Withdrawal of Tiratricol Treatment in Males With Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency): A Double-blind, Randomized, Placebo-controlled Study

This is a double-blind, randomized phase 3 multicenter placebo-controlled study in at least 16 evaluable male participants diagnosed with MCT8 deficiency. Male participants, from 4 years of age (at randomization) and having demonstrated stable maintenance treatment with tiratricol, will be randomized to receive placebo or tiratricol for 30 days or until reaching rescue criterion (serum total triiodothyronine [T3] > upper limit of normal [ULN] of the participant's normal range, for a sample collected during the 30-day Randomized Treatment Period). The research hypothesis to be tested is that, for participants in the placebo group, removal of tiratricol will lead to an increase of serum total T3 concentration, measured by liquid chromatography with tandem mass spectrometry (LC/MS/MS), above the ULN and requirement of rescue treatment with tiratricol, compared to those who continue to receive tiratricol.

开始日期2023-07-21

申办/合作机构

Rare Thyroid Therapeutics International AB

[+2]

NCT02396459 / Active, not recruiting临床2期

Tiratricol Treatment of Children With Monocarboxylate Transporter 8 Deficiency: Triac Trial II

This study will investigate the effect of treatment with tiratricol (also called Triac) in young boys (≤30 months) with MCT8 deficiency (also called the Allan-Herndon-Dudley syndrome (AHDS)). The hypothesis tested is that treatment with tiratricol will have a beneficial effect on the hypothyroid state in the brain as well as the hyperthyroid state in peripheral organs and tissues in these patients. Patients will initially be treated for 96 weeks with tiratricol, treatment effect on neurodevelopment impairment caused by hypothyroidism and peripheral thyrotoxicosis will be evaluated after 96 weeks treatment. Patients will be offered to continue on treatment for an additional 2 years.

开始日期2020-12-07

申办/合作机构

Rare Thyroid Therapeutics International AB

[+1]

NCT05911399 / AvailableN/A

Expanded Access Program for Tiratricol in Patients With Monocarboxylate Transporter 8 Deficiency Also Known as Allan-Herndon-Dudley Syndrome (AHDS)

The goal of this program is to provide expanded access (i.e., before marketing authorization) to tiratricol as treatment for patients with monocarboxylate transporter 8 deficiency (MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome [AHDS]), who in their Treating Physician's opinion, could benefit from tiratricol and meet the eligibility criteria.

开始日期-

申办/合作机构

Rare Thyroid Therapeutics International AB

[+2]

100 项与替拉曲可相关的临床结果

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100 项与替拉曲可相关的转化医学

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100 项与替拉曲可相关的专利（医药）

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512

项与替拉曲可相关的文献（医药）

2024-01-01·Chemosphere

Bisphenol A alters retinal morphology, visually guided behavior, and thyroid hormone levels in zebrafish larvae

Article

作者: Hansen, Martin ; Poulsen, Rikke ; Volz, Sina N ; Holbech, Henrik

Bisphenols are industrial chemicals that are produced in large quantities and have been detected in all parts of the environment as well as in a multitude of different organisms including humans and fish. Several bisphenols, such as bisphenol A (BPA) and bisphenol F, have been shown to disrupt endocrine systems thereby affecting development and reproduction. While numerous studies investigated the effect of bisphenols on estrogen signaling, their impact on the thyroid hormone system (THS), which is vital for neurodevelopment including sensory development, has been explored to a lesser extent. The present work selected BPA as a representative for structurally similar bisphenols and assessed its impact on the THS as well as sensory development and function in zebrafish. To this end, zebrafish were exposed to BPA until up to 8 days post fertilization (dpf) and thyroid hormone levels, eye morphology, and sensory-mediated behaviors were analyzed. Zebrafish larvae exposed to BPA showed altered retinal layering, decreased motility across varying light conditions, and a loss of responsiveness to red light. Furthermore, whole-body levels of the thyroid hormones thyroxine (T4) and 3,5-diiodothyronine (3,5-T2) were significantly decreased in 5 dpf zebrafish. Taken together, BPA disrupted THS homeostasis and compromised visual development and function, which is pivotal for the survival of fish larvae. This work underlines the necessity for ongoing research on BPA and its numerous substitutes, particularly concerning their effects on the THS and neurodevelopment, to ensure a high level of protection for the environment and human health.

