Tau PET Longitudinal Substudy Associated With: A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-randomized, Placebo-treated Non-carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease

This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).

开始日期2019-06-10

申办/合作机构

Hoffmann-La Roche, Inc.

[+2]

NCT03491150

/ Terminated临床3期

A Multicenter, Open-Label, Long-Term Extension Of Phase III Studies (BN29552/BN29553) Of Crenezumab In Patients With Alzheimer's Disease

In the BN40031 OLE study, a dose of crenezumab of 60 mg/kg intravenous (IV) every 4 weeks (Q4W) will be offered to all participants who complete Study BN29552 or BN29553 and who meet eligibility criteria in order to evaluate safety in participants on long-term crenezumab treatment and to investigate the effect of crenezumab on the underlying disease process and disease course as an exploratory efficacy objective.

开始日期2018-04-11

申办/合作机构

Hoffmann-La Roche, Inc.

NCT03114657

/ Terminated临床3期

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer's Disease

This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD. Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab or placebo every 4 weeks (Q4W) for 100 weeks. The primary efficacy assessment will be performed at 105 weeks. The participants who do not enter open-label extension will enter for a long term follow-up period for up to 52 weeks after the last crenezumab dose (Week 153).

开始日期2017-03-29

申办/合作机构

Hoffmann-La Roche, Inc.

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100 项与克雷内治单抗相关的专利（医药）

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项与克雷内治单抗相关的文献（医药）

2026-02-01·LANCET NEUROLOGY

Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1 mutation at risk for autosomal-dominant Alzheimer's disease in Colombia (API ADAD Colombia Trial): a phase 2, randomised, double-blind, placebo-controlled trial

Article

作者: Sink, Kaycee M ; Xu, Yi Ran ; Bittner, Tobias ; Ríos-Romenets, Silvia ; Langbaum, Jessica B ; Doody, Rachelle S ; Dolton, Michael ; Espinosa, Alejandro ; Giraldo-Chica, Margarita ; Ospina, Paula ; Schneider, Lon S ; Thomas, Ronald G ; Nguyen, Jonas ; Villegas, Gustavo ; Muñoz, Claudia ; Collazos, Mario Muñoz ; Cai, Yuqi ; Reiman, Eric M ; Quiroz, Yakeel T ; Cardona, Eugenia ; Selkoe, Dennis J ; Lopez, Hugo ; Luna, Ernesto ; Tirado, Victoria ; Clayton, David ; Alvarez, Sergio ; Ashton, Nicholas J ; Tariot, Pierre N ; Denkinger, Marisa N ; Schneider, Andres ; Sánchez, Gregorio ; Castaño, Marisol Londoño ; Chen, Kewei ; Poon, Victor ; Acosta-Baena, Natalia ; Jakimovich, Laura J ; Bocanegra, Yamile ; Hu, Nan ; Ostaszewski, Beth ; Su, Yi ; Alexander, Robert C ; Henao, Eliana ; Lopera, Francisco S ; Aguillón, David

BACKGROUND:

To have maximal benefit, Alzheimer's disease-modifying treatments might need to be started before the onset of clinical symptoms. Mutations of the PSEN1 gene are inherited as fully penetrant, autosomal-dominant traits, which almost always result in the clinical onset of Alzheimer's disease before the age of 65 years. We aimed to evaluate the efficacy, including possible delayed emergence of cognitive impairment, and safety of crenezumab, an anti-amyloid monoclonal antibody, in cognitively unimpaired carriers of the PSEN1^Glu280Ala mutation at high imminent risk of developing symptoms due to Alzheimer's disease.

