Synaptic Therapy Alzheimer's Research Trial (START): A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease Over 18 Months.

This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo in participants diagnosed with early Alzheimer's disease.

开始日期2023-06-28

申办/合作机构

Cognition Therapeutics, Inc.

[+1]

NCT05893537

/ Active, not recruiting临床2期

A Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Efficacy and Safety of Oral CT1812 in Participants with Geographic Atrophy (GA) Secondary to Dry Age-Related Macular Degeneration (AMD).

This is a Phase 2, prospective, multicenter, randomized, double-masked, placebo-controlled 104-week study to assess the efficacy, safety, and tolerability of orally delivered CT1812 compared to placebo in participants with GA associated with dry AMD.

开始日期2023-06-16

申办/合作机构

Cognition Therapeutics, Inc.

NCT05225415

/ Completed临床2期

A Randomized, Double-blind, Placebo-controlled, Phase 2, 6-month Study to Evaluate the Safety, Tolerability and Exploratory Efficacy of CT1812 in Subjects with Mild to Moderate Dementia with Lewy Bodies

Multi-center, randomized, double-blind, placebo-controlled, 6- month study in subjects with mild to moderate Dementia with Lewy Bodies.

开始日期2022-05-19

申办/合作机构

Cognition Therapeutics, Inc.

[+1]

100 项与 CT-1812 相关的临床结果

登录后查看更多信息

100 项与 CT-1812 相关的转化医学

登录后查看更多信息

100 项与 CT-1812 相关的专利（医药）

登录后查看更多信息

项与 CT-1812 相关的文献（医药）

2024-12-01·JPAD-Journal of Prevention of Alzheimers Disease

A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer's Disease

Article

作者: Grundman, M ; de Haan, W ; Scheijbeler, E ; Scheltens, P ; Grundman, M. ; de Haan, W. ; Catalano, S ; Hamby, M E ; Caggiano, A.O. ; Hamby, M.E. ; Caggiano, A O ; Catalano, S. ; Vijverberg, E ; Scheijbeler, E. ; Scheltens, P. ; Vijverberg, E.

BACKGROUND:

CT1812 is a first-in-class, sigma-2 receptor ligand, that prevents and displaces binding of amyloid beta (Aβ) oligomers. Normalization of quantitative electroencephalography (qEEG) markers suggests that CT1812 protects synapses from Aβ oligomer toxicity.

OBJECTIVES:

Evaluate CT1812 impact on synaptic function using qEEG measurements.

DESIGN:

Phase 2, randomized, double-blind, placebo-controlled, 4-week crossover study.

SETTING:

VU University Medical Center and Brain Research Center Amsterdam, The Netherlands.

PARTICIPANTS:

Adults with mild or moderate Alzheimer's disease (AD).

INTERVENTION:

A daily 300 mg dose of CT1812 or placebo for 4 weeks.

MEASUREMENTS:

A resting-state, eyes closed qEEG assessment occurred on Day 1 and on Day 29 of Treatment Periods 1 and 2, and at follow-up. The primary endpoint was global relative theta power (4-8 Hz), along with secondary EEG measures including global alpha corrected Amplitude Envelope Correlation (AEC-c). Cognitive and functional assessments, fluid biomarkers, and safety and tolerability were assessed.

RESULTS:

16 patients were randomized, and 15 completed. A non-significant (p=0.123) but consistent reduction occurred in global relative theta power and in relative theta power in frontal, temporal, parietal, occipital and central (p<0.006) brain regions with CT1812. A nominally significant (p=0.034) improvement was observed in global alpha AEC-c. Adverse events occurred in 11 patients with CT1812 and 6 with placebo - most commonly nausea, diarrhea, and procedural headache. No severe or serious AEs, deaths or discontinuations were reported.

CONCLUSION:

CT1812 improved established EEG markers of spontaneous brain activity (spectral power, functional connectivity) in patients with mild-to-moderate AD, suggesting improved neuronal/synaptic function within a 4-week timespan.

