A PHASE 3, MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF CSL112 IN SUBJECTS WITH ACUTE CORONARY SYNDROME

开始日期2020-01-12

申办/合作机构

CSL Behring LLC

ACTRN12618000805279 / Completed临床1期

A phase 1, randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetics, safety, and tolerability of CSL112 in healthy Japanese and Caucasian subjects

开始日期2018-05-16

申办/合作机构

CSL Ltd.

NCT02742103 / Completed临床2期

A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Moderate Renal Impairment and Acute Myocardial Infarction

This study is a phase 2, multicenter, double-blind, randomized, placebo controlled, parallel-group study to investigate the renal safety and tolerability of multiple dose intravenous (IV) administration of CSL112 compared with placebo in subjects with moderate renal impairment (RI) and acute myocardial infarction (AMI).

开始日期2016-08-01

申办/合作机构

CSL Behring LLC

100 项与 CSL-112 相关的临床结果

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100 项与 CSL-112 相关的转化医学

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100 项与 CSL-112 相关的专利（医药）

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322

项与 CSL-112 相关的文献（医药）

2023-11-01·The Journal of biological chemistry

Retardation of Aβ42 fibril formation by apolipoprotein A-I and recombinant HDL particles

Article

作者: Linse, Sara ; Sparr, Emma ; Frankel, Rebecca

The double nucleation mechanism of amyloid β (Aβ) peptide aggregation is retained from buffer to cerebrospinal fluid (CSF) but with reduced rate of all microscopic processes. Here, we used a bottom-up approach to identify retarding factors in CSF. We investigated the Aβ42 fibril formation as a function of time in the absence and presence of apolipoprotein A-I (ApoA-I), recombinant high-density lipoprotein (rHDL) particles, or lipid vesicles. A retardation was observed in the presence of ApoA-I or rHDL particles, most pronounced with ApoA-I, but not with lipid vesicles. Global kinetic analysis implies that rHDL interferes with secondary nucleation. The effect of ApoA-I could best be described as an interference with secondary and to a smaller extent primary nucleation. Using surface plasmon resonance and microfluidics diffusional sizing analyses, we find that both rHDL and ApoA-I interact with Aβ42 fibrils but not Aβ42 monomer, thus the effect on kinetics seems to involve interference with the catalytic surface for secondary nucleation. The Aβ42 fibrils were imaged using cryogenic-electron microscopy and found to be longer when formed in the presence of ApoA-I or rHDL, compared to formation in buffer. A retarding effect, as observed in CSF, could be replicated using a simpler system, from key components present in CSF but purified from a CSF-free host. However, the effect of CSF is stronger implying the presence of additional retarding factors.

2023-10-01·Protein expression and purification

Isolation of recombinant apolipoprotein E4 N-terminal domain by foam fractionation.

Article

作者: Ryan, Robert O ; Kiss, Robert S ; Hafiane, Anouar ; Lethcoe, Kyle ; Fox, Colin A

Apolipoprotein (apo) E functions in lipoprotein metabolism as a low density lipoprotein receptor ligand. ApoE is comprised of two structural domains, a 22 kDa N-terminal (NT) domain that adopts a helix bundle conformation and a 10 kDa C-terminal domain with strong lipid binding affinity. The NT domain is capable of transforming aqueous phospholipid dispersions into discoidal reconstituted high density lipoprotein (rHDL) particles. Given the utility of apoE-NT as a structural component of rHDL, expression studies were conducted. A plasmid construct encoding a pelB leader sequence fused to the N-terminus of human apoE4 (residues 1-183) was transformed into Escherichia coli. Upon expression, the fusion protein is directed to the periplasmic space where leader peptidase cleaves the pelB sequence, generating mature apoE4-NT. In shaker flask expression cultures, apoE4-NT escapes the bacteria and accumulates in the medium. In a bioreactor setting, however, apoE4-NT was found to combine with gas and liquid components in the culture medium to generate large quantities of foam. When this foam was collected in an external vessel and collapsed into a liquid foamate, analysis revealed that apoE4-NT was the sole major protein present. The product protein was further isolated by heparin affinity chromatography (60-80 mg/liter bacterial culture), shown to be active in rHDL formulation, and documented to serve as an acceptor of effluxed cellular cholesterol. Thus, foam fractionation provides a streamlined process to produce recombinant apoE4-NT for biotechnology applications.

2023-09-20·Molecules (Basel, Switzerland)

Comparison of Policosanols via Incorporation into Reconstituted High-Density Lipoproteins: Cuban Policosanol (Raydel^®) Exerts the Highest Antioxidant, Anti-Glycation, and Anti-Inflammatory Activity.