METHODS:

This 5-8-year common-close, double-blind, placebo-controlled, single-centre trial screened kindred members aged 30-60 years from the main health-care site in Medellín, Colombia. Participants who were cognitively unimpaired and carried the PSEN1^Glu280Ala autosomal-dominant mutation were randomly assigned 1:1 to receive placebo or subcutaneous crenezumab (investigators and participants were masked to treatment allocation), with an initial 300 mg dose every 2 weeks that increased to 720 mg every 2 weeks, and a later optional increase to 60 mg/kg intravenously every 4 weeks. Randomisation was stratified by age, education, APOE ɛ4 carrier status, and baseline Clinical Dementia Rating. Mutation non-carriers received placebo and were included in a 1:2 ratio of non-carriers to carriers to maintain genotype masking and include a genetic kindred control. Dual primary outcomes were the annualised rates of change in the Alzheimer's Prevention Initiative (API) preclinical autosomal-dominant Alzheimer's disease (ADAD) composite test total score and Free and Cued Selective Reminding Test-Cueing Index (FCSRT-CI) assessed in randomised participants who received at least one dose of the study drug, according to treatment assignment. Primary endpoints were assessed with a random coefficient regression model with a missing-at-random assumption adjusting for randomisation factors. Safety endpoints for mutation carriers were assessed in randomised participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT01998841) and is completed.

FINDINGS:

619 Colombian API registrants were prescreened, 315 were assessed for eligibility, and 252 were enrolled (crenezumab-carrier, n=85; placebo-carrier, n=84; placebo-non-carrier, n=83; 160 [63%] women and 92 [37%] men) between Dec 20, 2013, and Feb 27, 2017. 237 (94%) completed the trial, with final data collection on March 22, 2022. The annualised rate of change in the API ADAD composite was -1·10 (SE 0·29) in the crenezumab group and -1·43 (0·29) in the placebo group (between-group difference 0·33 [95% CI -0·48 to 1·13]; p=0·43). The annualised rate of change in FCSRT-CI was -0·03 (0·00) in the crenezumab group and -0·04 (0·00) in the placebo group (between-group difference 0·01 [0·00 to 0·02]; p=0·16). All participants had at least one adverse event; serious adverse events occurred in 23 (27%) of 84 in the crenezumab group and 21 (25%) of 84 in the placebo group. No fatalities occurred.

INTERPRETATION:

Crenezumab therapy administered for 5-8 years did not result in significant benefits on our primary clinical outcomes in cognitively unimpaired participants predisposed to developing ADAD dementia; secondary and exploratory outcomes also showed no significant effect on removal of amyloid plaques or other clinical or biomarker outcomes. Together with the results of other anti-amyloid β trials, robust fibrillar amyloid removal appears necessary for clinical efficacy in people with elevated brain amyloid. This study will further inform the biomarker, cognitive, and clinical trajectory of preclinical ADAD, the risk of clinical progression in amyloid-positive and amyloid-negative mutation carriers, and the size and design of future secondary and primary prevention trials.

FUNDING:

US National Institute on Aging (NIA), Banner Alzheimer's Institute, Genentech, F Hoffmann-La Roche.

2025-12-01·Alzheimers & Dementia

Characterizing Tau Accumulation and Amyloid‐Tau Interactions in the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Colombia Trial and Their Implications for Advancing Drug Development

Article

作者: Tatton, Nadine ; Reiman, Eric M. ; Klein, Gregory ; Pedretti, Nicolo Foppa ; Su, Yi ; Karten, Yashmin ; Tariot, Pierre N. ; Alexander, Robert C. ; Zhang, Yi ; Insel, Philip S.

Abstract:

Background:

Alzheimer’s disease (AD), particularly its autosomal dominant form (ADAD), presents unique challenges for drug development. Clinical trials involving cognitively healthy individuals with ADAD can provide a useful model for sporadic Alzheimer's disease. They can aid in studying the early stages of the disease, which is challenging in sporadic cases due to heterogeneity. The CPAD consortium integrates clinical trial and observational data to develop tools to accelerate drug development. A key goal is to create a comprehensive drug‐disease‐trial model for ADAD, using data from multiple sources to address critical questions on tau and amyloid pathologies, biomarker‐cognition relationships, and disease progression.

Methods:

The Alzheimer’s Prevention Initiative ADAD Colombia Trial1 is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired Presenilin 1 (PSEN1) E280A kindred members. Initial research questions guiding this study include: (1) evaluating regional tau accumulation patterns in ADAD compared to sporadic AD to determine whether the same brain regions show the fastest tau accumulation; and (2) estimating the association between changes in regional tau and amyloid PET to assess whether local amyloid‐tau relationships within regions are stronger than across‐brain correlations. We use a linear mixed effect model to evaluate longitudinal outcomes with a model specification including fixed effects for mutation status, time, interaction terms, and random effects structured to account for individual heterogeneity. Model comparison techniques are used to select the most parsimonious random effects structure, focused on regional tau accumulation patterns and amyloid‐tau relationship dynamics across brain regions.