2024-11-01·CLINICAL THERAPEUTICS

Clinical Update on an Anti-Alzheimer Drug Candidate CT1812: A Sigma-2 Receptor Antagonist

Review

作者: Bajpai, Ankit ; Singh, Ranjit ; Bansal, Ranju ; Dar, Zahid Ahmad ; Kaur, Guramrit

PURPOSE:

This review article summarizes the progress and latest findings related to the investigational drug candidate CT1812, which is currently in phase 2 clinical trials for Alzheimer's disease (AD). The article outlines the development of this promising molecule and provides insights into its mechanism of action as sigma-2 receptor (S2R) antagonist along with the positive outcomes of various clinical trials. Literature mentioning AD therapeutics that specifically target amyloid-beta (Aβ) oligomers is limited even though these oligomers are established as the most neurotoxic forms of the Aβ protein. This timely article highlights the potential of CT1812 as a breakthrough in AD therapeutics, providing a new avenue for addressing the neurotoxic forms of Aβ and advancing the field toward a potential cure for AD.

METHODS:

The literature includes articles searched from PubMed and Google Scholar along with a comprehensive discussion of all the clinical research trials undertaken for CT1812. The review includes 12 clinical trials; of the total citations identified, 10 have been used to support the results of published trials.

FINDINGS:

The positive outcomes in the multiple clinical trials conducted on CT1812 indicate the emergence of an effective and promising drug candidate for AD. The article mentions a gap in the literature regarding AD therapeutics specifically targeting Aβ oligomers, which reveals lack of established treatments addressing Aβ oligomers, making the novel approach of CT1812 noteworthy.

IMPLICATIONS:

Clinical treatments available today provide symptomatic relief, however, any drug providing a potential cure for AD remains an unanswered question. S2Rs mediated oligomer binding in addition to synaptic toxicity suggest the potential usefulness of CT1812 in AD treatment. Efficacy and safety of CT1812 in further clinical trials could represent a significant advancement in the field, offering a potential treatment that goes beyond the symptomatic relief and aimed at addressing the core mechanisms associated with AD.

2024-10-18·JOURNAL OF ALZHEIMERS DISEASE

CT1812, a Small Molecule Sigma-2 Receptor Antagonist for Alzheimer’s Disease Treatment: A Systematic Review of Available Clinical Data

Review

作者: Pappolla, Miguel A. ; Perry, George ; Zhu, Xiongwei ; Thitilertdecha, Premrutai ; Brimson, James Michael ; Plascencia-Villa, German ; Sorensen, Aaron A. ; Moreira, Paula I. ; Galimberti, Daniela ; Avila, Jesus

Background: Alzheimer’s disease (AD) is of growing concern worldwide as the demographic changes to a more aged population. Amyloid-β (Aβ deposition is thought to be a key target for treating AD. However, Aβ antibodies have had mixed results, and there is concern over their safety. Studies have shown that the sigma-2 receptor (σ-2R)/TMEM97 is a binding site for Aβ oligomers. Therefore, targeting the receptor may be beneficial in displacing Aβ oligomers from the brain. CT1812 is a σ-2R/TMEM97 antagonist that is effective in preclinical studies of AD and has been entered into clinical trials. Objective: The objective of this study was to systematically review the safety and efficacy of CT1812 for the treatment of AD. Methods: Between June and August 2023, we searched the primary literature (PubMed, Scopus, Google Scholar, etc.) and clinical trials databases (http://www.clinicaltrails.gov). The extracted data is evaluated within this manuscript. Results: CT1812 is relatively safe, with only mild adverse events reported at doses up to 840 mg. CT1812 can displace Aβ in the clinical studies, in line with the preclinical data. Studies have investigated brain connectivity and function in response to CT1812. However, the cognitive data is still lacking, with only one study including cognitive data as a secondary outcome. Conclusions: CT1812 safely works to displace Aβ however, whether this is enough to prevent/slow the cognitive decline seen in AD remains to be seen. Longer clinical trials are needed to assess the efficacy of CT1812; several trials of this nature are currently ongoing.

