(Talfirastide) - 药物靶点：Mas receptor_在研适应症：缺血性卒中，DMD相关的扩张型心肌病，杜氏肌营养不良症_专利_临床

A Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury (TBI)

The goal of this clinical trial is to test the safety of the drug Angiotensin (1-7) and learn whether it works well as a treatment in people who have suffered a moderate to severe traumatic brain injury (TBI).
The main questions this trial aims to answer are:
Is Angiotensin (1-7) safe?
Does Angiotensin (1-7) improve mental functioning and reduce physical signs of brain damage in people who have suffered a moderate to severe TBI?
Participants will:
Complete 21 days of study treatment consisting of a once-daily injection.
Provide blood samples.
Undergo two magnetic resonance imaging (MRI) scans of the brain.
Complete specific tasks and questionnaires that allow researchers to evaluate the participant's brain and psychological functioning.
Researchers will compare three groups: two groups that receive different doses of Angiotensin (1-7) and one group that receives a look-alike treatment with no active drug. This will allow researchers to see if the drug has any negative effects and whether it improves mental functioning and physical signs of brain damage after a TBI.

开始日期2024-03-01

申办/合作机构

University of Arizona

[+1]

NCT06135103 / Recruiting临床2期

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Hybrid Decentralized Study to Evaluate the Safety and Efficacy of Daily Subcutaneous (SC) Injection of TXA127 in Post-ischemic Stroke Patients

This is a 50-patient, Phase 2, double-blind, randomized, placebo-controlled, hybrid decentralized study to evaluate the safety and efficacy of daily subcutaneous (SC) injection of TXA127 in post-ischemic stroke patients. Subjects will receive either TXA127 0.5mg/kg or placebo for 12 weeks started 6 to 24 months post ischemic stroke, and they will have a 12 week follow up visit after treatment has ended. The primary efficacy outcome measure is individual patient absolute change from baseline in motor and sensory functions as measured by the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) 12 weeks after start of treatment.

开始日期2023-11-26

申办/合作机构

Constant Therapeutics LLC

NCT06013839 / Recruiting临床2期

A Phase 2, Single-Arm, Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of TXA127/Angiotensin [1-7] in Non-Ambulant Patients With Duchenne Muscular Dystrophy (DMD) Cardiomyopathy Who Are Receiving Systemic Glucocorticoids

This open-label, single-arm multi-center study studying the safety and efficacy of TXA127 on non-ambulant patients with DMD Cardiomyopathy will comprise of two phases:
6-month open-label treatment phase: Male DMD patients with documented cardiomyopathy, will receive a daily subcutaneous injection of TXA127 0.5 mg/kg. Treatment will be provided for 6 months. Treatment safety will be assessed by collection and review of AEs, vital signs, ECGs, physical examinations, PFTs, and laboratory parameters on Day 1, Month 1, and Month 6. Ejection Fraction, upper extremity strength and biomarker levels will be assessed at these study visits as well. In addition, an abbreviated safety visit will be conducted at Month 3.
12-month optional extension phase: Patients will continue the same study drug regime for an additional 12 months. The primary objective of this phase is to obtain long-term safety data. Efficacy data will also be collected. Safety, efficacy, and exploratory biomarkers will be assessed at Month 12 and Month 18, using the same methods as in the treatment phase. In addition, abbreviated safety visits will be conducted at Month 9 and Month 15.

开始日期2023-08-31

申办/合作机构

Constant Therapeutics LLC

100 项与 Talfirastide 相关的临床结果

登录后查看更多信息

100 项与 Talfirastide 相关的转化医学

登录后查看更多信息

100 项与 Talfirastide 相关的专利（医药）

登录后查看更多信息

975

项与 Talfirastide 相关的文献（医药）

2024-01-02·The Physician and sportsmedicine

Effects of oral HPΒCD-angiotensin-(1-7) supplementation on recreational mountain bike athletes: a crossover study

Article

作者: Motta-Santos, Daisy ; Cruz de Oliveira, Emerson ; Coelho, Daniel Barbosa ; Lima-Silva, Adriano Eduardo ; de Assis Dias Martins-Júnior, Francisco ; Becker, Lenice Kappes ; Silva de Moura, Samara ; Augusto Souza Dos Santos, Robson ; Boari, Daniel

BACKGROUND:

Supplementation with Angiotensin-(1-7) [(Ang-1-7)] has received considerable attention due to its possible ergogenic effects on physical performance. The effects of a single dose of Ang-(1-7) on the performance of mountain bike (MTB) athletes during progressive load tests performed until the onset of voluntary fatigue have previously been demonstrated. This study tested the effects of Ang-(1-7) in two different exercise protocols with different metabolic demands: aerobic (time trial) and anaerobic (repeated sprint).

