A Phase 1, Open-Label Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults

In this study, researchers will learn more about a study drug called BIIB080. BIIB080 is currently a drug under investigation for treatment of Alzheimer's disease. The main question researchers are trying to answer in this study is how radiolabeled BIIB080 distributes in the brain and spinal cord. To help answer this question, researchers will use positron emission tomography (PET) scanner that can detect radiolabeled BIIB080 after a single injection of a small dose of radiolabeled BIIB080 ([89Zr]Zr-DFO-BIIB080) and a dose of BIIB080 together via an intrathecal (IT) injection in healthy volunteers. Researchers will also learn about the safety of injecting radiolabeled BIIB080 and BIIB080 together.

开始日期2025-03-20

申办/合作机构

Biogen, Inc.

NCT05399888

/ Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of BIIB080 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease Dementia

In this study, researchers will learn more about a study drug called BIIB080. The study will focus on participants with mild cognitive impairment or mild dementia due to AD.
The main question researchers are trying to answer is if BIIB080 can slow the worsening of AD more than placebo. It will focus on what dose of BIIB080 slows worsening of AD the most.
To help answer this question, researchers will use the Clinical Dementia Rating-Sum of Boxes, also known as the CDR-SB.
* Clinicians use the CDR-SB to measure several categories of dementia symptoms.
* The results for each category are added together for a total score. Lower scores are better.
Researchers will also learn more about the safety of BIIB080.
The study will be split into 2 parts. The 1st part is the Placebo-Controlled Period. The 2nd part is the Long-Term Extension (LTE) Period. The 2nd part of the study will help researchers learn about the long-term safety of BIIB080, and how it affects the participant's daily life, thinking, and memory abilities in the longer term.
A description of how the study will be done is given below.
* After screening, participants will first receive either a low dose or high dose of BIIB080, or a placebo, as an injection into the fluid around the spinal cord (cerebrospinal fluid). A placebo looks like the study drug but contains no real medicine.
* Participants will receive BIIB080 or placebo once every 12 weeks or 24 weeks.
* After 76 weeks of treatment in the Placebo-Controlled Period, eligible participants will move onto the Extension Treatment period, which will last 96 weeks.
* In the extension period, participants who received placebo will be switched to high dose BIIB080 every 12 or 24 weeks.
* Participants may be in the study for up to 201 weeks, or about 4 years. This includes the screening and follow-up periods.
* Participants can continue to take certain medications for AD. Participants must be on the same dose of medication for at least 8 weeks before the screening period.
* After the screening period, most participants will visit the clinic every 6 weeks.

开始日期2022-08-24

申办/合作机构

Biogen, Inc.

NL-OMON55789

/ RecruitingN/A

A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients with Mild Alzheimer*s Disease - ISIS 814907-CS1

开始日期2018-01-04

申办/合作机构

Ionis Pharmaceuticals, Inc.

100 项与 ISIS-814907 相关的临床结果

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100 项与 ISIS-814907 相关的转化医学

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100 项与 ISIS-814907 相关的专利（医药）

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项与 ISIS-814907 相关的文献（医药）

2023-12-01·JAMA neurology

Exploratory Tau Biomarker Results From a Multiple Ascending-Dose Study of BIIB080 in Alzheimer Disease

Article

作者: Martarello, Laurent ; Kordasiewicz, Holly ; Wu, Shuang ; Mignon, Laurence ; Ziogas, Nick ; Beaver, John ; Hutchison, R. Matthew ; Budd Haeberlein, Samantha ; Li, Yumeng ; Lin, Lin ; DuBois, Jonathan ; Lane, Roger ; Junge, Candice ; Edwards, Amanda L. ; Collins, Jessica A. ; Shulman, Melanie ; Graham, Danielle

Importance:

Accumulation of hyperphosphorylated, tangled microtubule-associated protein tau (MAPT) is a pathological hallmark of Alzheimer disease (AD) associated with disease progression and cognitive decline.

Objective:

To evaluate the effect of tau synthesis reduction on tau biomarkers in patients with mild AD.

Design, Setting, and Participants:

This randomized clinical trial was a double-blind, placebo-controlled 36-week multiple-ascending dose (MAD) phase 1b trial (October 2017 to September 2020), followed by a 64- or 71-week open-label long-term extension (LTE) (October 2019 to May 2022). After being assessed for eligibility at 12 sites in Canada and Europe, participants with mild AD and confirmed amyloid pathology were randomized 3:1 (BIIB080:placebo) in 4 dose cohorts.