Article

作者: Nam, Hyo-Seon ; Baek, Seung-Hee ; Cho, Kyung-Hyun ; Kim, Ji-Eun ; Kang, Dae-Jin

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel^®), China (Shaanxi Pioneer), and the United States (Lesstanol^®) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 μg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML.

项与 CSL-112 相关的新闻（医药）

2024-02-19

·药时代

6年1.8万名受试者参与的10亿美元豪赌：失败了也值得尊敬

正文共：3223字 6图预计阅读时间：9分钟澳洲药企CSL在2018年立下一场豪赌，希望通过一场涉及来自49个国家850多个地点的18,000多名患者的Ⅲ期临床试验来证明CSL112的市场价值。这场临床试验规模之浩大，甚至超过司美格鲁肽的Select试验（17,604名受试者入组）。CSL估算这场临床试验可能会耗资8亿澳元（约5.23亿美元），但具体开支众说纷纭，Evaluate Pharma预测该药物至2020年的临床研究花费就会达到6.21亿美元，临床研究总投入有可能会达到26.9亿美元。加拿大皇家银行（RBC）的分析师则指出，CSL已经花费了“近10亿美元用于开发和测试它”。无论采信哪一方的估计，就规模与投入成本而言，CSL的这项Ⅲ期试验都是有载入药物研发史册的机会的。好在作为全球最大的血液制品供应商之一，CSL有充分的现金为CSL112买单。这项代号为AEGIS-II的试验一旦成功，那么一个在全球拥有2亿名患者的百亿美元市场将拥入CSL之手。可惜一切仅限于如果——2024年2月11日，CSL公布CSL112Ⅲ期试验AEGIS-II的主要结果：未达到降低急性心肌梗死（AMI）后患者主要不良心血管事件（MACE）风险的主要终点。理论上是这样的……CSL112是一种由血浆衍生的载脂蛋白A-I，该蛋白是高密度脂蛋白（HDL）的主要功能成分。HDL的主要生理功能是负责将血液中的磷脂和胆固醇转运回肝脏储存，因此往往被称作“好胆固醇”，与另一种会导致一系列心血管疾病的“坏胆固醇”低密度脂蛋白（LDL）相对应。在一些早期的临床观察中，心血管疾病的发生风险似乎与”坏胆固醇“正相关，与”好胆固醇“负相关。从朴素的观点出发，如果可以增强胆固醇的排出能力，也应该可以加速血管中斑块的清除……对吧？还真不是这样，在CSL112之前，也有许多的药企希望通过提升HDL水平来治疗患者，但是无一例外都失败了，所以CSL将之前的失败案例定义为没有实际改善患者的胆固醇排出能力，HDL送进身体里不干活，那就没意义了。而CSL112的Ⅱb期临床试验已经充分论证了患者在接受CSL112治疗后，可以提升胆固醇排出能力，是有在确实提升HDL功能，而不是单纯的提高患者体内表达HDL的水平。图片来源：Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction | Circulation (ahajournals.org)2016年的公司新闻稿中指出患者的胆固醇排出速率立刻提升了四倍，从指标上来看还是很不错的……图片来源：CSL官网实践咋不一样了呢？但Ⅱb期研究居然没有得出任何能够证明CSL112能够降低患者心血管不良事件发生风险的结论！多个次要终点的HR＞1和P＞0.05印证这款药物的实际作用可以说与安慰剂无异（甚至更糟？）。甚至在两个剂量组中，有多达9名患者发生全因死亡，而安慰剂组只有1例！图片来源：Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction | Circulation (ahajournals.org)投资者不能理解，研究团队难以相信，这与当时普遍认知的基础医学理论完全不符！失败的试验仍在继续因此CSL认为这是因为Ⅱb期试验主要衡量的是药物安全性，整个试验围绕衡量CSL112的安全性设计，没有足够证据来评估疗效，所以还是要通过Ⅲ期临床试验来证明这款药物的疗效。图片来源：Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction | Circulation (ahajournals.org)Ⅱb期的临床试验数据“不足为信”也有一定的合理性，但是数据如此悲观必然已经让CSL意识到了某些可能。