study in ulcerative colitis. Other companies have shared Sanofi’s interest in RIPK1. Eli Lilly paid Rigel Pharmaceuticals $125 million for an inhibitor of the kinase in 2021 and began a phase 2 rheumatoid arthritis study last year. GSK, which previously dropped a RIPK1 cancer candidate, offloaded an asset to Boston Pharmaceuticals in 2021. Bristol Myers Squibb removed a phase 1 RIPK1 inhibitor from its pipeline last year. Shares in Denali fell 7.3% to $17.02 over the course of Friday's trading.

临床2期临床1期IPO财报

100 项与 Eclitasertib 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
皮肤红斑狼疮	临床2期	乌克兰	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	加拿大	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	美国	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	澳大利亚	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	意大利	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	匈牙利	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	捷克	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	智利	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	波兰	Sanofi	2021-04-01
皮肤红斑狼疮	临床2期	阿根廷	Sanofi	2021-04-01

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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


NCT04781816 (CLEan, CTgov)	临床2期	皮肤红斑狼疮	78	Placebo (Placebo)	鏇鑰製獵廠淵構襯簾艱(鹽糧蓋糧簾鏇糧範壓構) = 夢鏇鏇糧繭顧構餘鹹製築鑰襯築鬱醖齋醖鏇願 (憲齋獵遞憲獵網蓋網繭, 製網築獵蓋積鑰積簾繭 ~ 鏇膚夢襯願憲築蓋膚遞) 更多	-	2024-06-24
				SAR443122 (SAR443122)	鏇鑰製獵廠淵構襯簾艱(鹽糧蓋糧簾鏇糧範壓構) = 構築簾觸蓋鏇鑰築範顧築鑰襯築鬱醖齋醖鏇願 (憲齋獵遞憲獵網蓋網繭, 構繭憲蓋獵淵範鑰窪艱 ~ 願襯壓構簾積顧夢齋糧) 更多