125

项与 CT-1812 相关的新闻（医药）

2025-01-23

·PRNewswire

70+ Key Companies Advancing in Dry Age-Related Macular Degeneration Clinical Trial Therapeutic Space | DelveInsight

Dry macular degeneration is a common eye disorder among people aged above 50 years. It causes blurred or reduced central vision due to thinning of the macula. The macula is the part of the retina responsible for clear vision in a direct line of sight. The pharmaceutical industry is increasingly focused on developing pathway-based therapies for dry AMD, with promising treatments like ALK-001 and LBS-008 in trials, though a combination approach may be needed to fully inhibit disease progression. LAS VEGAS, Jan. 23, 2025 /PRNewswire/ -- DelveInsight's ' Dry Age-Related Macular Degeneration Pipeline Insight 2025 ' report provides comprehensive global coverage of pipeline dry AMD therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the dry AMD pipeline domain. Key Takeaways from the Dry Age-Related Macular Degeneration Pipeline Report DelveInsight's dry AMD pipeline report depicts a robust space with 70+ active players working to develop 80+ pipeline therapies for dry AMD treatment. Key dry AMD companies such as Alkeus Pharmaceuticals, Dobecure, Belite Bio, Cognition Therapeutics, Aviceda Therapeutics, Stealth BioTherapeutics, Allergo Ophthalmics, Annexon, Inc., Johnson & Johnson, InflammX Therapeutics, Lineage Cell Therapeutics, Ionis Pharmaceuticals, Evergreen Therapeutics, Inc., Alexion, Luxa Biotechnology, Astellas Pharma, OliX Pharmaceuticals, Hoffmann-La Roche, Boehringer Ingelheim, Eyevensys and others are evaluating new dry AMD drugs to improve the treatment landscape. Promising dry AMD pipeline therapies such as ALK-001, Etamsylate, Tinlarebant (LBS-008), CT1812, AVD-104, Elamipretide, Risuteganib, ANX 007, JNJ 81201887, Xiflam, OpRegen, IONIS-FB-LRx, EG-301, ALXN2040, RPESC-RPE-4W, MA09-hRPE, OLX301A, RO7303359, BI 771716, EYS 611 and others are under different phases of dry AMD clinical trials. In December 2024, Galimedix Therapeutics announced the initiation of its Phase II eDREAM study to assess the safety and efficacy of GAL-101 eye drops in patients with dry age-related macular degeneration. In December 2024, Ocugen, Inc. announced that the Data and Safety Monitoring Board (DSMB) for the OCU410 ArMaDa clinical trial recently convened and approved continuation of the second phase of the Phase 1/2 study. OCU410 (AAV5-hRORA) is a novel modifier gene therapy candidate being developed for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD). In November 2024, Ocugen, Inc. announced positive preliminary efficacy and safety data from the Phase I dose-escalation portion of the Phase 1/2 OCU410 ArMaDa clinical trial for geographic atrophy (GA), secondary to dry age-related macular degeneration (dAMD). Key findings include: no drug-related serious adverse events, reduced lesion growth, preservation of retinal tissue, and most importantly there was a positive effect on the functional visual measure of low luminance visual acuity (LLVA). In October 2024, Eyestem Research, focused on creating scalable cell therapies for incurable diseases, had announced a positive outcome of the Drug Safety Monitoring Board (DSMB) review for the first cohort of its Phase one trial to treat Geographic Atrophy secondary to Dry Age-related Macular Degeneration, marking a milestone for Indian science and medical research. In September 2024, Stealth BioTherapeutics Inc. announced the presentation of new bevemipretide (SBT-272) preclinical data demonstrating topical ocular delivery to the retina with protective effects observed in models of AMD. In June 2024, Stealth BioTherapeutics Inc. announced that it has enrolled and dosed its first patient in the ReNEW trial as part of its Phase III clinical program for elamipretide in patients with dry age-related macular degeneration (dry AMD). The program consists of the two Phase III trials, ReNEW and ReGAIN. Both trials will evaluate the efficacy, safety, and pharmacokinetics of daily subcutaneous injections of elamipretide in participants with dry AMD. In April 2024, Eyestem received approval from India's Central Drugs Standards Control Organisation (CDSCO) to commence human trials for Eyecyte RPE, a potential treatment for geographic atrophy arising from dry age-related macular degeneration (AMD). Request a sample and discover the recent advances in dry AMD treatment drugs @ Dry Age-Related Macular Degeneration Pipeline Report The dry AMD pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage dry AMD drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the dry AMD clinical trial landscape. Dry Age-Related Macular Degeneration Overview Age-related macular degeneration (AMD) is one of the top four causes of blindness in older adults and the leading cause of irreversible blindness in developed countries. Around 170 million people globally are affected by AMD, making it the third most common cause of vision loss worldwide. Dry AMD typically progresses slowly, but wet AMD can cause severe visual impairment within days or weeks of onset. In the early stages of AMD, there are no noticeable symptoms, though an ophthalmologist can detect drusen before symptoms arise. Some individuals experience slight vision changes during the intermediate stage, but many remain symptom-free. Others may notice dark or grey spots in their central vision or have difficulty transitioning from bright to dim lighting. Clinicians