The Efficacy of Hydroxychloroquine Combined With Levothyroxine in Euthyroid Women With Thyroid Antibody Positive and Unexplained Recurrent Pregnancy Loss：A Multicenter, Randomized Controlled Study

The goal of this clinical trial is to learn if combined treatment of levothyroxine and hydroxychloroquine would improve the live birth of euthyroid women with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss.
Researchers will compare combined treatment of levothyroxine and hydroxychloroquine to a treatment of levothyroxine alone to see if combined treatment works to improve live birth of euthyroid participants with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss.
Participants will:
* Receive combined treatment of levothyroxine and hydroxychloroquine or treatment of levothyroxine alone every day at least 8 weeks before pregnancy, and continue their treatment till the end of pregnancy.
* Visit the clinic 4 weeks and 8 weeks after their treatments, and every 12 weeks before they get pregnant for checkups and tests. During their pregnancy, they will visit the clinic before gestation of 12 weeks, and will be followed up with phone call in the second trimester and after parturition.

开始日期2024-12-01

申办/合作机构

Sun Yat-Sen Memorial Hospital

NCT06676384 / Not yet recruiting临床4期IIT

Randomized Embedded Adaptive Platform Clinical Trial in South Asian Kidney Biopsy-Proven Primary IgA Nephropathy: Multi-center, Multi-arm and Multi-stage

Global Burden of Diseases ranks chronic kidney disease (CKD) as the 12th leading cause of death, with an estimated 20% increase from 2010 to 2019. India is the most populous country in South Asia, with one-fourth of the global population. CKD prevalence has reached epidemic proportions in South Asia, with 1 in 7 adults affected by it. Glomerular diseases are the most common cause of CKD after diabetes and hypertension. IgAN is the most common primary glomerular disease in adults. In the Caucasian and East Asian populations, IgAN results in end-stage kidney disease (ESKD) in 15-20% of patients within 15-20 years after the first clinical presentation.
Our first prospective observational (GRACE-IgANI) cohort since 2015 showed that South Asians have severe and progressive IgAN, with 39% having a rapid fall in eGFR, 25% having non-remission of proteinuria, and 36% reaching an adverse kidney outcome at three years. Our group has shown that South Asian ethnicity is associated with a severe phenotype, rapid progression, and significant ethnic differences in biomarkers.
Over the last few years, newer anti-proteinuric agents and immunomodulatory drugs have either been approved by the FDA or are in the late phases of clinical trials for various proteinuric kidney diseases. The results of the STOP-IgAN and the recent TESTING trial have shown that the short-term beneficial effects of steroids on proteinuria and eGFR slope at six months wane over time, and there is a need for effective longer-term agents. The KDIGO guidelines development body on glomerular diseases has actively advocated enrolling patients prospectively in 'Clinical Trials'.
Platform trials are Multi-Arm and Multi-Stage (MAMS) randomised CTs comparing multiple parallel interventional groups against standardised common control groups with central coordination. It allows new interventions to be added, the control group to be updated throughout the trial, and the use of prespecified interim analysis plans for statistical efficiencies. Interventional groups can be introduced after the trial has started based on pre-specified criteria, and futile interventions may be stopped based on pre-specified interim analyses and trial-stopping rules.
This is a randomised controlled single-blind (outcome assessor) Platform trial, Multi-Arm and Multi-Stage. There is a single overarching protocol called a Master protocol. The master protocol, the common concurrent control arm for multiple interventions,the within-trial adaptations, the pre-specified interim analyses, and the pragmatic nature ensure greater acceptability and allow key trial characteristics to evolve. The overall strategy of the study relies strongly on pragmatic 'real world clinical situations' faced by practising nephrologists when treating adult patients with kidney biopsy-proven primary IgAN in South Asia. It will establish the 'GRACE Clinical Trial Network'.
The overarching trial hypothesis is that commonly available and approved generic drugs (low-dose oral prednisolone, gut-directed budesonide, mycophenolate mofetil, and hydroxychloroquine) in addition to Standard of Care (SoC), which is the maximal labelled or tolerated dose of renin-angiotensin system blockers (ACEi/ ARB) and a steady dose of sodium-glucose cotransporter 2 inhibitors (SGLT2i) can significantly improve the kidney outcomes at two years when compared to Standard of Care (SoC) alone in South Asian kidney biopsy-proven adult (≥18 years) primary IgAN who on follow-up remain at high risk of progression defined as UPCR ≥0.75g/g and baseline eGFR ≥20ml/min/1.73m2 despite good BP control. SoC is defined as a maximal labelled or tolerated dose of ACEi/ ARB and a steady dose of SGLT2i with a goal BP <140/90 mmHg for at least three months.