Intervention:

Intrathecal administration of BIIB080, a MAPT-targeting antisense oligonucleotide, or placebo. Active dose arms included 10 mg every 4 weeks, 30 mg every 4 weeks, 60 mg every 4 weeks, and 115 mg every 12 weeks during the MAD period and 60 mg every 12 weeks or 115 mg every 12 weeks during the LTE.

Main Outcome and Measures:

The original primary end point was safety. Additionally, BIIB080, total tau (t-tau), and phosphorylated tau 181 (p-tau181) cerebrospinal fluid (CSF) concentrations were evaluated. Tau positron emission tomography (PET) was collected in a substudy, and standard uptake value ratios (SUVRs) were calculated in a priori-defined composite regions of interest.

Results:

Of 102 participants assessed for eligibility, 46 participants with mild AD were enrolled; 23 (50%) were female, and mean (SD) age was 65.8 (5.70) years. BIIB080 was generally well tolerated and was associated with a dose-dependent reduction in CSF t-tau and p-tau181 in the MAD period (56% reduction; 95% CI, 50% to 62%; and 51% reduction; 95% CI, 38% to 63%, of CSF t-tau in the 2 higher-dose cohorts) that continued and/or was maintained through quarterly dosing in the LTE. Tau PET demonstrated reduced accumulation vs placebo at week 25 (n = 13). At week 100, tau PET showed a reduction from baseline across all regions assessed (n = 12), with the largest reductions from baseline observed in the temporal composite (−0.71 SUVR; 95% CI, −1.40 to −0.02). A moderate correlation was observed between model-predicted cumulative CSF drug exposure and tau PET change.

Conclusions and Relevance:

In this randomized clinical trial, BIIB080 reduced tau biomarkers, including CSF t-tau, CSF p-tau181, and tau PET, which is associated with cognitive decline, in participants with mild AD. Effects of BIIB080 on biomarkers and clinical outcomes are being further evaluated in a phase 2 trial.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03186989

2023-05-04·Expert opinion on drug discovery

The development of peptide- and oligonucleotide-based drugs to prevent the formation of abnormal tau in tauopathies

Review

作者: Sardone, Rodolfo ; Dibello, Vittorio ; Castellana, Fabio ; Panza, Francesco ; Lozupone, Madia ; Bellomo, Antonello ; Bortone, Ilaria ; Altamura, Mario ; Solfrizzi, Vincenzo ; Daniele, Antonio ; Zupo, Roberta ; Lampignano, Luisa ; Stallone, Roberta

INTRODUCTION:

Tauopathies represent clinicopathological entities with increased and abnormal glial and/or neuronal inclusions of tau, a microtubule-binding protein. Antisense oligonucleotides (ASOs) are a promising therapeutic approach for treating tauopathies as they can target tau mRNA to reduce total human tau expression or tau exon 10 expression and 4 R tau. Additionally, targeting the tau specifically with peptides may be a unique pharmacological approach, between small molecules and proteins.

AREAS COVERED:

The present review investigates the chemical basis of designing ASOs and peptides currently known to treat tauopathies. Among ASOs targeting tau expression, BIIB080 was the first to enter clinical trial development for treating mild Alzheimer's disease (AD). Furthermore, the therapeutic potential of peptide 021 (P021, Ac-DGGLAG-NH2) in tauopathies is discussed based on preclinical studies.

EXPERT OPINION:

ASOs are a promising therapeutic approach for tauopathies, particularly because ASOs may suppress the expression of harmful genes and are directly delivered to the brain, showing little systemic side effects. However, whether a generalized brain tau decrease will produce positive clinical effects remains unclear. A Phase II trial of BIIB080 is ongoing in mild AD. Neurotrophic and neurogenic peptide mimetic compounds have also shown potential as treatment options for AD and other tauopathies.