currently use various imaging techniques to monitor changes in the retina, retinal pigment epithelium (RPE), and choroid, including fundus exams, color fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), and infrared reflectance imaging. Over the past two decades, OCT has significantly advanced the early detection, monitoring, and treatment assessment of dry AMD. Modern spectral-domain OCT (SD-OCT) systems provide detailed cross-sectional and volumetric views of the retina, enabling clinicians to visualize, measure, and monitor retinal layers, RPE, hyperreflective foci, geographic atrophy (GA), and drusen. While SD-OCT remains the standard of care, emerging technologies like polarization-sensitive OCT (PS-OCT), which offers tissue-selective imaging, may revolutionize AMD research and clinical practices. Currently, no approved treatments exist for dry AMD. Management involves regular monitoring, timely detection of visual deterioration, appropriate rehabilitation, and early identification of choroidal neovascularization (CNV). Research is underway to explore therapeutic strategies to prevent AMD, slow its progression, or restore vision. Potential treatments include lifestyle and behavioral changes, age-related eye disease study (AREDS) supplements, visual cycle modulators, anti-inflammatory agents, complement inhibitors, gene therapy, cell-based therapies, and approaches to reduce toxic by-products. Find out more about dry AMD treatment drugs @ Drugs for Dry Age-Related Macular Degeneration Treatment A snapshot of the Dry Age-Related Macular Degeneration Pipeline Drugs mentioned in the report: Learn more about the emerging dry AMD pipeline therapies @ Dry Age-Related Macular Degeneration Clinical Trials Dry Age-Related Macular Degeneration Therapeutics Assessment The dry AMD pipeline report proffers an integral view of the dry AMD emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Dry Age-Related Macular Degeneration Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Dimerisation inhibitors, Vitamin A replacements, RBP4 protein inhibitors, Sigma-2 receptor antagonists, Complement factor H stimulants, Macrophage inhibitors, Cell replacements, RNA interference, Key Dry Age-Related Macular Degeneration Companies: Alkeus Pharmaceuticals, Dobecure, Belite Bio, Cognition Therapeutics, Aviceda Therapeutics, Stealth BioTherapeutics, Allergo Ophthalmics, Annexon, Inc., Johnson & Johnson, InflammX Therapeutics, Lineage Cell Therapeutics, Ionis Pharmaceuticals, Evergreen Therapeutics, Inc., Alexion, Luxa Biotechnology, Astellas Pharma, OliX Pharmaceuticals, Hoffmann-La Roche, Boehringer Ingelheim, Eyevensys and others Key Dry Age-Related Macular Degeneration Pipeline Therapies: ALK-001, Etamsylate, Tinlarebant (LBS-008), CT1812, AVD-104, Elamipretide, Risuteganib, ANX 007, JNJ 81201887, Xiflam, OpRegen, IONIS-FB-LRx, EG-301, ALXN2040, RPESC-RPE-4W, MA09-hRPE, OLX301A, RO7303359, BI 771716, EYS 611 and others. Dive deep into rich insights for new drugs for dry AMD treatment, visit @ Dry Age-Related Macular Degeneration Drugs Table of Contents For further information on the dry AMD pipeline therapeutics, reach out @ Dry Age-Related Macular Degeneration Treatment Drugs Related Reports Dry Age-Related Macular Degeneration Market Dry Age-Related Macular Degeneration Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key dry AMD companies including Alkeus Pharmaceuticals, Belite Bio, Aviceda Therapeutics, Johnson & Johnson Innovative Medicine, Allegro Ophthalmics, Lineage Cell Therapeutics (CellCure Neurosciences), Roche, Cognition Therapeutics, Stealth BioTherapeutics, Evergreen Therapeutics, Annexon Biosciences, NGM Biopharmaceuticals, AstraZeneca, Alexion Pharmaceuticals, Ionis Pharmaceuticals, Novartis, Regenerative Patch Technologies, among others. Dry Age-related Macular Degeneration Epidemiology Forecast Dry Age-related Macular Degeneration Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted dry AMD epidemiology in the 7MM, i.e., the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan. Age-related Macular Degeneration Market Age-related Macular Degeneration Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key AMD companies including Regeneron Pharmaceuticals, Novartis, Roche, Opthea Limited, Kodiak Sciences Inc., REGENXBIO, Alkahest Inc, Graybug Vision, Ribomic USA Inc, Outlook Therapeutics, Inc., Unity Biotechnology, Inc, PanOptica, Inc., Clearside Biomedical, Alexion Pharmaceuticals, AstraZeneca, Evergreen Therapeutics, Alkeus Pharmaceuticals, Stealth BioTherapeutics, CellCure Neurosciences, Regenerative Patch Technologies, Allegro Ophthalmics, Annexon Biosciences, NGM Biopharmaceuticals, Ionis Pharmaceuticals, Apellis Pharmaceuticals, Iveric Bio, Gyroscope Therapeutics, Luxa Biotechnology, Gemini Therapeutics , among others. Wet Age-related Macular Degeneration Market Wet Age-related Macular Degeneration Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Wet Age-related Macular Degeneration companies including EyePoint Pharmaceuticals, Inc., AbbVie, Caregen Co. Ltd., Exegenesis Bio, Shanghai Henlius Biotech, Skyline Therapeutics, 4D Molecular Therapeutics, Ocugenix Corporation, Adverum Biotechnologies, Inc., Ashvattha Therapeutics, Inc., AiViva BioPharma, Inc., Ocular Therapeutix, Inc., Clearside Biomedical, Inc., Hoffmann-La Roche, Kyowa Kirin, Inc., Opthea Limited, AffaMed Therapeutics Limited, EyeBiotech Ltd., Novartis , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期临床3期临床2期