METHODS:

Twenty one male recreational athletes were given capsules containing an oral formulation of HPβCD-Ang-(1-7) (0.8 mg) and HPβCD-placebo (only HPβCD) over a 7-day interval; a double-blind randomized crossover design was used. Physical performance was examined using two protocols: a 20-km cycling time trial or 4 × 30-s repeated all-out sprints on a leg cycle ergometer. Data were collected before and after physical tests to assess fatigue parameters, and included lactate levels, and muscle activation during the sprint protocol as evaluated by electromyography (EMG); cardiovascular parameters: diastolic and systolic blood pressure and heart rate; and performance parameters, time to complete (time trial), maximum power and mean power (repeated sprint).

RESULTS:

Supplementation with an oral formulation of HPβCD-Ang-(1-7) reduced basal plasma lactate levels and promoted the maintenance of plasma glucose levels after repeated sprints. Supplementation with HPβCD-Ang-(1-7) also increased baseline plasma nitrite levels and reduced resting diastolic blood pressure in a time trial protocol. HPβCD-Ang-(1-7) had no effect on the time trial or repeat sprint performance, or on the EMG recordings of the vastus lateralis and vastus medialis.

CONCLUSIONS:

Supplementation with HPβCD-Ang-(1-7) did not improve physical performance in time trial or in repeated sprints; however, it promoted the maintenance of plasma glucose and lactate levels after the sprint protocol and at rest, respectively. In addition, HPβCD-Ang-(1-7) also increased resting plasma nitrite levels and reduced diastolic blood pressure in the time trial protocol.

TRIAL REGISTRATION:

RBR-2nbmpbc, registered January 6th, 2023. The study was prospectively registered.

2024-01-01·Cell biochemistry and function

Targeting PI3K/p‐Akt/eNOS, Nrf2/HO‐1, and NF‐κB/p53 signaling pathways by angiotensin 1–7 protects against liver injury induced by ischemia–reperfusion in rats

Article

作者: Ali, Fatma Farrag ; Hussein, Youssef ; Ibrahim, Manar Fouli Gaber ; Mohammed, Mostafa Mourad

Abstract:

The liver is an important organ, and hepatic ischemia–reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and mortality. Thus, our study aimed to investigate the effect of targeting PI3K/p‐Akt/eNOS (phosphoinositide 3‐kinase/phospho‐protein kinase B/endothelial nitric oxide synthase), Nrf2/HO‐1 (nuclear factor‐erythroid 2‐related factor‐2/heme oxygenase‐1), and NF‐κB/p53 (nuclear factor‐κB/tumor protein 53) signaling pathways by using angiotensin (1–7) [ang‐(1–7)] against hepatic injury induced by IR. Thirty‐two male rats were included in sham group, ang‐(1–7)‐treated group, hepatic IR group, and hepatic IR group treated with ang‐(1–7). The levels of hepatic ang‐(1–7), angiotensin II (Ang II), angiotensin‐converting enzyme 2 (ACE2), HO‐1, malondialdehyde (MDA), PI3K, and p‐Akt were assessed. The expressions of eNOS and B‐cell leukemia/lymphoma‐2 (BCL‐2) in the liver were determined. Histological assessment and immunohistochemical expression of NF‐κB, p53, and Nrf2 were carried out. The levels of reduced glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) in serum were estimated. Results showed that administration of ang‐(1–7) to hepatic IR rats led to significant amelioration of hepatic damage through a histological evaluation that was associated with significant upregulation of the expressions of PI3K/p‐Akt/eNOS and Nrf2/HO‐1 with downregulation of NF‐κB/p53 signaling pathways. In conclusion, PI3K/p‐Akt/eNOS and Nrf2/HO‐1 signaling pathways are involved in the protective effects of ang‐(1–7) against hepatic damage induced by IR. Therefore, ang‐(1–7) can be used to prevent hepatic IR, which occurs in certain conditions such as liver transplantation, hemorrhagic shock, and severe infection.

2024-01-01·Current diabetes reviews

The Counteracting Effects of Ang II and Ang-(1-7) on the Function and Growth of Insulin-secreting NIT-1 Cells

Article

作者: Xu, Mingtong ; Feng, Weilian ; Wan, Yan ; Chai, Jiani ; Wang, Xiaoyun ; Lin, Xiuhong ; Li, Feng

Introduction::

China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet β-cells remains unclear. The possible role of Angiotensin-(1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated.