项与 ISIS-814907 相关的新闻（医药）

2025-02-13

·研发客

渤健放弃4条神经类药物管线

根据渤健（Biogen）最新发布的2024年财报，该公司宣布终止了4款神经类药物的开发，包括针对糖尿病周围神经性疼痛的BIIB143（cemdomespib）、针对早期阿尔茨海默病的BIIB113、针对早期帕金森的BIIB094和针对多系统萎缩症的BIIB101。其中，BIIB143是渤健在去年7月斥资73亿美元收购Reata Pharmaceuticals公司而获得的重要资产。根据ClinicalTrials.gov的数据，BIIB143针对糖尿病周围神经性疼痛的2期临床研究原计划于2026年8月结束。另外3个项目均处于1期临床阶段。BIIB113是通过阻止tau蛋白聚集来治疗早期阿尔茨海默病的口服小分子药物。虽然该项目被终止，但渤健的另一款针对tau蛋白的治疗早期阿尔茨海默症的反义寡核苷酸BIIB080的2期研究仍继续进行。 BIIB094和BIIB101是渤健同Ionis合作开发的反义寡核苷酸药物。虽然靶向LRRK2的BIIB094被砍掉了，但渤健仍对通过该机制治疗帕金森感兴趣，另一款基于类似机制的BIIB122目前处在2期临床研究阶段。渤健的研发负责人Priya Singhal博士在财报分析的电话会上分享了削减项目背后的考虑。他提到，为了重新平衡风险，并投资在未来预期可增长的关键领域，渤健将开发重点集中在了一小部分临床阶段项目上。这些项目具有较高的可信度，并且渤健已做好充分准备，可以按计划定期推进关键性临床试验和潜在的上市工作。总第2334期访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

临床2期财报寡核苷酸并购临床1期

2025-02-12

·FierceBiotech

Biogen axes asset from $7.3B buyout, along with Alzheimer’s and Parkinson’s prospects

Biogen ousted cemdomespib alongside three phase 1 assets. \n Biogen is continuing to thin its pipeline, dropping a phase 2 program acquired in the $7.3 billion Reata Pharmaceuticals buyout and kicking early-stage Alzheimer’s and Parkinson’s prospects into touch.The big biotech used its fourth quarter results to reveal (PDF) it is ending the development of four molecules, one phase 2 prospect in diabetic peripheral neuropathic pain and three phase 1 neurodegenerative disease programs. Priya Singhal, M.D., head of development of Biogen, discussed the thinking behind the cuts on the company’s earnings call Wednesday.“We have previously discussed our efforts to augment our pipeline with the objective of rebalancing the risk profile and investing to win in key areas of expected future growth. As a result, we have focused our development efforts on a smaller set of clinical-stage programs that we believe are high conviction and well positioned to deliver a regular cadence of pivotal readouts and potential launches,” Singhal said.BIIB143, also known as cemdomespib, was the most advanced asset to get the chop. Biogen acquired the Hsp90 modulator in 2023 through its buyout of Reata, a deal that centered on the FDA-approved Skyclarys. Reata took the molecule into a phase 2 diabetic peripheral neuropathic pain trial weeks after accepting Biogen’s buyout bid. The trial is set to wrap up in August 2026, according to ClinicalTrials.gov, but Biogen has already seen enough to call time on the program.The big biotech ousted cemdomespib alongside three phase 1 assets. An oral small molecule designed to treat early Alzheimer’s by stopping tau aggregation led the early-phase discontinuations. Biogen finished a phase 1 trial of the drug candidate, BIIB113, in 2023. Work on another tau-focused treatment of early Alzheimer’s, the phase 2 antisense oligonucleotide BIIB080, is continuing.In early Parkinson’s, Biogen stopped the development of the Ionis-partnered BIIB094. The antisense oligonucleotide targets LRRK2, reflecting evidence that gain-of-function mutations in the gene are the most common genetic cause of Parkinson’s. Biogen retains an interest in treating Parkinson’s by targeting LRRK2, with BIIB122, an inhibitor of the protein, remaining in the biotech’s phase 2 pipeline.Finally, Biogen brought an end to the development of BIIB101 in multiple system atrophy. The antisense oligonucleotide, another product of Biogen’s work with Ionis, targets alpha-synuclein. Insoluble forms of alpha-synuclein accumulate in the brains of multiple system atrophy patients, leading Biogen to identify the protein as a driver of neurodegeneration.