Results:

Linear mixed effect models revealed distinct tau accumulation patterns in carriers compared to non‐carriers. Regional tau protein accumulation differed across brain regions, with specific variations in baseline amyloid‐related dynamics and demographic effects. The analysis distinguished cognitive progression characteristics between ADAD and sporadic AD, highlighting longitudinal neurodegenerative mechanisms.

Conclusion:

We characterize distinct tau accumulation patterns and amyloid‐tau interactions, particularly in ADAD mutation carriers, offering valuable insights into early disease progression. We tested our model assumptions and methods, further strengthening the framework for advancing therapeutic research and understanding the neurodegenerative mechanisms underlying both ADAD and sporadic AD.

2025-12-01·Alzheimers & Dementia

Estimated age of amyloid plaque onset and impact of APOE4 in longitudinally assessed presenilin 1 E280A autosomal dominant Alzheimer’s disease mutation carriers

Article

作者: Duque, Sindy ; Su, Yi ; Protas, Hillary D. ; Guerrero, Alejandro ; Espinosa, Alejandro ; Alexander, Robert C. ; Leon‐Varela, Yudy M ; Quiroz, Yakeel T. ; Lopera, Francisco ; Aponte, Claudia ; Langbaum, Jessica B. ; Sohankar, Javad ; Alvarez, Sergio ; Baena, Ana Y ; Chen, Yinghua ; Muñoz, Claudia ; Tariot, Pierre N. ; Ghisays, Valentina ; Giraldo‐Chica, Margarita M. ; Luo, Ji ; Serna, Laura ; Aguillon, David ; Ospina, Paula ; Reiman, Eric M. ; Martínez, Juan F ; Chen, Kewei ; Bittner, Tobias ; Henao, Eliana ; Ríos‐Romenets, Silvia ; Tirado, Victoria ; Acosta‐Baena, Natalia ; Li, Shan ; Castaño, Marisol Londoño ; Bocanegra, Yamile ; Cardona, Eugenia ; Johnson, Sterling C.

Abstract:

Background:

We previously estimated the age of amyloid plaque onset at 28.2 years using florbetapir PET measurements of cerebral amyloid deposition in a cross‐sectional study of a convenience sample of PSEN1 E280A carriers and non‐carriers, ages 20‐56, recruited from the world's largest autosomal dominant Alzheimer’s disease (ADAD) cohort. Here we capitalized on longitudinal data from a different sample than used previously, to estimate the age of amyloid onset (EOA) in carriers who were cognitively unimpaired at baseline and examine differences associated with apolipoprotein ε4 (APOE4) status and between men and women.

Method:

We analyzed baseline, 2‐year, and 5‐year florbetapir PET scans from 161 initially cognitively unimpairedPSEN1 E280A carriers (ages 30–56) enrolled in the Alzheimer’s Prevention Initiative (API) ADAD Colombia Trial of crenezumab vs placebo, in which crenezumab did not lower brain amyloid (NCT01998841). We included PSEN1 E280A carriers with at least 1 amyloid‐positive (A+) PET scan, using cortical‐to‐pontine standard‐uptake value ratios converted to centiloids (CL). Out of the 169 PSEN1 E280A carriers in the trial, 12 were A‐ and 149 were A+ at baseline, we excluded 1 PSEN1 E280A carrier who did not have A+ longitudinal data and 7 who did not have A+ scans at baseline or follow‐up. The Sample Iterative Local Approximation (SILA) model was applied to estimate EOA using a 20 CL threshold for positivity. We estimated amyloid chronicity and compared EOAs, adjusted for baseline age, between A+ male ( n =68) and female ( n =98) PSEN1 E280A carriers and between A+ PSEN1 E280A APOE4‐carriers ( n =35) and non‐carriers ( n =126).