毕竟有1400名患者入组，这样的次要终点数据必然不是废纸。所以18000余名患者入组，也许是想要豪赌一个可能性——不是药物没有疗效，而是CSL112的疗效过于薄弱，导致需要更多证据证明其确有疗效。在药物商业化历史上，也确实存在不少疗效薄弱，但是通过临床试验的大入组人数或者严密的临床设计把P值压在0.01以下，拿到了明确的”具有疗效“证据的案例。这也在相当程度上这也能体现出CSL对基础科学理论的笃信，以及对CSL112的自信。在CSL所认可，也是当时普遍共识的学科理论中，急性冠脉综合征（包括心肌梗死、不稳定心绞痛等）患者疾病发作后的前90天最为危险，一年内约60%的复发性主要不良心血管事件发生在这段时间之中（这也是AEGIS-II的试验设计中会将90天作为界限的原因）。如果能在心脏病发作后迅速从斑块中去除胆固醇，就有可能在这段危险期中稳定动脉危险病变，否则这些病变可能会爆发并导致另一次心血管事件。图片来源：CSL官网但生命科学这个”黑箱“再次印证了它的不可捉摸。如今，这个18000人的试验没有证明CSL112具有疗效，反倒是可以证明：“提升胆固醇排出率≠降低患者心血管事件复发风险”。CSL已放弃为CSL112提交上市申请。这不是一个让人意外的结果。认知的改变就在CSL得出Ⅱb期结果的第二年，也就是2017年，美国医学会心脏病学杂志（JAMA Cardiol）刊登了一篇来自中国的研究报告（Association of CETP Gene Variants With Risk for Vascular and Nonvascular Diseases Among Chinese Adults）。这篇研究报告描述了一种特殊的基因变异，拥有这类变异的人群 HDL-C 水平显著升高，但 LDL-C 水平基本不变。在分析其 10 年随访结果后发现，这种变异并没有降低心脑血管疾病（例如冠心病和脑卒中）的发病风险。这项研究回应了一个问题，即在不减少LDL-C水平的情况下，单纯增加HDL-C水平，并不能对心血管疾病起到保护作用。这也是一个重大的认知进步，以往认为高密度脂蛋白水平上升，低密度脂蛋白水平下降，即可认为药物起效，但实际上在相当长的一段时间之内，我们并不了解究竟是哪一种脂蛋白才是影响心血管风险的关键。2022年7月，JAMA Cardiol刊登的Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations则论证了患者HDL-C水平与全因病死率和心血管病死率之间呈U型曲线关系，即HDL-C水平越高，不良后果的风险程度越高。这或许能论证，单纯提升患者的高密度脂蛋白水平，可能对患者无益，甚至有害。为何要尊重这种失败对于CSL而言，投资规模如此之大的Ⅲ期临床试验既是面对巨大市场诱惑的一场豪赌，必须承认如果仅以药物研发的角度去审视这个结果会令人感到非常遗憾。但人类对于基础科学认知的进步正是建立在无数的试错之上，CSL的结论对于心血管疾病的研究依然具有长远的意义。CSL 执行副总裁兼研发主管 Bill Mezzanotte 博士是这么为AEGIS-II挽尊的：“AEGIS-II是我们公司历史上最雄心勃勃的研究，我们为我们交付的研究质量以及我们为此开发的增强能力感到自豪。我们计划将这些能力以及我们的血浆蛋白平台应用于未来未满足的心血管和代谢疾病以及我们其他战略治疗领域的医疗需求。“这是一段得体的悼词。参考资料Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction | Circulation (ahajournals.org)CSL tumbles as key heart attack drug fails trial, why the market is so disappointed (marketindex.com.au)心血管病学 | “好胆固醇”并非越高越好！我国HDL-C水平与脑卒中关系呈U型|HDL-C|风险|脑卒中|研究|心血管|-健康界颠覆认知！升高 HDL-C 水平能降低心血管疾病风险吗？- 丁香园封面图来源：pixabay争夺药王宝座之外，火辣滚烫的GLP-1还有哪些宏伟目标和看点？诺和诺德、辉瑞、礼来、阿斯利康、安进谁将笑到最后？为什么说这一疗法获批上市，是一个历史性时刻？司美格鲁肽片剂技术解构及其隐性知识的启示点击这里，欣赏更多精彩内容！

