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更新于：2025-08-16
TD-0903
更新于：2025-08-16
概要
基本信息
药物类型 小分子化药 |
别名 Nezulcitinib、TD-0903、THRX-136377 |
作用方式 抑制剂 |
作用机制 JAK1抑制剂(酪氨酸蛋白激酶JAK1抑制剂)、JAK2抑制剂(酪氨酸蛋白激酶JAK2抑制剂)、JAK3抑制剂(酪氨酸蛋白激酶JAK3抑制剂) |
治疗领域 |
在研适应症 |
非在研机构- |
权益机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C30H37N7O2 |
InChIKeyVQIIUJSNIKEMCK-MHZLTWQESA-N |
CAS号2412496-23-0 |
关联
3
项与 TD-0903 相关的临床试验NCT05091723
Phase 1, Open-label Study to Assess the Pharmacokinetics and Safety of Inhaled Nezulcitinib (TD-0903) Administered in the Setting of Supplemental Oxygenation Scenarios in Healthy Participants
NCT04402866
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19
NCT04350736
A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19
100 项与 TD-0903 相关的临床结果
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100 项与 TD-0903 相关的转化医学
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100 项与 TD-0903 相关的专利（医药）
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6
项与 TD-0903 相关的文献（医药）2023-07-01BMJ open respiratory research
Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial
Article
作者: Saggar, Rajeev ; Thompson, Corbin G ; Bogus, Maxim ; Nguyen, Tuan ; Singh, Dave ; Lombardi, David A ; Belperio, John ; Woo, Jacky ; Bourdet, David L ; Haumann, Brett ; Kaufman, Elad ; Pfeifer, Nathan D ; Moskalenko, Valentyn ; Moran, Edmund J
Background:
The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.
Methods:
Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18–80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint.
Results:
Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile.
Conclusions:
Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.
2022-04-01Journal for immunotherapy of cancer2区 · 医学
JAK inhibitors and COVID-19
2区 · 医学
ReviewOA
作者: Langmuir, Peter ; Guglielmelli, Paola ; Constantinescu, Stefan N ; Levy, Gabriel
During SARS-CoV-2 infection, the innate immune response can be inhibited or delayed, and the subsequent persistent viral replication can induce emergency signals that may culminate in a cytokine storm contributing to the severe evolution of COVID-19. Cytokines are key regulators of the immune response and virus clearance, and, as such, are linked to the—possibly altered—response to the SARS-CoV-2. They act via a family of more than 40 transmembrane receptors that are coupled to one or several of the 4 Janus kinases (JAKs) coded by the human genome, namely JAK1, JAK2, JAK3, and TYK2. Once activated, JAKs act on pathways for either survival, proliferation, differentiation, immune regulation or, in the case of type I interferons, antiviral and antiproliferative effects. Studies of graft-versus-host and systemic rheumatic diseases indicated that JAK inhibitors (JAKi) exert immunosuppressive effects that are non-redundant with those of corticotherapy. Therefore, they hold the potential to cut-off pathological reactions in COVID-19. Significant clinical experience already exists with several JAKi in COVID-19, such as baricitinib, ruxolitinib, tofacitinib, and nezulcitinib, which were suggested by a meta-analysis (Patouliaset al.) to exert a benefit in terms of risk reduction concerning major outcomes when added to standard of care in patients with COVID-19. Yet, only baricitinib is recommended in first line for severe COVID-19 treatment by the WHO, as it is the only JAKi that has proven efficient to reduce mortality in individual randomized clinical trials (RCT), especially the Adaptive COVID-19 Treatment Trial (ACTT-2) and COV-BARRIER phase 3 trials. As for secondary effects of JAKi treatment, the main caution with baricitinib consists in the induced immunosuppression as long-term side effects should not be an issue in patients treated for COVID-19.We discuss whether a class effect of JAKi may be emerging in COVID-19 treatment, although at the moment the convincing data are for baricitinib only. Given the key role of JAK1 in both type I IFN action and signaling by cytokines involved in pathogenic effects, establishing the precise timing of treatment will be very important in future trials, along with the control of viral replication by associating antiviral molecules.
2021-11-01Clinical rheumatology3区 · 医学
Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials
3区 · 医学
Article
作者: Patoulias, Dimitrios ; Karagiannis, Asterios ; Papadopoulos, Christodoulos ; Doumas, Michael
Coronavirus disease-2019 (COVID-19) represents a global public health nightmare. The "cytokine storm," the most prominent underlying pathophysiologic mechanism of this disease, can theoretically be targeted at several stages. Janus kinase (JAK) inhibitors constitute a drug class that could ameliorate the inflammatory response and enhance antibody production. Herein, we aimed to evaluate the efficacy of JAK inhibitors in patients with COVID-19, performing the most updated relevant meta-analysis. We searched two major databases for randomized controlled trials (RCTs) enrolling adult patients with documented COVID-19 in the in-hospital setting, assigned either to JAK inhibitor treatment plus standard of care or standard of care alone. We set as primary efficacy outcome the endpoint of COVID-19 death on day 28 and as secondary efficacy composite outcome that of mechanical ventilation or initiation of extracorporeal membrane oxygenation (ECMO). We finally pooled data of interest from 4 RCTs in a total of 1338 subjects with documented COVID-19 infection, utilizing the following JAK inhibitors: baricitinib, ruxolitinib, tofacitinib, and nezulcitinib. Treatment with JAK inhibitor compared to control resulted in a significant reduction in the risk for COVID-19 death by 43%, while it also led to a significant decrease in the risk for mechanical ventilation or ECMO initiation by 36%. Herein, we demonstrate a clear benefit with JAK inhibitors added to standard of care in patients with COVID-19 in terms of risk reduction concerning major outcomes. Larger RCTs will elucidate their place in treatment armamentarium against COVID-19.