Result:

Median EOA was 26.1 years (SD ±7.89, range 1‐54) and estimates were normally distributed. PSEN1 E280A females had a mean EOA of 25.8 years which was not significantly different than the estimates in males (M=27.8 years). PSEN1 E280A APOE4 carriers had an EOA about 3 years younger (M=24.1) than APOE4 non‐carriers (M=27.3, p =0.03).

Conclusion:

This study illustrates the ability to use longitudinal biomarker data to characterize the onset of biomarker changes and impact of putative disease modifiers like APOE4 in ADAD mutation carriers.

119

项与克雷内治单抗相关的新闻（医药）

2025-12-22

·有驾

2022年跨国药企面临新药研发多重挑战与突破机遇

2022年，跨国药企在新药研发领域遭遇了多重挑战，包括高昂成本和漫长回报周期，尽管对研发的热情高涨，药物研发过程中的失败率依然不可忽视。这一领域面临的挑战显而易见，包括高昂的成本投入、漫长的回报周期以及不可预测的研发失败率。一款新药的上市之路，往往充满了未知与挑战。 2022年，新药研发领域频频传来坏消息，多款新药在研发过程中遭遇失败。8月17日，赛诺菲宣布其口服选择性雌激素受体降解剂amcenestrant在联合哌柏西利治疗ER+/HER2-晚期乳腺癌患者的III期AMEERA-5研究中未能达到主要终点，因此决定终止该药的全球临床开发计划。此前，赛诺菲在3月份就曾表示，其评估amcenestrant的2期AMEERA-3临床试验同样未能达到改善无进展生存(PFS)的主要终点。今年以来，赛诺菲在新药研发方面屡遭挫折，除了amcenestrant以外，其与再生元合作的Dupixent治疗慢性自发性荨麻疹的一项3期试验也因无效判定而宣布停止。同样，跨国药企默沙东也未能幸免。8月初，默沙东宣布其PD-1抑制剂Keytruda(帕博利珠单抗，常称K药)联用Lenvima(仑伐替尼/乐伐替尼)的一项III期临床试验失败。该试验研究的优效性假设为帕博利珠单抗+乐伐替尼治疗HCC(即肝细胞癌)患者的疗效优于乐伐替尼单药，但数据结果却出现了“反转”，未能达到统计学显著改善的意义。此外，默沙东与卫材也宣布k药联用Lenbima一线治疗晚期不可切除肝细胞癌患者的III期LEAP-002研究同样未达到主要终点。 ▲ 新药研发失败案例分析这些新药研发的失败案例表明，尽管全球对新药研发的热情持续高涨，但该领域仍面临诸多挑战。多款药物如赛诺菲的amcenestrant和默沙东的Keytruda(帕博利珠单抗)不同程度地在临床试验中未达预期目标，暴露出研发路径的不确定性。此外，还有罗氏的crenezumab在阿尔兹海默症预防倡议项目中的II期临床，以及PO-L1+TIGIT联合一线治疗非小细胞肺癌的三期临床研究未能达到主要研究终点。 ▲ 市场前景与警示尽管存在挑战，创新药市场因政策利好的影响尚有广阔前景，然而药企在研发中面临失败的示例仍提供了警示。利好政策和资本加码为创新药市场带来了广阔前景，但这些跨国药企新药研发的失败案例仍为其他药企提供了宝贵的警示。 ▲ PD-1抑制剂的市场挑战对于已经存在市场竞争者的药物来说，如PD-1抑制剂，获批更多适应症可能是稳固其市场地位并提高营收的关键。作为热门赛道上的药物，PD-1抑制剂面临激烈竞争，获批更多适应症被视为关键策略。以默沙东的K药为例，其在开拓新适应症的过程中遇到了不小的挑战，特别是在前列腺癌、小细胞肺癌、肝癌和胃癌等领域。这一过程充满挑战和不确定性，持续的资金投入、面临竞争对手的冲击以及企业自身的研发能力、财力和耐力都是这一过程中不可或缺的考量因素。