开始日期2024-11-01

申办/合作机构

Christian Medical College & Hospital

[+1]

NCT06408298 / Not yet recruiting早期临床1期IIT

A Randomized, Placebo Controlled Proof of Principle (Window of Opportunity) Study of Hydroxychloroquine (HCQ) in Prostate Cancer Patients Undergoing Radical Prostatectomy

This is randomized, double blind, placebo controlled proof of principle (window of opportunity) study of oral hydroxychloroquine in patients with resectable localized prostate cancer. To determine the effects of hydroxychloroquine (HCQ) on markers of autophagy, such as p62, LC3-II and NBR-1 in prostate cancer tissue of patients with resectable localized prostate cancer who undergo radical prostatectomy. To monitor/observe the safety and tolerability of daily oral hydroxychloroquine in the pre and perioperative period in patients who undergo radical prostatectomy. To evaluate the concentration of hydroxychloroquine in normal and prostate tumor tissue and to correlate prostate tissue concentrations with the plasma concentrations in these patients. To perform tumor genomic analysis (for common somatic mutations) and to correlate the molecular response to HCQ and presence/absence of such mutations.

开始日期2024-11-01

申办/合作机构

Dartmouth-Hitchcock Medical Center

100 项与硫酸羟氯喹相关的临床结果

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100 项与硫酸羟氯喹相关的转化医学

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100 项与硫酸羟氯喹相关的专利（医药）

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9,608

项与硫酸羟氯喹相关的文献（医药）

2025-03-01·Current Diabetes Reviews

Interferon Upregulation Associates with Insulin Resistance in Humans

Article

作者: Carneiro-Freire, Natalia ; Adeva-Andany, Maria M. ; Adeva-Contreras, Lucia ; Castro-Quintela, Elvira ; Ameneiros-Rodriguez, Eva ; Fernandez-Fernandez, Carlos

:In humans, insulin resistance is a physiological response to infections developed to supply sufficient energy to the activated immune system. This metabolic adaptation facilitates the immune response but usually persists after the recovery period of the infection and predisposes the hosts to type 2 diabetes and vascular injury. In patients with diabetes, superimposed insulin resistance worsens metabolic control and promotes diabetic ketoacidosis. Pathogenic mechanisms underlying insulin resistance during microbial invasions remain to be fully defined. However, interferons cause insulin resistance in healthy subjects and other population groups, and their production is increased during infections, suggesting that this group of molecules may contribute to reduced insulin sensitivity. In agreement with this notion, gene expression profiles [transcriptomes] from patients with insulin resistance show a robust overexpression of interferon-stimulated genes [interferon signature]. In addition, serum levels of interferon and surrogates for interferon activity are elevated in patients with insulin resistance. Circulating levels of interferon-γ-inducible protein-10, neopterin, and apolipoprotein L1 correlate with insulin resistance manifestations, such as hypertriglyceridemia, reduced HDL-c, visceral fat, and homeostasis model assessment-insulin resistance. Furthermore, interferon downregulation improves insulin resistance. Antimalarials such as hydroxychloroquine reduce interferon production and improve insulin resistance, reducing the risk for type 2 diabetes and cardiovascular disease. In addition, diverse clinical conditions that feature interferon upregulation are associated with insulin resistance, suggesting that interferon may be a common factor promoting this adaptive response. Among these conditions are systemic lupus erythematosus, sarcoidosis, and infections with severe acute respiratory syndrome-coronavirus-2, human immunodeficiency virus, hepatitis C virus, and Mycobacterium tuberculosis.

2025-01-01·Microvascular Research

Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography

Article

作者: Huang, Amy Michelle ; Qiu, Wangjian ; Li, Huangdong ; Zhang, Jingyu ; Wang, Li ; Xiang, Zheng ; Yin, Xi ; Liu, Zhiping ; Lv, Quan

AIMSTo explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA).METHODS40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry.RESULTSMacular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power.CONCLUSIONSLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.

2025-01-01·Colloids and Surfaces B: Biointerfaces

A new three-dimensional modeling of fluorescence excitation-emission measurements to explore the interaction of hydroxychloroquine and DNA, and to quantify their binding constant

Article

作者: DİNÇ, Erdal ; Üçer, Asiye ; ÜÇER, Asiye ; Dinç, Erdal

A new three-dimensional chemometric approach was introduced to explore the interaction of hydroxychloroquine (HCQ)-calf thymus deoxyribonucleic acid (DNA) and quantify binding constant using fluorescence excitation and emission measurements. The fluorescence excitation-emission spectra were recorded after gradual titration of HCQ with DNA. Then, the excitation and emission curves and relative concentrations of the drug and drug-DNA complex were quantitatively estimated using a three-dimensional model called Parallel Factor Analysis (PARAFAC) to a cubic fluorescence data array. The interaction of HCQ and DNA was predicted by applying newly modified Stern-Volmer equations to the relationship between the actual DNA concentration, and the HCQ concentration in the relative concentration profile of the PARAFAC model. In the PARAFAC application, the binding constants of the HCQ-DNA complex at 288, 298, and 310 K were found as 6.78 × 10³, 5.07 × 10³, and 3.74 × 10³ L mol^-1, respectively. From the temperature studies, the thermodynamic parameters (ΔS⁰= 3.528 J mol^-1 K^-1, ΔH⁰= -20.099 kJ mol^-1 and ΔG⁰=-21.11, -21.12, and -21.19 kJ mol^-1 at 288, 298, and 310 K, respectively) were calculated. The drug-DNA interaction is spontaneous due to negative ΔG⁰ values. The positive ΔS⁰ and negative ΔH⁰ values revealed the major role of the electrostatic force on the binding of HCQ to DNA. Assay results obtained from the proposed three-way modeling were compared to those provided by the traditional spectrofluorimetric method.