并购临床2期寡核苷酸临床1期上市后研究

2025-01-24

·药时代

股价大涨16%，口服小分子阿尔茨海默病药物临床结果积极

2025年1月23日，Vigil Neuroscience宣布其核心管线VG-3927，在用于阿尔茨海默病（AD）的一期临床试验中结果积极。受此消息影响，Vigil股价当日收盘大涨15.76%。图片来源：雪球 VG-3927是一款口服小分子TREM2激动剂，旨在激活TREM2跨膜受体蛋白，强化小胶质细胞的修复能力，从而清除淀粉样蛋白斑块沉积达到AD治疗的目的。可简单理解为，小胶质细胞就是大脑中的“清洁工”，作为大脑中的常驻先天免疫细胞，它能够形成免疫屏障以及发挥类似巨噬细胞的吞噬功能，清扫大脑中的“垃圾”。而TREM2专门表达在大脑中的小胶质细胞表面，就像劳务所下达劳务派遣，让AD患者脑内处于休息状态的“清洁工”，重新开始工作。根据Vigil早期研究表明，sTREM2（可溶性TREM2）在AD患者脑脊液中升高，与AD进程密切相关。且TREM2还在淀粉样蛋白病理学和淀粉样蛋白诱导的tau病理学中都具有保护作用。因此，具有较好溶解度、口服生物利用度和CNS摄取特征的VG-3927，备受业内关注。此次一期临床试验中，VG-3927在患者脑脊液中实现了高达约50%的游离TREM2（sTREM2）显著剂量依赖性降低，且显示出高脑外显率、可耐受的安全性。这意味着，VG-3927作为全球首款用于AD治疗、目前临床进展最快的口服小分子TREM2激动剂，再次证明了这条通路用于治疗AD的可行性，对后来者有着借鉴与鼓舞作用。目前，针对TREM2受体的药物研发多是集中在AD领域。其中，由Alector与艾伯维合作开发的TREM2单抗AL002刚于去年11月份宣布临床失败，Alector无奈终止了该药物的长期拓展研究，并裁员17%。表格来源：格宁生物众所周知，鉴于AD病因尚不明确，相关药物的研发失败率极高。据不完全统计，AD药物的研发失败率高达99.6%，进入21世纪以来，已有超过320项临床试验宣告失败，如罗氏、强生、辉瑞、默沙东等各大MNC均折戟于此，而癌症药物的研究失败率则为 81%，因此AD领域也被业内称之为“研发黑洞”。近年来，随着Aduhelm、Leqembi以及Donanemab的相继获批，AD药物研发并入快车道。基于Aβ、Tau蛋白、神经炎症、突触可塑性等各科假说的在研药物如雨后春笋般冒出，百花齐放，好不热闹。一个刚起步且庞大的市场，是吸引玩家争相涌入的必要条件。根据国际AD协会网站显示，2030年，AD患者数量预计将攀升至7800万，医疗费用花销将达2.8万亿美元。然而，纸面的数字无法兑现现实的期许。首款Aβ单抗Aduhelm的获批，虽备受争议，但却被业内推测为史上最畅销的药物之一，结果仅在2023年取得480万美元的销售额后就被放弃，或许我们可以将其归因于临床不认可所致，但同样具备高评价的Leqembi，商业化依旧不尽人意。如今，Donanemab在上市之初也被投行给出了高达30多亿美元巅峰销售额的预测，不过鉴于上市不久，能否达到预期还要打个问号。上市才是开始，商业化才是药物的最后一公里。目前，Biogen对Leqembi的拓展方向主要就是新剂型和新给药方法，包括静脉给药维持疗法、自动注射器皮下给药维持疗法以及自动注射器皮下给药初始治疗。其中一个重要原因就是剂型所困。像基础设施制约，Leqembi需要每月两次给药，接受治疗的AD患者需要在专科中心输液。卷“剂型”成为必然。目前在研AD药物中，上市的口服剂型仅有寥寥几款。2014年，首款获FDA批准的是美金刚/多奈哌齐复方制剂，第二款时隔十年，是2024年批准的Zunveyl。值得一提的是，2025年1月8日，康哲宣布引进Zunveyl在亚洲（除日本）、澳洲、新西兰的独家权益，总协议金额为4000万美元。不难看出，口服AD药物的吸引力。当今值得注意的口服药物有，Aβ靶点：Alzheon的ALZ-801；神经炎症靶点：AB Science的马赛替尼、BioVie的NE3107等。国内方面，其实很早就有甘露特纳（九期一），作为首款靶向肠-脑轴的AD药物，在我国较为出名。小结 VG-3927的早期临床试验成功，其主要意义是对AD新通路的再次验证，特别是走在TREM2领域前沿的AL002失利之后。其次，就是激化了口服AD药物的市场竞争。同时，在考虑解决依从性的问题时，还应考虑对现有疗法的改进，如Donanemab在用药过程中，需经PET检测确定出现Tau蛋白水平符合要求的减少后停药，那么何时复查？PET检测价格也是影响用药依从性的影响因素。最后，则是对AD新药安全性的重申，像脑水肿、脑出血等副作用仍是已上市药物的痛点。VG-3927在早期临床中显示，所有不良事件（AE）均为轻度或中度严重，所有AE均在无干预的情况下消退，且到目前为止还没有严重的伤亡报告。此外，VG-3927面临的挑战也是巨大的。除了其他口服剂型外，还未进入临床二期的VG-3927还将面临Biogen的AD疫苗BIIB080可能带来的冲击，目前该ASO疗法处在临床二期。参考资料： 1.Vigil Neuroscience官网 2.TREM2受体在多种致死疾病中起关键作用（格宁生物） 3.阿尔茨海默病治疗又有新进展！这两个新疗法你知道吗？（医学界神经病学频道） 4.摸不准的AD市场（佰傲谷BioValley） 5.其他公开资料封面图来源：pixabay 传奇/ 强生卖了近10亿美元！百万元疗法的商业路，何时能走通？ 2025-01-23 中国生物技术崛起撼动美国制药业领导地位？ 2025-01-22 药明生物想当的，是中国创新药出海的最佳拍档 2025-01-21 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击，查看更多精彩!