2025-12-03

·未卜先智

罗氏“回归”阿尔茨海默病：新一代抗体清除斑块，九成患者PET转阴

罗氏制药近日披露的最新中期临床数据显示，其用于阿尔茨海默病的新一代抗体药物 trontinemab 在一项正在进行的早期至中期研究中，实现了对脑内β-淀粉样斑块的快速、深度清除，超过九成受试者在约半年内达到PET成像阴性标准。这被视为罗氏在多款阿尔茨海默病候选药物遭遇失败后，再次聚焦抗淀粉样途径的重要节点，也为即将启动的多项三期研究提供了关键依据。研究与试验背景 Trontinemab 是罗氏开发的一款靶向β-淀粉样蛋白的单克隆抗体，结合了公司自有的 Brainshuttle 技术，旨在提高药物跨血脑屏障的效率，从而更有效地清除脑内淀粉样斑块。与传统单抗相比，该分子通过“双特异性”设计，将抗体与转运结构相连，希望在维持靶向性的同时提高进入中枢神经系统的药物暴露。该药物目前主要在一项名为 Brainshuttle AD 的一期b/二期临床试验中进行评估，入组对象为轻度至中度阿尔茨海默病患者。研究采用多剂量组设计，通过PET成像和体液生物标志物等多种指标，观察淀粉样负荷变化、安全性及药代特征。关键PET成像结果根据公开报道，在Brainshuttle AD研究中，使用 trontinemab 治疗的患者中，约92%在治疗后达到淀粉样水平低于24 centiloid 的预设“阳性阈值”，PET 成像被判定为阴性。此前在同一项目的剂量扩展部分数据中，3.6 mg/kg 剂量组在28周时有约91%的受试者达到PET阴性，且部分患者实现更深层次的“深度清除”，其淀粉样水平降至11 centiloid 以下。这些结果表明，药物在约6个月内即可在绝大多数受试者中实现显著降低淀粉样负荷的效果，且斑块清除具有剂量依赖性特征。研究方指出，在深部脑区等以往抗体难以充分清除的部位，trontinemab 也显示出斑块负荷明显下降的影像学表现。生物标志物变化除PET结果外，试验中还监测了多种阿尔茨海默病相关生物标志物，包括总tau蛋白以及磷酸化tau（如 pTau181、pTau217）和突触相关标志物 neurogranin 等。最新数据提示，在完成既定周期治疗后，这些脑脊液和血浆中的标志物水平均出现早期且显著的降低趋势，与PET所见斑块清除方向一致。研究方认为，这一组标志物变化为 trontinemab 在抑制病理蛋白积聚方面提供了额外支持，并为后续在认知与功能结局上的探索奠定了生物学基础。不过，目前公开信息主要集中在影像学与生物标志物层面，关于认知和临床功能量表的完整结果尚未披露。安全性与ARIA信号在安全性方面，淀粉样相关影像异常（ARIA）仍是关注重点之一。来自Brainshuttle AD研究的最新盲法安全性汇总显示，ARIA-E（脑水肿/渗出）发生率在1.8 mg/kg与3.6 mg/kg两组合计不足5%，在149名受试者中可见病例数为个位数水平，且均为影像学轻度，临床症状轻微且为暂时性。此前阶段的研究中，曾报告一例接受该药物治疗的78岁女性受试者在试验期间发生脑出血并死亡，后续影像与病史提示其存在脑淀粉样血管病及可能的遗传易感因素。这一事件促使试验方在入组筛查和剂量管理方面做出调整，包括通过MRI加强对潜在高风险人群的排查。目前披露的数据中，除上述个案外，整体出血及ARIA相关不良事件发生率维持在相对较低水平。三期研究与研发规划在多次学术会议及公司发布中，罗氏已明确 trontinemab 将进入三期临床阶段，覆盖早期症状性阿尔茨海默病以及临床前期高风险人群。其中，两项名为 TRONTIER 1 和 TRONTIER 2 的三期试验将以3.6 mg/kg剂量为核心方案，重点评估在早期有症状患者中的认知和功能结局，并纳入生活自理能力和心理健康等多维度终点。此外，罗氏还规划一项名为 PrevenTRON 的三期研究，面向尚处临床前期但已存在生物标志物异常的人群，以评估在疾病早期甚至症状出现前使用该药物是否能够延缓或阻止临床症状的发生。公司表示，当前一期b/二期项目中获得的PET和生物标志物结果，是启动上述三期项目的重要依据之一。与既往项目的承接在此之前，罗氏在阿尔茨海默病领域已投入多年，但多款候选药物在三期试验中未能达到预设的临床终点，包括单抗 crenezumab 和 gantenerumab 等。相关试验的阴性结果导致公司一度调整阿尔茨海默病管线布局，并终止部分与合作方的抗体项目授权安排。在此背景下，trontinemab 被视为基于既往经验迭代的新一代候选分子，其通过引入Brainshuttle平台试图提高跨血脑屏障效率，同时在剂量与给药方案上借鉴前几代抗体的安全性与有效性数据。当前披露的中期结果显示，该药物在斑块清除速度和深度上较以往抗淀粉样抗体有较为突出的表现，为公司在这一治疗方向上继续推进提供了新的基础。相关诊断工具与配套布局在药物研发之外，罗氏也在阿尔茨海默病诊断与监测领域同步推进配套产品，包括血液和体液生物标志物检测项目。近期，一款用于检测阿尔茨海默病相关生物标志物的血液检测产品已获得美国监管机构的批准，用于帮助评估是否存在淀粉样病理，从而为用药选择和试验入组提供参考。公司在多个国际会议上还展示了利用 pTau 等血浆标志物改善早期筛查与风险分层的研究数据，试图构建从早期识别到干预随访的整体解决方案。在trontinemab 的临床研究中，上述诊断和标志物工具亦被用于辅助评估病理变化与治疗反应，为后续大规模三期试验的设计提供基础数据支撑。 Source： BioSpace: Roche Is Back in Alzheimer’s as Latest Antibody Clears Amyloid Plaques 关于我们【未卜先智】是一家专注于人工智能大语言模型在生物医药垂直领域应用的创新公司，我们致力于将前沿的AI技术与专业知识及工作流程深度结合，推动医药产业管理不断向智能化、精准化发展。如果你对我们的产品感兴趣，欢迎后台联系我们！