157

项与硫酸羟氯喹相关的新闻（医药）

2024-11-19

·EndPoints

Biogen, UCB detail response rates in Phase 3 lupus trial after surprising success

Biogen and UCB on Tuesday shared an expanded dataset for their Phase 3 lupus program, which they said two months ago succeeded in a pivotal trial. In the 321-patient study, dapirolizumab pegol achieved a 49.5% response rate after 48 weeks when combined with the standard of care, compared to a 34.6% response rate from the standard of care alone. The difference between the trial arms was statistically significant with a p-value of 0.0110, Biogen said. The drug also succeeded on several secondary endpoints, including the rates at which patients tapered off their corticosteroids. There were 156 patients whose steroid use was above 7.5 mg per day, and 72.4% who took dapirolizumab pegol reduced their steroid use by week 48 to at most 7.5 mg per day, compared to 52.9% in the standard of care arm. The nominal p-value was 0.0404. Additionally, there was a higher rate of serious side effects in the standard of care group — 9.9% of patients who took dapirolizumab pegol reported side effects, compared to 14.8% in the standard of care group. Coming off the surprising topline win in September, the results help establish the case for continuing the program after it failed a Phase 2 study in 2018. At the time, dapirolizumab pegol had only been slated for one Phase 3 study instead of the requisite two needed for FDA approval. But with the success this week, planning for another trial is already in progress. Most of the details remain a secret, Biogen immunology chief Diana Gallagher told Endpoints News , but the study is expected to start before the end of the year and will run for another 48 weeks. “It’ll have a lot of similarities to what we’ve done before,” she said. In the Phase 3 study, researchers evaluated patients’ responses using a composite lupus symptom score called British Isles Lupus Assessment Group-based Composite Lupus Assessment, or BICLA for short. A higher response rate is associated with improved symptoms across all affected organs from baseline measurements, Biogen said. The standard of care for lupus has remained largely static over many decades, with the two most commonly used treatments being steroids: hydroxychloroquine and prednisone, according to Duke University rheumatologist and the study’s principal investigator Megan Clowse. But the former is typically used in only the most severe cases to prevent death, while the latter comes with “terrible” side effects. “The real unmet need for patients living with lupus is, number one, being able to get away from chronic prednisone use,” Clowse said. There have been two approvals since 2011 in lupus — one for GSK’s Benlysta, and another for AstraZeneca’s Saphnelo. They have helped somewhat, but their impact is still limited, Clowse said. If dapirolizumab pegol gets past the finish line, it will continue to help patients control their inflammatory symptoms for longer periods of time and won’t “require six horse pills every day,” she said, referring to steroids. Much of the recent buzz around lupus R&D has dealt with CD19-targeting CAR-T. Dapirolizumab pegol takes a different approach, inhibiting CD40L signaling, according to Biogen. It’s hard to make a direct comparison to studies because the only published CAR-T data in lupus are in academic settings from a small number of extremely sick patients, according to Biogen’s Gallagher. But there will still be space for dapirolizumab pegol in the market, given that CD40L inhibition is not a currently available option for lupus patients, she added. “It’s pretty profound,” Gallagher said. “You really hit B cells, T cells. It really resets immunologically, but it’s well-tolerated based on our available data.”