临床结果临床2期临床失败临床3期

2024-02-15

·BioSpace

ABIONYX Pharma Acknowledges the Clinical Results of the Phase 3 AEGIS-II Study Evaluating the Efficacy and Safety of CSL Behring’s Human-plasma-derived apoA-I, CSL112

TOULOUSE, France & LAKELAND, Mich.--(BUSINESS WIRE)-- Access here the full press release ABIONYX Pharma, (FR0012616852 – ABNX – PEA PME eligible), a new generation biotech company dedicated to the discovery and development of innovative therapies based on the world’s only natural recombinant apoA-I, today acknowledges that the Phase 3 AEGIS-II study evaluating the efficacy and safety of CSL Behring’s human-plasma-derived apoA-I, CSL112, compared to placebo in reducing the risk of major adverse cardiovascular events (MACE) in patients following an acute myocardial infarction (AMI), did not meet its primary efficacy endpoint of MACE reduction at 90 days. About CER-001 CER-001 is a novel engineered recombinant human apoA-I that was designed to mimic the structural and functional biological properties of natural, nascent HDL, also known as pre-β HDL, and has been shown to perform all steps of the Reverse Lipid Transport pathway (RLT), the only natural pathway responsible for lipid elimination. Administered CER-001 particles increase transient apoA-I and the number of HDL particles and promote the elimination of trapped cholesterol and lipids in tissues in the absence of LCAT enzyme for example, but also the elimination of bacterial lipid endotoxin (LPS) in the case of sepsis. HDL particles are then recognized by the liver, leading to the elimination of these transported lipids via a process called Reverse Lipid Transport (RLT). About ABIONYX Pharma ABIONYX Pharma is a next-generation biotech company focused on developing innovative medicines in diseases where there is no effective or existing treatment, even the rarest ones. The company expedites the development of novel therapeutics through an extensive expertise in lipid science and a differentiated apoA-I -based technology platform. ABIONYX Pharma is committed to radically improving treatment outcomes in sepsis and critical care. View source version on businesswire.com: Contacts NewCap Investor relations Nicolas Fossiez Louis-Victor Delouvrier abionyx@newcap.eu +33 (0)1 44 71 98 53 NewCap Media relations Arthur Rouillé abionyx@newcap.eu +33 (0)1 44 71 00 15 Source: ABIONYX Pharma View this news release online at:

临床3期临床结果

2024-02-12

·FierceBiotech

CSL's 'most ambitious' phase 3 trial ends in failure for heart attack drug

CSL Behring’s share price dropped around 5% when the Australian stock exchange opened Monday. CSL Behring’s largest-ever trial has ended in failure, as the Australian pharma revealed that its cholesterol efflux enhancer was unable to reduce the risk of heart attacks. The company had been testing CSL112, also known as apolipoprotein A-I, in a study of about 17,400 heart attack patients spread across 49 countries. The first participant was dosed in the AEGIS-II study in 2018. But the trial failed to hit its primary endpoint of showing a reduction in the risk of major adverse cardiovascular events after 90 days when compared to placebo, CSL disclosed in a Feb. 11 release. “As a result, there are no plans for a near-term regulatory filing,” the company concluded. CSL didn’t share many other details, although it did point out that there were no major safety or tolerability concerns with the drug. Instead, the company said it would share primary results at the American College of Cardiology Scientific Sessions in April. “Substantial work remains to fully analyze and understand the complete data and then to determine any development path ahead for this asset,” CSL’s head of R&D Bill Mezzanotte, M.D., said in the release. “AEGIS-II is the most ambitious study in our company's history and we are proud of the quality of the study we delivered and the enhanced capabilities we developed to do so,” Mezzanotte added. “We plan to apply these capabilities as well as our plasma protein platform to future unmet medical need in cardiovascular and metabolic conditions as well as those in our other strategic therapeutic areas.” CSL112 was developed using a new formulation of apoA-I, the main component of high-density lipoproteins, which was extracted from human plasma. By enhancing the body’s ability to remove cholesterol from plaque in the arteries, the hope was that CSL112 would reduce cardiovascular events among high-risk patients in what CSL had described as the “critical 90 days after a heart attack.” When the trial was designed back in 2017, CSL executives suggested that CSL112 had “the potential to change the current treatment paradigm for heart attack survivors and improve global health outcomes for the millions of people at risk for early recurrent cardiovascular events.” The company’s share price dropped around 5% when the Australian stock exchange opened Monday, with CSL’s shares ending the day’s trading at 290.24 Australian dollars compared to a Friday closing price of AU$305.