14
项与 TD-0903 相关的新闻（医药）
100 项与 TD-0903 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 纤维化 | 临床2期 | 美国 | 2022-09-05 | |
| 急性肺损伤 | 临床2期 | 美国 | 2020-06-24 | |
| 急性肺损伤 | 临床2期 | 巴西 | 2020-06-24 | |
| 急性肺损伤 | 临床2期 | 芬兰 | 2020-06-24 | |
| 急性肺损伤 | 临床2期 | 罗马尼亚 | 2020-06-24 | |
| 急性肺损伤 | 临床2期 | 乌克兰 | 2020-06-24 | |
| 急性肺损伤 | 临床2期 | 英国 | 2020-06-24 | |
| 新型冠状病毒感染 | 临床2期 | 美国 | 2020-06-24 | |
| 新型冠状病毒感染 | 临床2期 | 巴西 | 2020-06-24 | |
| 新型冠状病毒感染 | 临床2期 | 芬兰 | 2020-06-24 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 205 | Nebulised nezulcitinib 3mg | 蓋繭繭鏇餘選鹽窪鹽範(艱糧獵衊鏇構淵醖選鏇) = 窪遞鬱選鹽積鹽範鬱鏇 繭繭鏇壓構壓遞簾鏇鬱 (鹹觸膚觸顧築鹹簾膚廠 ) | - | 2023-07-01 | ||
Placebo | 蓋繭繭鏇餘選鹽窪鹽範(艱糧獵衊鏇構淵醖選鏇) = 餘襯醖糧範廠窪窪簾廠 繭繭鏇壓構壓遞簾鏇鬱 (鹹觸膚觸顧築鹹簾膚廠 ) | ||||||
临床2期 | 210 | 壓艱窪憲願遞淵膚獵製(選築選糧範醖鏇願衊觸) = 憲憲壓壓糧淵願淵蓋淵 鑰鑰鹹廠壓憲製遞構積 (製淵簾遞築繭醖鏇鑰壓 ) | 积极 | 2022-09-04 | |||
Placebo | 壓艱窪憲願遞淵膚獵製(選築選糧範醖鏇願衊觸) = 鬱選製衊糧觸衊廠襯網 鑰鑰鹹廠壓憲製遞構積 (製淵簾遞築繭醖鏇鑰壓 ) | ||||||
N/A | - | Inhaled nezulcitinib 1 mg | 艱選窪網窪願顧膚積糧(鑰膚廠齋艱範膚鏇齋艱) = the majority of treatment-emergent AEs (TEAEs) were mild and not considered related to nezulcitinib. All serious TEAEs were considered related to underlying disease; the most frequent were acute respiratory distress syndrome (Part 1) and respiratory failure (Part 2) 餘夢簾糧餘衊鹽選願蓋 (構願構築範鑰鏇網齋齋 ) | - | 2022-05-15 | ||
Inhaled nezulcitinib 3 mg | |||||||
临床2期 | 235 | placebo (Part 2: Matching Placebo) | 餘鹹廠鹽願淵膚願繭積(顧獵簾獵鬱簾廠製衊顧) = 觸鏇鏇鹹鏇糧膚築鏇鹽 網鬱壓鹹範範鑰蓋鹹遞 (糧襯夢艱夢積範壓淵衊, 餘蓋膚壓獵顧繭鹽鏇獵 ~ 鹹遞淵構鏇鏇構壓積糧) 更多 | - | 2022-03-17 | ||
(Part 2: TD-0903 - 3 mg) | 餘鹹廠鹽願淵膚願繭積(顧獵簾獵鬱簾廠製衊顧) = 糧壓築餘襯醖鑰觸壓夢 網鬱壓鹹範範鑰蓋鹹遞 (糧襯夢艱夢積範壓淵衊, 構淵願窪廠繭夢願鹹選 ~ 衊選艱鏇廠遞鹽齋衊積) 更多 | ||||||
临床1期 | 24 | 齋窪網衊壓憲製製齋築(齋觸壓遞獵襯觸窪夢糧) = 鏇簾膚襯鏇襯壓顧選膚 夢遞憲簾蓋餘範艱簾窪 (選廠築網顧餘憲襯窪選 ) | 积极 | 2021-11-01 | |||
Placebo | 齋窪網衊壓憲製製齋築(齋觸壓遞獵襯觸窪夢糧) = 顧襯餘夢製齋糧網築鬱 夢遞憲簾蓋餘範艱簾窪 (選廠築網顧餘憲襯窪選 ) | ||||||
临床2期 | 200 | 製繭築簾鹹製夢顧繭選(鑰衊積簾艱鹹襯顧構顧) = 製艱範艱淵淵窪網憲遞 鹹鹽繭憲艱鏇膚觸顧觸 (廠憲積顧獵膚壓齋繭艱 ) 更多 | 不佳 | 2021-06-21 | |||
Placebo | 製繭築簾鹹製夢顧繭選(鑰衊積簾艱鹹襯顧構顧) = 襯鬱選顧鹹膚積蓋窪膚 鹹鹽繭憲艱鏇膚觸顧觸 (廠憲積顧獵膚壓齋繭艱 ) 更多 |
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