临床结果临床3期临床2期免疫疗法细胞疗法

2024-11-16

·医药魔方Invest

前Biotech创始人和反疫苗人士加入特朗普团队，FDA将迎巨变？

特朗普赢得美国总统大选一周后，据外媒报道，14日，特朗普提名反疫苗活动家小罗伯特·F·肯尼迪（Robert F. Kennedy Jr.）领导卫生与公众服务部，此前他曾表示在上任后必将对FDA进行整改。无独有偶，两天前，特朗普还曾宣布埃隆·马斯克（Elon Musk）将与维维克·拉马斯瓦米（Vivek Ramaswamy）合作，领导一个新成立的政府效率部（DOGE）。据悉，该部门将提供来自政府外部的建议和指导，并与白宫和管理与预算办公室合作，推动大规模的结构改革，为政府创造前所未有的创业方式。相较于马斯克，同为商界大佬的拉马斯瓦米名气并不高，但提及其创办的生物技术企业Roivant，业内却并不陌生。而在新任职之前，拉马斯瓦米也曾参与本届总统竞选，并提出了一系列激进和颠覆性的政策主张。其中就包括他认为美国FDA“腐败”，发誓要“揭露并最终摧毁”FDA。这不禁令人好奇，此番加入“让美国再次伟大”的团队后，他们将给制药界带来如何影响？整改FDA的愿望清单今年70岁的肯尼迪是前参议员及司法部长罗伯特·F·肯尼迪的儿子，也是前总统约翰·F·肯尼迪的侄子。在提名前，小肯尼曾表达出要对FDA进行重大改组，消除FDA内部“腐败”的想法，也曾表示解雇FDA食品和营养部门全部工作人员后，将解雇美国国立卫生研究院的全部600名员工，用新员工换血。与此同时，据纽约时报报道，小肯尼迪上任后的愿望清单中，包括对生牛奶、羟氯喹、螯合剂、干细胞等领域的监督整改。以干细胞为例，近年来，干细胞治疗在医学领域引起了人们的关注。然而，在对革命性疗法抱有希望的同时，一些诊所却推销了未经FDA批准的药物。这让小肯尼迪对FDA在这方面的监督颇为不满。另外，小肯尼迪也或将对PDUFA法案进行一些改变。此前，应PDUFA法案规定，制药企业在向FDA提交申请时需要支付一定费用。这也被小肯尼迪视为FDA“腐败”的一大来源。获得提名后，小肯尼迪在社交平台上表示：“我们有了一个几十年一遇的机会，将科学、医学、工业和政府领域最杰出的人才聚集在一起，终结慢性病的流行。” 不过，对于这一提名，市场很快就给出了反馈。当天美股市场上，疫苗类股应声大跌。政府效率部再添新人，曾抨击FDA 与小肯尼迪想法一致，拉马斯瓦米也认为“这确实是百年一遇的机会。我们将对发现的政府浪费行为保持彻底透明。”13日，他在社交平台上发帖如此说道。然而，与拉马斯瓦米的摩拳擦掌相反，业界正陷入对削减FDA和其他卫生机构，甚至是行业倒退的担忧。 2021年，拉马斯瓦米辞去Roivant首席执行官一职，投身政界。这一年，正逢Roivant上市，到今年，该公司的股价今年上涨了近 40%，拉马斯瓦米所持10%股份的价值已升至约6亿美元。自9年前创立该公司以来，他已从Roivant以工资、奖金和资本收益的形式获得了超过2.6亿美元。据《福布斯》统计，大约一周前，这位38岁的商业大佬净资产已超过10亿美元，这使他成为美国20位最年轻的亿万富翁之一。拉马斯瓦米的商业天赋，大学时期便已显现。哈佛大学主修生物学时，拉马斯瓦米与他人共同创办了StudentBusinesses.com，这是一个供学生创始人向专业投资者推销的网站。据报道，一家私人慈善机构于2009年收购了该公司，收购金额不详。毕业后，他加入了对冲基金QVT，专门从事生物医药投资。职业生涯的前七年，他赚了700万美元，并在28岁时成为合伙人。单是投资研发出丙肝上市新药的Pharmasset，就让他在投资圈声名鹊起。也是在QVT工作期间，他发现很多大公司会因各种原因，放弃具有潜在治疗前景的在研新药分子。于是，拉马斯瓦米决定将想法落地，离开QVT并创办了Roivant。一年后，凭借从GSK低价买来的一款治疗阿尔兹海默症的药物Intepirdine（RVT-101），以及另一款从Arena制药公司“捡漏”得来的治疗失眠症药物，Roivant的第一个全资子公司Axovant以22亿美元的估值上市。当时，正是AD药物研发上屡遭挫折的年代。 Intepirdine的开发日后同样以失败告终，未能进入市场，而这样的结果似乎也影响了拉马斯瓦米对FDA的态度。此前他在竞选总统时，就曾提议采取大规模精简人员和关闭机构等重大行动，以及限制过度监管等。其中便包括FDA，他一直试图让其追随者相信FDA正在阻止人们获得药品，并认为FDA“行使的权力远远超出了FDA成立之初，法律设想的范围。” 去年12月份，拉马斯瓦米曾在社交平台发布视频，表示“腐败的FDA，对于开发十多年的药物，不敢尝试，但新冠疫苗却在不到1年就获批。” 他也多次重申对FDA“虚伪和有害”的批评。“多年来，业界资深人士一直教导我不要公开反对FDA。众所周知，如果你激怒FDA，他们会透过拒绝审查你的药物申请来惩罚你。” 靴子落地？外媒StatNews就称，拉马斯瓦米早期竞选总统的标签，就是对他不喜欢的政府机构进行批评，因此，FDA落入他的视野只是时间问题。那么政府效率部（DOGE）筹建后，FDA是否会走向精简和放松监管？ CBS新闻报道称，尽管特朗普表示，马斯克和拉马斯瓦米的工作“将在2026年7月4日前，也即《独立宣言》发表250周年前完成”，目标是“削减多余监管、削减浪费开支和重组联邦机构”，但目前关于该部门仅有一个轮廓，特朗普并无透露人员或资金将如何配置。与此同时，因为政府效率部并不是一个真正的政府部门，还需国会批准才能创建，且联邦财政支出需由国会批准，因此一切尚无定数。不过，马斯克和拉马斯瓦米皆信心满满。而同一天，FDA局长Robert Califf则表示出对特朗普政府上台后，FDA未来的担忧。眼下，小肯尼迪获得提名后，外媒报道称，小肯尼迪可能会面临一场艰难的提名确认战。如果提名获批，他将接管一个年度预算超过1.7万亿美元、拥有8万多名员工和13个业务部门的庞大机构，其中包括疾病控制与预防中心、美国国立卫生研究院和FDA。美国卫生部的大部分支出用于美国联邦医疗保险(Medicare)和医疗辅助计划(Medicaid)。可以预见，随着马斯克与拉马斯瓦米的加入，以及小肯尼迪成功上任，将或多或少给联邦机构，尤其是FDA带来不小的冲击。他们的改革是否会最终落地，FDA又将走向何方，这些问题的答案有望随着他们正式上任而逐渐明朗。参考资料 1. Financial Times：Vivek Ramaswamy’s FDA‘corruption’claims disavowed by Roivant 2. Forbes：How Vvek Ramaswamy became a billionaire? 3. Fiercepharma: After election, FDA's Califf lays out hopes for his Trump-appointed successor 4. CBS News：What to know about Trump's Department of Government Efficiency, led by Elon Musk and Vivek Ramaswamy 5.NewYork Times：Kennedy’s F.D.A. Wish List: Raw Milk, Stem Cells, Heavy Metals 推荐阅读特朗普再当选，将如何影响中国生物医药？ 12年医药风投人：FDA药审正在重回开放友好 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