2024-12-19

·药明康德

认知指标改善超90%！小分子疗法痴呆症研究达主要终点

▎药明康德内容团队编辑日前，Cognition Therapeutics公布了探索性临床2期SHIMMER研究的主要结果。分析显示，其在研小分子CT1812在路易体痴呆（DLB）患者的行为、功能、认知和运动指标上均具有显著的治疗效果。详细数据将在2025年1月的国际路易体痴呆会议（ILBDC）上公布。根据这些积极结果，Cognition Therapeutics将加速推动CT1812进入后期临床试验。路易体痴呆是继阿尔茨海默病之后第二常见的痴呆类型。这种疾病的病因被认为是α-突触核蛋白积聚所造成，这些蛋白聚集形成的路易小体存在于脑神经元内。DLB是一种全身性疾病，会影响自主神经、消化、认知和运动系统的生物学过程。疾病初期可能出现不同症状，包括日常警觉水平波动、幻觉、妄想、运动障碍以及快速眼动睡眠行为障碍（表现为在睡眠期间演绎梦境）。目前针对这些症状的治疗多为标示外治疗，尚无获批的疾病修饰疗法。 SHIMMER研究是一项探索性双盲、安慰剂对照的2期临床试验，共招募130名轻中度DLB患者。研究期间，研究人员使用神经精神病学清单（NPI）来测量患者的幻觉、焦虑和妄想的变化；使用蒙特利尔认知评估（MoCA）和认知药物研究测验组（CDR）来评估患者的认知表现；使用临床波动评估（CAF）来测量认知波动的频率和持续时间；以及使用统一帕金森氏症评定量表（MDS-UPDRS）第3部分对帕金森综合征进行客观评估。 ▲CT1812组患者在多项认知、行为、运动、功能的下降上均获得减缓（图片来源：参考资料[2]）该研究共随机分配130名患者接受每日一次两种口服剂量的CT1812或安慰剂治疗，持续6个月。结果表明，该研究达到了安全性和耐受性的主要终点。数据显示，与安慰剂组相比，接受CT1812治疗的DLB患者在行为、功能、认知和运动指标上均表现出显著改善。尤其值得注意的是，CT1812治疗组的NPI总评分下降速度放缓了82%，其中焦虑、幻觉和妄想的改善尤为显著。此外，护理人员的压力显著减少，表明药物对患者的日常生活产生了积极影响。与安慰剂组相比，CT1812治疗组在所有三项认知指标上的下降幅度均显著放缓，其中注意力波动下降了91%。 ▲CT1812显著改善患者的注意力（图片来源：参考资料[2]） CT1812是一种在研的口服小分子寡聚物拮抗剂，可穿透血脑屏障，并选择性地与σ-2受体复合物结合。该复合物参与调节多种关键细胞过程，但这些过程易受β淀粉样蛋白（Aβ）或α-突触核蛋白寡聚物毒性相互作用、氧化应激及其他致病因素的干扰。由此导致的突触损伤可能逐渐发展为突触功能丧失，从而表现为认知障碍和疾病进展。目前，CT1812还在其他研究中接受评估，包括针对早期阿尔茨海默病患者的START研究，以及针对由干性年龄相关性黄斑变性（GA）引起的地理性萎缩患者的MAGNIFY研究。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Cognition Therapeutics Announces Positive Results in Phase 2 Study of CT1812 in Dementia with Lewy Bodies. Retrieved December 18, 2024 from https://ir.cogrx.com/press_releases/cognition-therapeutics-announces-positive-results-in-phase-2-study-of-ct1812-in-dementia-with-lewy-bodies/ 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床2期