Objectives::

To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet β cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma.

Methods::

NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated.

Results::

Ang II significantly reduced insulin-stimulated IR-β-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR).

Conclusion::

Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.

2

项与 Talfirastide 相关的新闻（医药）

2024-03-04

·PRNewswire

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Duchenne Muscular Dystrophy-Associated Cardiomyopathy

BOSTON, March 4, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient was dosed March 3, 2024, in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for Duchenne Muscular Dystrophy-associated (DMD-associated) Cardiomyopathy. The phase 2 trial is an open-label, multi-center trial designed to evaluate the safety and efficacy in non-ambulatory patients with DMD-associated Cardiomyopathy who are 16 years and older and who are receiving systemic glucocorticoids. Patients will receive 6 months of treatment and have the option to enter a 12-month extension study. The study is being conducted in Israel at Sheba Medical Center and Hadassah Medical Center and is expected to enroll 10 patients. "This is a significant milestone for Constant and for the DMD community," said Rick Franklin, CEO of Constant Therapeutics. "There are few treatments for DMD patients with cardiomyopathy, and heart failure is a leading cause of death in this disease. We are excited to initiate this carefully designed trial, and we look forward to sharing the data with the DMD community upon completion of the trial." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in cardiac dysfunction, TXA127 has shown therapeutic activity in animal models of chronic stroke, Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

临床2期

2024-01-09

·PRNewswire

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Ischemic Stroke Recovery

BOSTON, Jan. 9, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient has been dosed in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for ischemic stroke recovery. The phase 2 trial is a randomized, placebo-controlled, double-blind, hybrid decentralized study designed to evaluate the safety and efficacy in ischemic stroke patients who are 18 to 85 years old and who are 6 to 24 months post stroke event. Patients will receive 3 months of treatment. The study is being conducted in Israel at Sheba Medical Center in collaboration with Sabar Health for the home visits, and it is expected to enroll 50 patients. "There are no drugs available to treat chronic stroke, but the design and logistics of clinical trials in these patients is particularly difficult. We are fortunate to have been able to put together the infrastructure needed, with the participation of Sabar Health and Sheba Medical Center. This unique combination will allow us to test TXA127 for this important unmet medical need," said Rick Franklin, CEO of Constant Therapeutics." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in ischemic stroke, TXA127 has shown therapeutic activity in animal models Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

临床2期

100 项与 Talfirastide 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11720

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床3期	美国	National Institutes of Health	2021-07-15
新型冠状病毒感染	临床3期	美国	National Heart, Lung & Blood Institute	2021-07-15
缺血性卒中	临床2期	以色列	Constant Therapeutics LLC	2023-11-26
DMD相关的扩张型心肌病	临床2期	以色列	Constant Therapeutics LLC	2023-08-31
杜氏肌营养不良症	临床2期	以色列	Constant Therapeutics LLC	2023-08-31
移植物抗宿主病	临床2期	美国	Tarix Pharmaceuticals Ltd.	2013-12-01
霍奇金淋巴瘤	临床2期	美国	Tarix Pharmaceuticals Ltd.	2010-06-01
多发性骨髓瘤	临床2期	美国	Tarix Pharmaceuticals Ltd.	2010-06-01
贫血	临床2期	美国	Tarix Pharmaceuticals Ltd.	2008-10-01
淋巴细胞减少	临床2期	美国	Tarix Pharmaceuticals Ltd.	2008-10-01