临床3期AHA会议

100 项与 CSL-112 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
急性冠状动脉综合征	临床3期	美国	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	日本	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	阿根廷	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	澳大利亚	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	奥地利	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	比利时	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	巴西	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	保加利亚	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	加拿大	CSL Behring LLC	2018-03-21
急性冠状动脉综合征	临床3期	智利	CSL Behring LLC	2018-03-21

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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


NCT03473223 (AEGIS-II, Pubmed)	临床3期	急性心肌梗塞 low cholesterol efflux - \| apolipoprotein A1	-	CSL112	鏇餘製窪淵衊鹹衊繭糧(齋憲鹹衊齋齋獵壓窪糧) = a higher number of hypersensitivity events was reported in the CSL112 group 構選憲觸齋廠製構襯夢 (築選簾襯觸網顧餘齋範 )	不佳	2024-04-06
				Placebo
NCT03473223 (AEGIS-II, Biospace) 人工标引	临床3期	急性冠状动脉综合征	18,200	CSL112	獵窪糧鏇醖鬱獵觸廠繭(繭選獵積鏇鹽鬱選齋積) = did not meet its primary efficacy endpoint of MACE reduction. 衊糧衊鑰糧遞鹹糧艱觸 (遞艱鏇壓鏇構鏇觸觸願 ) 未达到	不佳	2024-02-15
				Placebo
NCT02108262 (AEGIS-I, CTgov)	临床2期	急性心肌梗塞	1,267	Placebo	餘願選鏇構範遞餘製鏇(範糧窪廠壓築繭憲觸製) = 願衊積齋範膚鬱廠鏇獵獵壓餘選醖蓋築廠積選 (製構廠鹹壓鹽鏇衊窪網, 積願遞獵襯餘夢遞衊廠 ~ 遞積窪膚廠製糧構構鑰) 更多	-	2021-03-15
NCT02742103 (CSL112_2001 \| CSL112-2001, CTgov)	临床2期	急性心肌梗塞	83	CSL_112 (CSL_112)	餘膚積觸夢夢齋選壓鹹(壓繭鏇繭顧淵獵製繭構) = 觸壓鏇醖顧齋糧獵積壓襯願膚獵簾壓製製獵衊 (膚願餘襯鑰鏇範獵築廠, 構壓觸顧壓鑰獵積鹽鹽 ~ 繭觸壓艱襯衊網構範蓋) 更多	-	2020-06-11
				Placebo (Placebo)	餘膚積觸夢夢齋選壓鹹(壓繭鏇繭顧淵獵製繭構) = 壓襯艱選製餘鹹觸鬱壓襯願膚獵簾壓製製獵衊 (膚願餘襯鑰鏇範獵築廠, 壓餘構夢齋憲築齋糧窪 ~ 鑰襯夢壓襯簾鹹獵廠鬱) 更多
NCT02427035 (Pubmed) 人工标引	临床1期	肾功能不全	32	CSL112	鹹壓夢廠餘範鹽鹹網積(簾顧遞願淵築鹽鏇衊鬱) = 願網蓋衊淵範夢窪蓋製鏇鬱構艱壓鏇齋廠窪範 (淵衊醖襯淵窪網獵願夢 ) 更多	积极	2019-07-01
NCT02742103 (CSL112-2001, Pubmed) 人工标引	临床2期	肾功能不全 \| 急性心肌梗塞	83	CSL112	構繭鬱糧鑰齋壓鹽襯蓋(顧顧鹽壓構餘鏇膚衊顧) = 衊鑰製鏇觸窪繭簾廠獵淵艱鹹遞夢鹽蓋淵遞鏇 (艱憲選壓願願選遞築鑰 ) 更多	积极	2019-02-01
				Placebo	構繭鬱糧鑰齋壓鹽襯蓋(顧顧鹽壓構餘鏇膚衊顧) = 製膚願襯壓鏇憲網淵廠淵艱鹹遞夢鹽蓋淵遞鏇 (艱憲選壓願願選遞築鑰 ) 更多
EASD2018	N/A	Apolipoprotein A-I	-	ApoA-I	淵淵網襯餘鏇蓋選範繭(鹽鏇艱製鏇築蓋顧範鹹) = 鹽鏇淵選襯繭繭餘襯觸醖遞觸憲獵選淵築衊蓋 (積簾夢衊蓋餘獵簾淵齋 ) 更多	积极	2018-10-05
NCT02108262 (AEGIS-I, Pubmed \| Circulation) 人工标引	临床2期	急性心肌梗塞	1,258	CSL112	簾憲積願鑰憲糧鹽繭製(鏇憲遞獵齋構鹹衊網夢) = The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. 窪壓鹽醖觸獵襯鬱範鏇 (範餘窪鑰觸簾範積鏇繭 ) 更多	积极	2016-12-13
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ARVO2015	N/A	视黄醇结合蛋白缺乏症	-	Apolipoprotein A-I	餘齋鹹顧鹽膚醖壓獵衊(積膚夢衊繭齋構糧艱遞) = 觸窪艱網廠鑰糧襯窪憲鹽夢遞憲膚製簾簾壓觸 (衊鬱顧範鏇築積鑰糧壓 )	-	2015-06-01