临床2期临床1期临床结果

100 项与 ISIS-814907 相关的药物交易

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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
认知功能障碍	临床2期	美国	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	日本	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	澳大利亚	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	比利时	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	加拿大	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	捷克	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	丹麦	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	芬兰	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	法国	Biogen, Inc.	2022-08-24
认知功能障碍	临床2期	德国	Biogen, Inc.	2022-08-24

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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


NCT03186989 (Literature) 人工标引	临床1期	阿尔茨海默症 Tau protein	46	BIIB080	觸餘網鹽網蓋願範觸膚(鏇衊構窪醖壓網窪繭壓) = 蓋鏇糧壓膚範願範顧憲齋廠築膚壓壓廠衊膚餘 (簾選範醖獵簾蓋壓鏇壓, 50 ~ 62) 更多	积极	2023-10-30
NCT03186989 (Literature) 人工标引	临床1期	阿尔茨海默症 Tau protein	46	placebo	-	积极	2023-10-30
NCT03186989 (NEWS) 人工标引	临床1期	阿尔茨海默症	46	BIIB080	製壓網製壓選憲鑰壓蓋(簾積製網齋鏇壓廠醖夢) = 繭範獵衊糧艱鬱淵醖製製積齋顧鹽選鏇膚遞獵 (簾網顧餘艱糧願網遞觸 )	积极	2023-10-26
NCT03186989 (PRNewswire) 人工标引	临床1期	阿尔茨海默症	46	BIIB080 (low dose group treated every four-weeks)	鹽壓廠鑰襯選醖簾顧繭(醖構鏇鹹網鏇積築壓鑰) = All adverse events were mild to moderate in severity with no serious adverse events occurring in any patients that received BIIB080. There were no deaths, dose-limiting adverse events or dosing discontinuations. 夢襯窪繭襯壓餘獵衊簾 (衊築淵艱壓選淵觸淵壓 ) 达到	积极	2023-08-16
NCT03186989 (PRNewswire) 人工标引	临床1期	阿尔茨海默症	46	BIIB080 (medium dose group treated every four-weeks)		积极	2023-08-16
NCT03186989 (Ionis-MAPT Rx CS1, AAN2018)	临床1/2期	阿尔茨海默症	-	IONIS-MAPT Rx	繭遞餘醖鏇遞築鹹襯範(襯窪衊製齋襯鹹鹽夢餘) = 衊壓醖餘壓蓋蓋構積構觸網積襯築餘構鹽願鏇 (構選壓鑰獵鑰鏇簾餘膚 )	积极	2018-04-10
Ionis-MAPTRx-CS1 (ANA2017)	N/A	阿尔茨海默症	-	Ionis-MAPTRx	繭構夢觸夢襯選憲鬱壓(齋網簾衊淵衊膚鏇簾積) = 鹽觸範襯鏇鹽顧構窪窪鹽膚憲願鏇製選壓夢鹹 (夢鹹憲顧網繭積夢構製 )	-	2017-10-15
Ionis-MAPTRx-CS1 (AAIC2017)	N/A	阿尔茨海默症	-	Ionis-MAPTRx	網積積繭築衊廠網鬱觸(構積鏇遞鹽網鹽積積齋) = 壓鏇膚鹹鬱壓夢簾鏇壓憲構蓋遞選鏇醖獵衊網 (窪衊壓淵窪顧築網積鏇 )	-	2017-07-01