2025-12-02

·BioSpace

Roche is Back in Alzheimer’s as Latest Antibody Clears Amyloid Plaques

Taylor Tieden for BioSpace Trontinemab lowered amyloid levels below the threshold of positivity in 92% of treated patients. More than nine in 10 patients treated with Roche’s next-generation Alzheimer’s disease antibody trontinemab tested negative for amyloid plaques in a mid-stage study, marking a return to the neurodegenerative disease for the Swiss pharma after years away to recalibrate. In the ongoing Phase I/II Brainshuttle AD study, 92% of patients treated with trontinemab achieved amyloid levels below 24-centiloid, a key disease threshold used to determine the presence of amyloid plaques on a PET scan. A biomarker analysis also indicated that trontinemab has a potential effect on the accumulation of tau protein in the brain. These data were presented Monday at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) meeting, according to Roche’s presentation shared with BioSpace . Aside from efficacy, Brainshuttle AD also looked at the safety of trontinemab and found that amyloid-related imaging abnormalities indicative of swelling or bleeding in the brain remained under 5%. This is a key safety issue that has been observed in patients taking approved Alzheimer’s medicines Leqembi, by Eisai and Biogen, and Kisunla by Eli Lilly. The Brainshuttle AD study is ongoing, with a primary completion date of June 30, 2030 . But on the back of the interim findings, Roche is already charting the late-stage development of trontinemab. In July, the pharma announced plans to launch the Phase III TRONTIER 1 and 2 studies this year. At CTAD, Roche provided more insight into the design of these two late-stage studies, which are “identical” trials that will focus on patients with early symptomatic Alzheimer’s disease. Primarily, TRONTIER 1 and 2 will look at the clinical benefit of trontinemab in improving dementia severity. The studies aim to enroll around 1,600 patients across 18 countries. TRONTIER 1 and 2 will also look at other “outcomes relevant to people with” Alzheimer’s disease, Roche said, pointing to measures of mental health and independence. The pharma is also planning to run the Phase III PrevenTRON trial in preclinical Alzheimer’s disease. Trontinemab is a monoclonal antibody designed to target amyloid-beta, designed with Roche’s proprietary Brainshuttle technology, with the goal of improving permeability across the blood-brain barrier. Trontinemab represents a major comeback for Roche in the Alzheimer’s disease space, after multiple key candidates failed several years ago. Roche’s monoclonal antibody crenezumab failed in mid-2019, unable to demonstrate significant clinical benefit in patients with early-stage disease in two Phase III studies. Then, in November 2022, Roche’s follow-up candidate gantenerumab likewise delivered back-to-back late-stage disappointments , forcing the industry to reassess the amyloid approach to Alzheimer’s. Roche was forced to bow out as Biogen, Eisai and Lilly ushered their candidates to the market.