疫苗高管变更加速审批

2024-11-15

·荣昌生物

免疫双擎，致胜未来！泰它西普治疗IgA肾病最新研究数据亮相2024 ASN

导读美国时间2024年10月24日~27日，一年一度的美国肾脏病学会年会暨肾脏周（2024 ASN Kidney Week）在圣地亚哥拉开帷幕，为肾脏病领域带来了一场酣畅淋漓的学术盛宴！免疫球蛋白A肾病（IgAN）是全球最常见的原发性肾小球疾病，IgAN临床表现及病理均多种、多样，其致病机制较复杂，其中B细胞的异常活化发挥了重要作用。新型药物泰它西普可同时靶向抑制增殖诱导配体（APRIL）和B淋巴细胞刺激因子（BLyS），并影响浆细胞自身抗体的分泌，减少免疫复合物在肾脏的沉积，为治疗IgAN提供新选择。本次大会上，有3篇壁报展示了泰它西普应用于IgAN的最新研究数据，为IgAN的临床治疗注入了新的生命力。 FR-PO893 IgAN新疗法的疗效与安全性比较：系统评价和网络荟萃分析研究标题 Comparative Efficacy and Safety of New Therapies for IgA Nephropathy: A Systematic Review and Network Meta-Analysis[1] 研究目的 IgAN可导致进行性肾功能障碍。该网络荟萃分析评估了针对IgAN机制的新疗法的疗效和安全性，并与标准治疗进行比较，旨在根据现有证据优化临床管理。研究方法研究评估了11项发表在过去10年的随机对照试验，共纳入861例 IgAN患者，采用贝叶斯网络荟萃分析比较了不同治疗方法与安慰剂的疗效，使用平均差异和 SUCRA 值评估最终结果，SUCRA值越高，药物的疗效越好。主要疗效指标为尿蛋白/肌酐比（UPCR）和估计肾小球滤过率（eGFR）随时间的变化。研究结果在降低UPCR方面，吗替麦考酚酯、阿塞西普和羟氯喹优于其他治疗方案，而布地奈德降低UPCR的疗效有限。在改善eGFR方面，泰它西普显示出较好的疗效，优于其它治疗选择，而氟替卡松在改善eGFR方面疗效欠佳（图1）。图1 主要疗效指标对比研究结论泰它西普和吗替麦考酚酯分别在改善eGFR和降低UPCR方面最有效，表明两者是IgAN患者的首选治疗方法。早在今年初，泰它西普一项II期、随机、双盲、安慰剂对照试验结果重磅发布！数据显示，泰它西普240mg组受试者24小时尿蛋白平均水平较基线下降了0.889g/24h（49%），P=0.013[2]。研究证实泰它西普可显著减少IgAN患者的蛋白尿，降低未来肾脏疾病进展的风险。 FR-PO865 泰它西普治疗IgAN的疗效和安全性：一项真实世界研究研究标题 Efficacy and Safety of Telitacicept in IgA Nephropathy: A Real-World Study[3] 研究目的 IgAN是全球最常见的原发性肾小球疾病，但其特异性治疗方法有限。泰它西普作为一种融合蛋白，由跨膜激活物、钙调节物、亲环蛋白配体相互作用物和 IgG 的结晶片段组成，可中和 B 淋巴细胞刺激剂和增殖诱导配体。四川大学华西医院肾内科的研究旨在评估泰它西普对成人 IgAN患者的疗效和安全性。研究方法研究纳入经活检证实的 24小时蛋白尿定量＞0.5g 且接受泰它西普（240mg qw）治疗（不联合糖皮质激素或免疫抑制剂）的IgAN患者，通过倾向评分匹配与仅接受支持治疗或免疫抑制治疗的患者进行 1:1 匹配，主要结果是3个月随访期间24小时蛋白尿相较基线的变化。研究结果泰它西普治疗组、支持治疗组、免疫抑制治疗组每组入组21例患者，平均eGFR为 80.1mL/min/1.73㎡，中位24小时尿蛋白定量1.48g/d。3 个月的随访期结束时： ·尿蛋白方面（图2），泰它西普治疗组中位24小时尿蛋白定量较基线减少 0.72g/d（54.6%），支持治疗组减少了0.18g/d（20%）（P<0.001），免疫抑制治疗组减少了1.12g/d（72.1%）（P=0.814）。图2 24小时蛋白尿较基线变化 ·肾功能方面（图3），泰它西普治疗组eGFR水平保持不变（1.9mL/min/1.73㎡[4.3%]），支持治疗组eGFR水平下降（-2.9mL/min/1.73㎡[-5.8%]），免疫抑制组eGFR水平下降（-6.1mL/min/1.73㎡[-8.4%]）。图3 eGFR较基线变化 ·安全性方面，泰它西普治疗组未见严重不良事件发生。注射部位反应多见于泰它西普治疗组（8/21，[38.1%]），免疫抑制组呼吸道感染较多（7/21，[33.3%]）。