2023-12-01·Archivos argentinos de pediatria

Treatment with TRIAC in pediatric patients with MCT8

Article

作者: Dujovne, Noelia ; Herzovich, Viviana ; Pérez Garrido, Natalia ; Gazek, Natalia ; Feller, Ana L ; Lazzati, Juan M ; Savransky, Andrea ; Di Palma, Isabel ; Marino, Roxana ; Ramírez, Pablo ; Vaiani, Elisa

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

2023-11-01·Antiviral research

Tiratricol inhibits yellow fever virus replication through targeting viral RNA-dependent RNA polymerase of NS5

Article

作者: Ren, Hao ; Tang, Hailin ; Zhao, Ping ; Xia, Binghui ; Qi, Zhongtian ; Xu, Zhenghao ; Luo, Zhenghan ; Wang, Jiaqi ; Qian, Xijing

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific antiviral drugs are available for treating yellow fever. Here, we report that tiratricol (triiodothyroacetic acid, TRIAC), a clinically approved drug used to treat thyroid hormone resistance syndrome (THRS), is a potent YFV inhibitor both in host cells and in animal models.An in vitro study demonstrates that TRIAC remarkably suppresses viral RNA synthesis and protein expression in a dose-dependent manner in human hepatoma cell lines (Huh-7) with an EC50 value of 2.07 μM and a CC50 value of 385.77 μM respectively. The surface plasmon resonance assay and molecular docking analysis indicate that TRIAC hinders viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5, probably through interacting with the active sites of RdRp.The inhibitory effect of TRIAC in vivo is also confirmed in 3-week old C57BL/6 mice challenged with YFV infection, from which the survival of the mice as well as lesions and infection in their tissues and serum issignificantly promoted following oral administration of TRIAC (0.2 mg/kg/day). Additionally, TRIAC shows a broad-spectrum antiviral activity against multiple flaviviruses such as TBEV, WNV,ZIKV, andJEV in vitro. Our data demonstrate that the TH analogue TRIAC is an effective anti-YFV compound and may act as a potential therapeutic candidate for the treatment of YFV infection if its clinical importance is determined in patients in future.

项与替拉曲可相关的新闻（医药）

2023-03-31

·FierceBiotech

What M&A slowdown? Buyers circle GreenLight Biosciences, Egetis Therapeutics

Both GreenLight and Egetis pointed out that they hadn't accepted an offer yet. While biotech M&A may have cooled down over the past year, no one has told GreenLight Biosciences or Egetis Therapeutics, which are both mulling takeover offers. RNA-focused GreenLight announced yesterday that it has received an offer from VC firm Fall Line Capital’s Fall Line Endurance Fund to acquire all outstanding stock of the biotech for 60 cents per share. GreenLight— which spreads itself across vaccines and therapies for humans as well as agricultural solutions—only went public via a special purpose acquisition company (SPAC) merger in February 2022. The merger agreement valued the company at $1.2 billion and GreenLight’s stock hit a high of over $12 per share in the following weeks. But it’s been dropping ever since, with a closing price Thursday of just 43 cents. Still, the biotech emphasized that no sale has been agreed yet, with the company’s board of directors due to “carefully evaluate Fall Line’s indication of interest within the context of the ongoing review of various alternatives and in consultation with any financial and legal advisors it may retain.” GreenLight ended 2022 with $68.1 million in cash and equivalents. Despite pausing its gene therapy program for sickle cell anemia and cutting 25% of staff in October 2022 to save money, the company still expects reserves to run dry by June. The biotech had already announced it was looking at a range of measures to eke out its runway, including “further management of program spending, additional platform licensing collaborations and potential further financing activities.” Even with human health ambitions now limited to preclinical vaccine candidates for pan-sarbecovirus and shingles, as well as a cancer vaccine collab with EpiVax, it’s not surprising the company is open to external offers. Less is known about Egetis’ offer. The biotech released a concise note yesterday responding to “existing rumors” by confirming that the company “has ongoing discussions with certain external parties regarding a potential acquisition.” Again, Egetis was keen to stress that no offer has yet been agreed. The Swedish company’s lead product is Emcitate, which is in phase 2 trials for Allan-Herndon-Dudley syndrome, a rare genetic disorder that impacts a child's cognition, mobility and overall health and for which there is currently no available treatment. Egetis plans to submit a request for EU approval in the second quarter of the year based on existing clinical data.