2024-11-28

·医药魔方

新药研发“死亡谷”再埋枯骨

新药研发“死亡谷”又有项目被埋了。最近一个月，多款靶向治疗阿尔茨海默病的创新药披露最新进展，喜忧参半。近期披露进展的阿尔茨海默病新药其中，Simufilam和AL002针对的靶点较为新颖。细丝蛋白A（FLNA）本是细胞内正常存在的一种支架蛋白，在Aβ蛋白的毒性形式Aβ42影响下可发生错构，从而转变为Aβ蛋白的“帮凶”，导致磷酸化tau蛋白和炎症因子产生，使大脑神经元受损；髓样细胞触发受体（TREM2）是一种跨膜蛋白，参与调控大脑的小胶质细胞的吞噬作用和炎症反应。在病理状态下，TREM2无法与Aβ蛋白结合，导致小胶质细胞无法清除Aβ蛋白，使大脑神经元受损。因而，靶向FLNA和TREM2被认为是治疗阿尔茨海默病的可行策略。遗憾的是，Simufilam和AL002双双失败，而且结果相当惨烈，无论是主要终点还是次要终点、生物标志物相关终点均未达到。 III期ReThink-ALZ研究结果显示，相比于安慰剂组，Simufilam组患者的阿尔茨海默病评定量表-认知功能子量表（ADAS-Cog12）评分（+2.8分 vs +3.2分，Δ=-0.39分，P=0.43）和阿尔茨海默病协作研究-日常生活能力量表（ADCS-ADL）评分（-3.3分 vs -3.8分，Δ=0.51分，P=0.40）并未显著改善。 II期INVOKE-2研究结果显示，相比于安慰剂组，AL002组患者的临床痴呆评定量表总和（CDR-SB）分数未显著改善。而Blarcamesine和CT1812针对的靶点已经被研究得较为透彻。 σ1受体（σ1R）是一种位于内质网线粒体相关膜表面的分子伴侣蛋白，参与记忆功能发挥和神经保护等过程；σ2受体（σ2R）是一种内质网驻留膜蛋白，参与Aβ低聚物清除和神经元细胞的凋亡过程；毒蕈碱乙酰胆碱受体（mAChR）可与神经递质乙酰胆碱结合，帮助机体发挥学习和记忆功能。研究表明，Aβ蛋白会对这些受体介导的生理过程产生负面影响，导致阿尔茨海默病的发生发展，因而靶向激活σ1R、拮抗σ2R和激活mAChR具备治疗阿尔茨海默病的潜力。作为σ1R/mAChR激动剂的Blarcamesine和作为σ2R拮抗剂的CT1812确实通过了临床研究的考验。 II/III期AD-004研究结果显示，相比于安慰剂组，Blarcamesine组患者的ADAS-Cog13评分显著改善（Δ=-2.027，P=0.008）。 II期SHINE研究结果显示，在意向性治疗（ITT）人群中，CT1812组与安慰剂组患者的ADAS-Cog11评分暂无显著性差异（P=0.30）。不过，在磷酸化tau-217蛋白水平低于中位数（1.0pg/mL）的人群中，相比于安慰剂组，CT1812组患者的ADAS-Cog11评分显著改善（P=0.06）。基于上述结果，两款药物的下一步开发计划均已明朗——Anavex Life Sciences向欧洲药品监督管理局提交了Blarcamesine用于治疗阿尔茨海默病的上市申请，Cognition Therapeutics将与FDA讨论CT1812的注册性III期临床试验设计方案。 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。