研究结论泰它西普可以减少 IgAN患者的蛋白尿，并显示出良好的安全性。 SA-PO882 宫颈涂片检查后发生IgA沉积为主的感染相关性新月体性肾小球肾炎研究标题 IgA-Dominant Postinfectious Crescentic Glomerulonephritis after a Cervical Smear[4] 研究目的 IgA沉积为主的感染相关性肾小球肾炎（IRGN）通常表现为弥漫性毛细血管内和/或系膜增生，可伴有少量新月体。复旦大学附属中山医院肾内科报告了一例罕见的IgA为主型的IRGN伴弥漫性坏死性细胞新月体的患者病例，经糖皮质激素联合环磷酰胺、泰它西普治疗后获益。病例描述一例29岁妇女在接受宫颈涂片检查后出现快速进行性水肿和无尿，伴发热和持续阴道脓流。实验室检查显示血肌酐723μmol/L，白蛋白17.4g/L，CRP172mg/L，低补体血症，以及显著蛋白尿和血尿。抗肾小球基底膜（GBM）抗体、抗中性粒细胞胞浆抗体（ANCA）阴性。阴道分泌物培养检出粪肠球菌。肾活检（图4）免疫荧光显示IgA和C3沿毛细血管袢壁呈星空状沉积。光镜下肾小球90%可见坏死性细胞新月体，毛细血管内增生，鲍曼囊壁断裂。电镜下可见上皮下和内皮下电子致密沉积。因此诊断为IgA沉积为主型IRGN。图4 肾活检组织病理学结果在感染得到控制后，给予甲泼尼龙脉冲治疗和环磷酰胺静脉注射。3天后患者尿量开始增加，2周后脱离透析。经过9个月周期性静脉滴注环磷酰胺、口服激素逐渐减量的治疗，患者肾功能部分恢复，仍有中等水平蛋白尿（图5），因而行重复肾活检评估疾病活动度。免疫荧光见系膜区和毛细血管壁少量IgA沉积。光镜下显示53%肾小球硬化，纤维性新月体28%，间质纤维化/肾小管萎缩（IFTA）占皮质区域50%。予以停用糖皮质激素和环磷酰胺，并换用泰它西普。在4个月的随访中，患者蛋白尿完全缓解，eGFR得到改善（图5）。图5 治疗及随访情况病例讨论 IgA沉积为主型IRGN可表现为弥漫坏死性病变和新月体肾炎，类似ANCA相关肾炎。除控制感染外，及时的免疫抑制对肾功能的恢复至关重要，泰它西普可能是治疗IgA沉积为主型IRGN的潜在药物。结语上述3项研究摘要结果显示，泰它西普可降低IgAN患者的蛋白尿，同时维持肾功能的稳定，且在安全性方面表现良好。令人惊喜的是，今年多篇泰它西普相关研究亮相国际舞台，第 61 届欧洲肾脏协会年会（ERA 2024）上，泰它西普有4篇研究亮相；2024亚太肾脏病学大会暨韩国肾脏病学会年会（APCN&KSN）上，泰它西普有7篇研究亮相；全球华人肾脏病学术大会暨香港肾科学会周年学术会议2024（ICCN 2024），泰它西普有1篇研究亮相。临床数据均得到国际认可，表明泰它西普在IgAN领域中具有潜在的治疗价值，彰显了全球影响力。但未来仍需更大规模的临床研究来进一步验证这些发现。目前，泰它西普正在进行的用于IgAN治疗的 III 临床试验已完成入组，期待未来该项研究能带来更为亮眼的数据，进一步丰富泰它西普治疗IgAN的证据链，为患者带来新选择。参考文献： 1.Larissa A. Lucena, et al. Comparative Efficacy and Safety of New Therapies for IgA Nephropathy: A Systematic Review and Network Meta-Analysis. 2024 ASN; FR-PO893. 2.Jicheng Lv, et al. Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria[J]. Kidney Int Rep. 2022;8(3):499-506. 3.Lingqiu Dong, et al. Efficacy and Safety of Telitacicept in IgA Nephropathy: A Real-World Study. 2024 ASN;FR-PO865. 4.Shi Jin, et.al. IgA-Dominant Postinfectious Crescentic Glomerulonephritis after a Cervical Smear. 2024 ASN;SA-PO882. 来源 | 医脉通肾内频道荣昌生物科创板上市 | 港交所上市挺进医保 | License out 维迪西妥单抗 | 泰它西普 RC28 | RC108 | RC118