疫苗并购临床2期

2021-02-27

·药融圈

40款新药研发有新进展，国产康希诺新冠疫苗重磅来袭！感染领域再发力，涉及康希诺、康泰、瑞科、默沙东、拜耳等！

▲速抢免费参会名额 | 大湾区(广州)生物医药创新者峰会导语根据公开资料不完全统计，药融云为大家检测到了2021年2月16日至2021年2月22日的全球新药重大研发进展40条。其中涉及药物上市2条，药物提交上市申请4条，临床重大进展33条，2款药物研究终止。 9款治疗“新型肺炎冠状病毒感染(COVID-19)”的药物研发阶段发生重大进展，康希诺和拜耳提交上市申请。根据《疫苗管理法》、《药品管理法》相关规定，新冠疫苗按照药品特别审批程序，进行应急审评审批，而且新冠疫苗的研发过程中企业就与药审中心进行滚动资料提交，因此从递交上市申请到获批上市用时非常短，预计康希诺Ad5-nCoV近期也会加快获批上市。康希诺的新冠疫苗上市申请获受理，康希诺生物B盘中大涨逾10%。数据来源：东方财富网表1 40款药物基本信息数据来源：药融云全球药物研发数据库据统计，40款药物的治疗领域主要是感染、肿瘤等。据统计，40款药物的适应症主要是新型肺炎冠状病毒感染(COVID-19)。表2 40款药物适应症(TOP10) 数据来源：药融云全球药物研发数据库上市药物生物药evinacumab（依维苏单抗）和rVSV-EBOV获批上市。 01 evinacumab（依维苏单抗）近日，FDA批准再生元研发的evinacumab上市，用于治疗纯合子家族性高胆固醇血症（HoFH）。人源化单克隆抗体evinacumab是一种血管生成素相关蛋白-3（ANGPTL3）抑制剂，曾获“突破性疗法（2017年）、快速通道、孤儿药、儿科用药研究计划、优先审评（2020年）”资格认定。 evinacumab之所以可以降低HoFH患者的胆固醇含量，是因为它主要靶向ANGPTL3，可以有效抑制蛋白脂肪酶和内皮质酶，并且可以在脂蛋白的代谢中起到关键作用。由于evinacumab的独特靶点和作用机制，再生元还正在进行evinacumab 治疗“顽固型高胆固醇血症”和“重度高甘油三酯血症”的二期临床试验。 evinacumab的获批是基于一项评估evinacumab治疗HoFH的疗效性和安全性试验。此项试验，65例HoFH患者被随机分为两组：evinacumab组（43例）和安慰剂组（22例）。在基线时，evinacumab组和安慰剂组患者的基线平均低密度脂蛋白胆固醇（LDL-C）水平相似，分别为259.5mg/dl和246.5 mg/dl。evinacumab组患者每4周静脉注射evinacumab 15mg/kg，为期24周。主要终点为基线至24周时LDL-C的降低。研究显示，在第24周时，evinacumab组患者的LDL-C水平降低了47.1%，安慰剂组则增加了1.9%（LS平均差异为-49.0%，P＜0.0001）。 evinacumab的获批对于HoFH患者是一个分水岭，为HoFH患者提供了新的治疗选择。根据药融云全球药物研发数据库预测，evinacumab未来5年的销售额有可能会逐年增加，预计今年的销售额可达到0.12亿万美元，2025年或可达到1亿美元。 02 rVSV-EBOV 近日，默沙东研发的治疗“埃博拉病毒传染”的糖蛋白rVSV-EBOV在多个国家/地区上市，曾获“加速批准、突破性疗法、优先审评、EMA优先药物”。rVSV-EBOV最初由加拿大微生物实验室公共卫生署研发，之后授予默沙东研发和市场化权利。根据药融云全球药物研发数据库预测，rVSV-EBOV未来5年的销售额有可能会逐年增加，预计今年的销售额可达到0.3亿万美元，2025年或可达到1亿美元。提交上市申请的药物 Ad5-nCoV、omalizumab biosimilar（奥马珠单抗类似药）、SARS-CoV-2 mRNA vaccine和ARI-0001提交上市申请。 01 Ad5-nCoV 康希诺生物与中国人民解放军军事医学科学院生物工程研究所合作研发的COVID19刺突糖蛋白调节剂Ad5-nCoV提交上市申请，用于治疗“新型肺炎冠状病毒感染(COVID-19)”，曾获“紧急使用授权”资格。 Ad5-nCoV的Ⅲ期临床试验结果显示：在单针接种疫苗28天后，疫苗对所有症状的总体保护效力为65.28%；在单针接种疫苗14天后，疫苗对所有症状总体保护效力为68.83%。疫苗对重症的保护效力分别为：单针接种疫苗28天后为90.07%；单针接种疫苗14天后为95.47%。康希诺生物新冠疫苗接种一针即可提供保护力。储运条件也相对便捷，从目前的研究结果来看，在2-8℃ 条件下可稳定保存至少3个月，在25℃条件下可稳定保存至少2个月，在37℃ 条件下可稳定保存至少3周。目前，国内已经有两款疫苗获批附条件上市，均为灭活疫苗，分别来自国药集团中国生物和北京科兴。如果本次康希诺生物最终顺利获批，则意味着将成为国内获得附条件上市的第三款疫苗，同时也是国内获批的首款腺病毒载体新冠疫苗。 