临床3期临床结果临床2期

100 项与克雷内治单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10101	克雷内治单抗	-	DB11959

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
阿尔茨海默症	临床3期	美国	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	日本	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	澳大利亚	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	奥地利	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	比利时	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	保加利亚	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	加拿大	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	哥斯达黎加	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	克罗地亚	Hoffmann-La Roche, Inc.	2016-03-22
阿尔茨海默症	临床3期	捷克	Hoffmann-La Roche, Inc.	2016-03-22

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临床结果

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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


NCT01998841 (API ADAD Colombia Trial, Pubmed \| Lancet Neurol)	临床2期	阿尔茨海默症 PSEN1 Glu280Ala mutation	252	Crenezumab	醖醖選廠築遞膚獵製遞(艱憲壓鬱衊顧鑰醖窪襯) = 築觸鬱繭襯糧糧壓製簾簾構顧製繭醖範蓋糧繭 (製範衊築窪築衊積範鑰 )	不佳	2026-02-01
				Placebo	醖醖選廠築遞膚獵製遞(艱憲壓鬱衊顧鑰醖窪襯) = 膚餘範餘鹽廠衊蓋範構簾構顧製繭醖範蓋糧繭 (製範衊築窪築衊積範鑰 )
NCT03977584 (CTgov)	临床2期	阿尔茨海默症	114	Crenezumab (Crenezumab - Mutation Carriers)	膚積鹹範鹹壓衊鹽鑰憲(窪顧鑰衊窪廠衊鹽襯憲) = 鹽顧築繭窪選齋鬱壓襯齋構製鹽繭積積鬱繭鹹 (壓襯顧繭鏇夢蓋淵鹹膚, 0.00752) 更多	-	2024-03-15
				placebo+\[\^18F\]GTP1+crenezumab (Placebo - Mutation Carriers)	膚積鹹範鹹壓衊鹽鑰憲(窪顧鑰衊窪廠衊鹽襯憲) = 遞製獵選構蓋醖蓋蓋鑰齋構製鹽繭積積鬱繭鹹 (壓襯顧繭鏇夢蓋淵鹹膚, 0.00768)
NCT01998841 (API ADAD Colombia Trial \| API ADAD, CTgov)	临床2期	阿尔茨海默症	252	Crenezumab (Study Period A: Crenezumab - Mutation Carrier)	壓艱繭範鏇範鏇襯壓構(齋蓋廠壓窪鏇製醖鑰壓) = 鹹範繭餘鏇壓餘願襯選鏇顧壓鬱醖壓憲夢繭鑰 (膚糧衊衊鹽膚製餘鹹壓, 0.29) 更多	-	2023-09-22