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


NCT04924660 (Pubmed)	临床2/3期	新型冠状病毒感染	-	TXA-127	選鏇鬱構壓網夢願顧選(構膚衊築鏇壓製淵糧範) = 齋鹽夢醖壓鑰鏇襯願壓衊製餘蓋鏇觸願襯窪觸 (製鏇積淵襯顧蓋鬱觸衊 )	-	2023-04-11
				TRV-027	選鏇鬱構壓網夢願顧選(構膚衊築鏇壓製淵糧範) = 鬱衊衊願築膚艱獵窪壓衊製餘蓋鏇觸願襯窪觸 (製鏇積淵襯顧蓋鬱觸衊 )
NCT04401423 (CTgov)	临床2期	新型冠状病毒感染	22	TXA127 (TXA127)	鹽顧鬱遞鑰製鹹艱鬱醖(糧窪範鹹鑰衊簾壓網膚) = 憲獵遞鹹鑰廠壓糧窪網艱窪淵簾淵鏇製範積鑰 (網鹹鹹膚願壓遞壓繭簾, 衊齋製餘簾鬱鑰觸醖構 ~ 餘襯淵願餘顧製願顧憲) 更多	-	2022-07-27
				Placebo (Placebo)	鹽顧鬱遞鑰製鹹艱鬱醖(糧窪範鹹鑰衊簾壓網膚) = 獵鑰窪廠鹽鬱襯築窪鏇艱窪淵簾淵鏇製範積鑰 (網鹹鹹膚願壓遞壓繭簾, 夢繭積鑰網艱壓憲憲鑰 ~ 鹽網築膚艱廠選餘鏇壓) 更多
EULAR2017	N/A	关节炎	16	Sterile saline	夢獵膚鹹繭鑰鹽鹹製繭(夢鹹餘鹽範鏇糧餘廠蓋) = 網願糧網膚廠範積壓選鬱艱餘築鬱選構夢選鹽 (醖艱膚窪範淵願廠廠鹽 ) 更多	-	2017-06-14
				AT 1-7 (576 μg/kg/day)	夢獵膚鹹繭鑰鹽鹹製繭(夢鹹餘鹽範鏇糧餘廠蓋) = 鏇繭構網艱襯衊壓顧憲鬱艱餘築鬱選構夢選鹽 (醖艱膚窪範淵願廠廠鹽 ) 更多
FP180 (ERA2015)	N/A	肾脏疾病	-	ANGIOTENSIN (1-7)	襯遞餘鏇襯襯糧獵願願(選鏇鹹膚鏇簾淵襯廠襯) = 遞糧艱蓋積簾鏇艱憲鏇鏇構糧蓋淵網糧糧醖鹹 (選網顧願襯鹹顧範選構 )	积极	2015-05-21
				Ang (1-7) treated UUO Rats	襯遞餘鏇襯襯糧獵願願(選鏇鹹膚鏇簾淵襯廠襯) = 製廠顧襯壓淵簾蓋艱簾鏇構糧蓋淵網糧糧醖鹹 (選網顧願襯鹹顧範選構 )
ISC2014	N/A	脑卒中	24	dH2O	鏇範願淵餘選遞鑰齋衊(夢壓獵繭獵衊餘窪網鹽) = 壓遞製淵選築積鑰願獵遞夢範襯糧膚繭範觸願 (蓋糧構齋獵製襯鏇壓窪 )	积极	2014-02-01
				HPβCD/Ang-(1-7)	鏇範願淵餘選遞鑰齋衊(夢壓獵繭獵衊餘窪網鹽) = 鬱簾繭醖顧網選繭鏇夢遞夢範襯糧膚繭範觸願 (蓋糧構齋獵製襯鏇壓窪 )
NCT01553539 (CTgov)	临床2期	肉瘤 \| 骨癌 \| 软骨肉瘤 ... 更多	20	laboratory biomarker analysis+therapeutic angiotensin-(1-7)	遞簾糧鏇醖衊顧憲鏇蓋(齋獵顧網艱獵艱衊窪糧) = 襯襯簾醖蓋遞繭蓋獵鑰製願範齋餘積選衊淵簾 (觸鑰鏇糧選獵憲廠糧選, 獵範鑰窪糧選醖糧艱顧 ~ 醖觸艱觸鑰構鹹齋製構) 更多	-	2014-01-30
NCT00771810 (CTgov)	临床2期	淋巴细胞减少 \| 血小板减少症 \| 贫血 ... 更多	34	Placebo (Placebo)	艱襯獵膚觸範鹽夢遞廠(襯餘鹽淵製鹽醖廠鹹築) = 廠願繭廠遞鹹蓋願鏇構遞糧膚願顧觸夢遞遞築 (繭積膚壓襯憲鏇網範鹹, 築願顧觸齋蓋壓膚積製 ~ 艱膚廠襯鹽膚窪衊範醖) 更多	-	2013-06-07
				TXA127 (TXA127 100 ug/kg)	艱襯獵膚觸範鹽夢遞廠(襯餘鹽淵製鹽醖廠鹹築) = 廠獵餘鑰網衊鏇壓鑰鬱遞糧膚願顧觸夢遞遞築 (繭積膚壓襯憲鏇網範鹹, 簾憲鹽糧鏇獵網糧廠選 ~ 窪鹹廠遞築壓積積繭製) 更多
ARVO2005	N/A	-	-	Angiotensin (1-7)	壓範廠餘餘艱衊蓋衊網(繭窪簾鏇願糧壓餘遞築) = 膚積繭鬱膚壓顧醖觸鏇憲顧製夢遞鏇範蓋鹽壓 (鑰鏇夢繭範鑰範遞壓遞 )	-	2005-05-01