02 omalizumab biosimilar（奥马珠单抗类似药）人源化单克隆抗体奥马珠单抗类似药是一款治疗哮喘的免疫球蛋白E拮抗剂。 03 SARS-CoV-2 mRNA vaccine 拜耳研发的SARS-CoV-2 mRNA vaccine 是一款治疗新型肺炎冠状病毒感染(COVID-19)和SARS病毒感染的COVID19刺突糖蛋白调节剂。 04 ARI-0001 B淋巴细胞抗原CD19调节剂ARI-0001是一款治疗“急性淋巴细胞白血病、慢性淋巴细胞白血病、非霍奇金淋巴瘤”的嵌合抗原受体T细胞疗法，此次提交上市申请的适应症是“急性淋巴细胞白血病”。进入临床三期的药物 glofitamab、upamostat、Mim-8、tiratricol（替拉曲考）和posoleucel进入临床三期。 01 glofitamab 罗氏研发的glofitamab是双特异性T细胞衔接子抗体，用于治疗“B淋巴细胞瘤、弥漫性大B细胞淋巴瘤、滤泡中心淋巴瘤、多发性骨髓瘤、非霍奇金淋巴瘤”。此次进入临床三期的适应症是“弥漫性大B细胞淋巴瘤”。 glofitamab是靶向CD20和CD3的双特异性抗体，靶向B细胞表面的CD20和T细胞表面的CD3。其中CD20位点使用的是二代人源化CD20单抗奥妥珠单抗的位点。基于一种新颖的结构形式，称之为“ 2：1”，指的是具有两个与CD20结合的“ Fab”区域和一个与CD3结合的“ Fab”区域。这种结构的优势在于glofitamab能够与B细胞表面CD20的结合性更高。即使肿瘤细胞表达CD20含量较低，glofitamab也可以找到肿瘤细胞发挥作用。CD20和CD3首尾相连的结构也可以诱导快速T细胞活化、增殖、细胞因子释放，导致靶细胞裂解。而且“ 2：1”的结构形式也能够使glofitamab与其他抗CD20抗体联用，为后续研发联合治疗方案提供可能性。 02 upamostat RedHill Biopharma Ltd研发的upamostat是一种新型且有效的胰蛋白酶、丝氨酸蛋白酶抑制剂，靶向参与为病毒侵入目标细胞准备刺突蛋白的人类细胞因子，有望有效对抗新出现的带刺突蛋白突变的病毒变种，用于治疗“乳腺肿瘤、新型肺炎冠状病毒感染(COVID-19)、胃肠道炎症、胃肠道肿瘤、胰腺肿瘤”，曾获“孤儿药”资格认定。此次进入临床三期的适应症是“新型肺炎冠状病毒感染(COVID-19)”。近日，RedHill Biopharma Ltd宣布，其研发的口服胶囊upamostat在美国启动三期临床试验，该实验旨在评估upamostat治疗轻症新冠肺炎患者的疗效。 03 Mim-8 诺和诺德研发的免疫球蛋白G同型抗体Mim-8，是一种凝血因子IX和X拮抗剂，用于治疗“凝血因子VIII缺乏症”。 04 tiratricol（替拉曲考） Rare Thyroid Therapeutics International AB研发的tiratricol用于治疗“X连锁遗传病”，甲状腺激素受体激动剂，曾获“孤儿药、罕见儿科疾病用药”资格认定。 05 posoleucel AlloVir研发的posoleucel，是一种T淋巴细胞疗法，用于治疗“腺病毒感染、BK病毒感染、膀胱炎、巨细胞病毒感染、EB病毒感染、造血干细胞移植、疱疹病毒6型感染、多瘤病毒感染”，曾获“孤儿药、EMA优先药物、再生医学先进疗法”资格认定。此次进入临床二期的适应症是“巨细胞病毒感染、腺病毒感染、BK病毒感染、EB病毒感染、多瘤病毒感染、疱疹病毒6型感染”。版权声明：本文转自药融云，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看

疫苗抗体孤儿药合作免疫疗法

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KEGG	Wiki	ATC	Drug Bank
D07214	替拉曲可	D11AX08 H03AA04	DB03604

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
Allan-Herndon-Dudley综合征	申请上市	-	Egetis Therapeutics AB	-

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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


NCT02060474 (Pubmed) 人工标引	临床2期	Allan-Herndon-Dudley综合征	46	Triac	繭選觸顧鬱襯網鬱廠繭(蓋襯鹽醖構膚壓積糧築) = (transiently increased perspiration or irritability) occurred in six (13%) patients 淵遞夢糧鹹願簾糧鹽餘 (壓糧襯壓遞淵積壓選願 ) 更多	积极	2019-09-01