临床结果临床2期临床3期

100 项与 CT-1812 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
干性年龄相关性黄斑病变	临床2期	美国	Cognition Therapeutics, Inc.	2023-06-16
地图样萎缩	临床2期	美国	Cognition Therapeutics, Inc.	2023-06-16
路易体病	临床2期	美国	Cognition Therapeutics, Inc.	2022-05-19
阿尔茨海默症	临床2期	美国	Cognition Therapeutics, Inc.	2018-10-10
阿尔茨海默症	临床2期	澳大利亚	Cognition Therapeutics, Inc.	2018-10-10
阿尔茨海默症	临床2期	捷克	Cognition Therapeutics, Inc.	2018-10-10
阿尔茨海默症	临床2期	荷兰	Cognition Therapeutics, Inc.	2018-10-10
阿尔茨海默症	临床2期	西班牙	Cognition Therapeutics, Inc.	2018-10-10
认知功能障碍	临床1期	澳大利亚	Cognition Therapeutics, Inc.	2015-09-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03507790 (SHINE, GlobeNewswire) 人工标引	临床2期	阿尔茨海默症	153	CT1812	願網糧範壓鬱選憲鏇築(觸網築簾醖構獵顧願範) = ADAS-Cog 11 scores showed 95% slowing of decline. 壓積顧築積餘憲鬱壓選 (願積觸築餘糧鹽鏇蓋鹽 ) 更多	积极	2024-10-29
				Placebo
NCT05225389 (COG0108, CTgov)	临床1期	阿尔茨海默症	8	CT1812+[14C]-CT1812	構憲繭窪糧憲壓鏇鏇築(窪願簾醖遞糧糧網選顧) = 鹹醖夢製遞鏇築鹹鏇鹽淵網淵蓋襯簾範膚糧鏇 (鏇鹽積餘醖簾鹽窪築襯, 糧鑰廠蓋製膚鏇鏇鏇製 ~ 繭蓋選窪襯廠鹽築繭鏇) 更多	-	2023-07-21
NCT03493282 (SPARC, Corporate Publications) 人工标引	临床1/2期	阿尔茨海默症	23	CT 1812	廠夢鬱壓淵鹽獵壓製觸(憲鹽鏇範鏇顧淵齋餘壓) = SAE has not been reported. 餘繭遞蓋鹽簾繭鏇簾夢 (積觸觸壓構窪衊鹽願簾 ) 更多	积极	2022-08-04
				Placebo