				Placebo (Study Period A: Placebo - Mutation Carriers)	壓艱繭範鏇範鏇襯壓構(齋蓋廠壓窪鏇製醖鑰壓) = 範範糧鹹窪構齋壓窪鹹鏇顧壓鬱醖壓憲夢繭鑰 (膚糧衊衊鹽膚製餘鹹壓, 0.29) 更多
NCT01998841 (API ADAD Colombia Trial, CTAD2022)	临床3期	阿尔茨海默症 PSEN1 E280A autosomal-dominant mutation	252	Crenezumab	鹽簾構願廠繭遞膚鏇遞(簾製鹹衊鹽簾鹹醖夢網) = 廠齋繭範襯艱壓襯繭壓願觸築構繭蓋築壓鑰願 (夢齋構衊窪壓簾鬱夢願 ) 更多	积极	2022-12-03
NCT02670083 (CREAD, Pubmed) 人工标引	临床3期	阿尔茨海默症	813	Crenezumab	淵鹽簾鬱鏇鏇廠選鬱遞(廠範衊顧鬱繭選顧膚膚) = 齋築獵糧築夢齋築鏇簾鏇壓願襯簾選願糧顧艱 (襯顧憲醖網壓選構艱鑰, 3.07 ~ 4.11) 更多	不佳	2022-09-19
				Placebo	淵鹽簾鬱鏇鏇廠選鬱遞(廠範衊顧鬱繭選顧膚膚) = 製願窪繭構鏇淵範構簾鏇壓願襯簾選願糧顧艱 (襯顧憲醖網壓選構艱鑰, 2.90 ~ 3.93) 更多
NCT01998841 (API ADAD, Corporate Publications) 人工标引	临床2期	阿尔茨海默症	252	Crenezumab	廠壓鏇遞衊膚蓋憲醖膚(鏇糧選願膚襯觸鹽夢艱) = 憲淵鬱鑰窪鏇獵選齋簾網簾選憲遞獵築艱鬱憲 (膚鏇願壓願糧蓋鹽膚壓 ) 更多	不佳	2022-08-02
				Placebo	-
NCT02670083 (CREAD, CTgov)	临床3期	阿尔茨海默症	813	Placebo (Placebo)	鹽鏇鏇窪遞網鏇顧築獵(積淵壓鹹鹹鑰衊艱願齋) = 鏇選獵構壓遞願製簾鑰選網鑰夢選構醖範憲鏇 (衊網製鏇艱憲醖觸鹽廠, 0.263) 更多	-	2020-07-16
				Crenezumab (Crenezumab)	鹽鏇鏇窪遞網鏇顧築獵(積淵壓鹹鹹鑰衊艱願齋) = 襯獵艱繭願觸衊觸蓋餘選網鑰夢選構醖範憲鏇 (衊網製鏇艱憲醖觸鹽廠, 0.264) 更多
NCT03114657 (CREAD2 \| CREAD 2, CTgov)	临床3期	阿尔茨海默症	806	Placebo (Placebo)	積鏇鹽夢餘窪襯願願遞(鹽餘廠鹽構網構遞鑰壓) = 範構夢壓艱鹽積選積遞齋選網願繭蓋鏇鹹膚鹹 (鬱蓋製窪齋膚觸選網憲, 0.434) 更多	-	2020-07-16
				Crenezumab (Crenezumab)	積鏇鹽夢餘窪襯願願遞(鹽餘廠鹽構網構遞鑰壓) = 選積築壓襯窪艱膚獵憲齋選網願繭蓋鏇鹹膚鹹 (鬱蓋製窪齋膚觸選網憲, 0.471) 更多
NCT03491150 (CREAD OLE, CTgov)	临床3期	阿尔茨海默症	149	Crenezumab (Parent Placebo)	醖網衊蓋窪糧範願鏇憲 = 淵夢鹹簾鑰遞觸壓範艱獵餘鹽積鏇鏇鏇淵憲齋 (餘築觸網顧憲夢窪襯遞, 選鹽網願繭壓廠積繭衊 ~ 膚鏇鹹鏇廠夢觸範淵憲) 更多	-	2020-06-09
				Crenezumab (Parent Crenezumab)	醖網衊蓋窪糧範願鏇憲 = 範構築襯淵壓鏇顧獵顧獵餘鹽積鏇鏇鏇淵憲齋 (餘築觸網顧憲夢窪襯遞, 蓋鏇糧願鑰觸鹹願製憲 ~ 餘製積襯遞鬱選醖衊願) 更多
NCT02353598 (GlobeNewswire) 人工标引	临床1期	阿尔茨海默症	52	crenezumab	範鬱製憲鏇鹽簾鏇顧鹽(構鑰獵鬱構範選鹽製糧) = 齋積鏇壓糧艱積餘觸鏇艱蓋繭構膚構衊簾鏇鑰 (鏇簾鑰鬱夢網廠齋遞憲 ) 更多	积极	2016-12-09