临床结果临床2期

100 项与硫酸羟氯喹相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02114	硫酸羟氯喹	P01BA02	DB01611

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
盘状红斑狼疮	美国	Novitium Pharma LLC初创企业	2022-01-14
疟疾	美国	Novitium Pharma LLC初创企业	2022-01-14
皮肤红斑狼疮	日本	Sanofi KK	2015-07-03
急性疟疾	美国	Concordia Pharmaceuticals, Inc.	1955-04-18
类风湿关节炎	美国	Concordia Pharmaceuticals, Inc.	1955-04-18
系统性红斑狼疮	美国	Concordia Pharmaceuticals, Inc.	1955-04-18

未上市

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
新型冠状病毒感染	临床3期	美国	Novartis Pharmaceuticals Corp.	2020-05-01
胰腺继发性恶性肿瘤	临床2期	爱尔兰	Novartis AG	2023-05-31
胰腺腺癌	临床2期	美国	West Virginia University Hospitals, Inc.	2020-02-04
晚期胰腺腺癌	临床1期	美国	Novartis Pharmaceuticals Corp.	2019-01-18
转移性胰腺腺癌	临床1期	美国	Novartis Pharmaceuticals Corp.	2019-01-18
不能切除性胰腺癌	临床1期	美国	Novartis Pharmaceuticals Corp.	2019-01-18
盘状红斑狼疮	临床前	中国	Viatris, Inc.	2022-09-07
新型冠状病毒感染	临床前	美国	Novartis Pharmaceuticals Corp.	2020-05-01
原发性干燥综合征	临床前	法国	Sanofi	2008-03-01
风湿性疾病	临床前	-	Sandoz International GmbH	1993-07-01

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临床结果

适应症

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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


NCT04318444 (CTgov)	临床2/3期	新型冠状病毒感染	10	Hydroxychloroquine (Hydroxychloroquine Group)	醖鬱簾壓衊網觸獵淵獵(鏇齋願壓鹽憲觸構艱簾) = 選鹽夢遞夢鑰壓獵窪網繭夢網簾鬱夢鏇膚壓餘 (齋獵積簾築繭築鑰範衊, 鑰鬱衊膚衊鹹襯齋窪齋 ~ 齋繭襯鏇醖鏇鑰鬱鏇網) 更多	-	2024-09-25
				Placebo (Placebo Group)	醖鬱簾壓衊網觸獵淵獵(鏇齋願壓鹽憲觸構艱簾) = 顧鬱觸蓋鹽廠築網蓋餘繭夢網簾鬱夢鏇膚壓餘 (齋獵積簾築繭築鑰範衊, 選襯鏇衊夢選選窪觸獵 ~ 築衊艱獵顧築簾壓觸築) 更多
NCT03598595 (ESMO2024) 人工标引	临床1/2期	骨肉瘤	31	Gemcitabine + Docetaxel + Hydroxychloroquine	(淵顧廠願醖窪觸網鏇膚) = 製鬱蓋廠膚齋壓範構鹽膚窪膚鑰醖淵齋築蓋顧 (鹹顧餘鏇醖餘鑰窪艱選 ) 更多	积极	2024-09-14
NCT04527549 (CTgov)	临床2期	皮肤黑色素瘤 \| 不可切除的黑色素瘤 \| 局部晚期黑色素瘤	5	Dabrafenib mesylate+Hydroxychloroquine+Trametinib dimethyl sulfoxide (Arm A (Dabrafenib, Trametinib, Hydroxychloroquine))	範齋餘齋憲蓋網鏇蓋選(窪鏇餘構餘齋顧鑰願構) = 簾襯構襯積壓艱膚鬱襯醖願齋夢鬱廠淵夢選鏇 (製構壓願襯網夢窪淵積, 糧餘壓醖鏇廠鬱範繭獵 ~ 醖製網蓋獵淵範淵衊顧) 更多	-	2024-08-22
				Placebo Administration+Dabrafenib mesylate+Trametinib dimethyl sulfoxide (Arm B (Dabrafenib, Trametinib, Placebo))	範齋餘齋憲蓋網鏇蓋選(窪鏇餘構餘齋顧鑰願構) = 壓選鹽觸鬱簾餘醖齋鏇醖願齋夢鬱廠淵夢選鏇 (製構壓願襯網夢窪淵積, 膚衊窪餘觸淵繭餘艱鬱 ~ 顧蓋選衊顧鑰積壓壓壓) 更多
GR2 (GR2, EULAR2024)	N/A	系统性红斑狼疮 HCQ blood levels	174	HCQ blood levels ≤500 ng/ml	壓淵窪齋衊鏇構遞製遞(築醖繭範醖願蓋衊蓋糧) = 淵簾構顧餘獵蓋製範鬱醖蓋餘獵糧壓遞鑰淵構 (觸鏇製夢網積醖壓窪繭 ) 更多	积极	2024-06-05
				HCQ blood levels >500 ng/ml	壓淵窪齋衊鏇構遞製遞(築醖繭範醖願蓋衊蓋糧) = 簾鹽鹹鏇醖蓋餘鏇繭壓醖蓋餘獵糧壓遞鑰淵構 (觸鏇製夢網積醖壓窪繭 ) 更多
EULAR2024	N/A	视网膜疾患	-	HYDROXYCHLOROQUINE (HCQ) (HCQR patients)	(膚膚遞鏇醖鑰構鏇鑰製) = 憲顧齋鏇構夢願淵廠鏇範遞觸餘鹽鏇壓範遞積 (夢鹹繭觸壓鹹齋醖網鏇, 48 ~ 62)	-	2024-06-05
				HYDROXYCHLOROQUINE (HCQ) (Controls)	(膚膚遞鏇醖鑰構鏇鑰製) = 願襯淵壓壓壓蓋糧積夢範遞觸餘鹽鏇壓範遞積 (夢鹹繭觸壓鹹齋醖網鏇, 48 ~ 62)
EULAR2024	N/A	毒性	-	hydroxychloroquine (Patients referred in 2018-2019)	構窪廠觸膚願選鏇網餘(鏇窪構糧鏇網壓簾範遞) = 鑰壓鹽餘範醖淵築蓋鏇顧構齋鹽製憲顧構艱範 (製廠製齋顧鹹構窪簾蓋 )	-	2024-06-05
ATS2024	N/A	-	-	Hydroxychloroquine 400mg/daily	餘觸範製選願顧糧艱積(範窪壓鑰淵網遞襯觸膚) = The patient reported feeling palpitations, lightheadedness, fatigue with nausea and vomiting for 24 hours. The patient reported multiple episodes of hypoglycemia for the past year without a history of diabetes or exogenous insulin use. Blood glucose on admission was found to be 53 mg/dl. During the admission the patient's blood sugar continued to decline requiring additional D10w. The patient returned to the hospital with symptoms of hypoglycemia. 獵鑰獵簾築壓醖簾艱繭 (觸願憲製選蓋觸糧製憲 ) 更多	-	2024-05-19
NCT04341727 (WU352, CTgov)	临床3期	新型冠状病毒感染 \| 严重急性呼吸综合征	30	Hydroxychloroquine Sulfate (Hydroxychloroquine Alone)	憲鹽獵餘範襯鹹廠鑰製(膚獵製簾製鏇壓壓鏇繭) = 憲窪繭糧選憲鑰獵襯鏇願鑰願餘夢網廠築簾廠 (簾遞餘鏇遞齋壓鏇衊衊, 願製築醖獵製窪鑰鑰鹹 ~ 鹽蓋簾齋獵夢鹹衊襯夢) 更多	-	2024-04-25
				Hydroxychloroquine Sulfate+Azithromycin (Hydroxychloroquine Plus Azithromycin)	憲鹽獵餘範襯鹹廠鑰製(膚獵製簾製鏇壓壓鏇繭) = 觸齋艱獵積構醖獵餘壓願鑰願餘夢網廠築簾廠 (簾遞餘鏇遞齋壓鏇衊衊, 醖簾憲齋鏇淵簾製網築 ~ 餘願膚遞選築襯網壓餘) 更多
NCT03428945 (TN-22, CTgov)	临床2期	1型糖尿病 \| 葡萄糖耐受不良	273	Hydroxychloroquine (Hydroxychloroquine)	選餘衊壓醖膚膚襯淵簾(願築壓顧衊壓艱糧餘鹽) = 遞範簾淵廠構襯鏇網鑰遞網簾積壓選膚鹹鬱鑰 (選鹽鑰鹽遞窪窪積齋鹹, 積憲築選顧觸網憲衊築 ~ 鏇鏇淵獵窪餘襯鬱築範) 更多	-	2024-04-09
				Placebo (Placebo)	選餘衊壓醖膚膚襯淵簾(願築壓顧衊壓艱糧餘鹽) = 窪膚簾構範範襯鬱夢膚遞網簾積壓選膚鹹鬱鑰 (選鹽鑰鹽遞窪窪積齋鹹, 簾繭憲淵壓鹽夢淵艱憲 ~ 遞衊鏇壓餘願網鏇淵範) 更多
NCT04321278 \| NCT04322123 (COALITION II, Pubmed) 人工标引	临床3期	新型冠状病毒感染	1,114	Hydroxychloroquine	廠淵艱衊鹹構壓鹽窪淵(蓋鹹製簾網積廠襯簾範) = 蓋餘餘鬱齋襯衊襯積願鹹製遞觸觸積衊鏇觸艱 (製願遞糧積窪窪範壓鬱 ) 更多	积极	2024-03-01
				Hydroxychloroquine+ Azithromycin	廠淵艱衊鹹構壓鹽窪淵(蓋鹹製簾網積廠襯簾範) = 網簾壓蓋齋齋鑰鹹廠鬱鹹製遞觸觸積衊鏇觸艱 (製願遞糧積窪窪範壓鬱 ) 更多