A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PMN310 in Patients With Early Alzheimer's Disease

This Phase 1b study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple IV infusions of PMN310 in patients with early Alzheimer's disease.

开始日期2024-12-13

申办/合作机构

ProMIS Neurosciences, Inc.

NCT06105528

/ Completed临床1期

A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PMN310 Infusions in Healthy Volunteers

This first in human Phase 1a clinical trial will evaluate the safety, tolerability, and pharmacokinetics of a single IV infusion of PMN310 in healthy volunteers.

开始日期2023-11-18

申办/合作机构

ProMIS Neurosciences, Inc.

100 项与 PMN-310 相关的临床结果

登录后查看更多信息

100 项与 PMN-310 相关的转化医学

登录后查看更多信息

100 项与 PMN-310 相关的专利（医药）

登录后查看更多信息

项与 PMN-310 相关的文献（医药）

2025-12-01·Alzheimers & Dementia

PRECISE‐AD, A Phase 1b, Double‐Blind, Placebo‐Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PMN310 in Patients with Early Alzheimer's Disease

Article

作者: Cashman, Neil ; Luca, Wendy ; Malefant, Gavin ; Altstiel, Larry D ; Lamendola, Misty ; Gibbs, Ebrima ; Kaplan, Johanne

Abstract:

Background:

Toxic Aβ oligomers (AβO) are implicated in the progression of Alzheimer’s disease (AD). PMN310 is a humanized IgG1 monoclonal antibody that binds to a computationally derived three‐dimensional epitope specific to misfolded Aβ in AβO. Because PMN310 inhibits toxicity of AβO and does not bind to plaque, thereby potentially limiting risk of ARIA, it is being developed as a therapy for early AD. Results from a single ascending dose study of PMN310 (A Phase 1a Study of PMN310 In Healthy Volunteers NCT06105528) indicate that PK parameters and CSF concentrations of PMN310 were linearly dose‐dependent and CSF concentrations were 100‐600 times the estimated AβO molar concentration. The plasma half‐life (t ½) was approximately 17.5 days and the CSF t ½ was approximately 27 days.

Methods:

PRECISE‐AD, NCT06750432, is a placebo‐controlled, multiple‐ascending dose study of PMN310 to evaluate safety, tolerability, PK, PD, and preliminary efficacy of multiple intravenous infusions of PMN310 in patients with early Alzheimer's disease. The study consists of three staggered dosing arms of 350 mg, 700 mg, 1400 mg. Patients will be randomized 3:1, PMN310: placebo and will receive either PMN310 or placebo once every 28 days for a total of 12 infusions. The study will enroll 128 patients with either Stage 3 or 4 AD. Diagnosis will be determined by clinical criteria, CSF and plasma biomarkers, and Aβ PET. MRI scans will be done at months 2, 4, 6, 9, 12 to detect potential ARIA. Plasma biomarkers (pTau217, pTau 243, GFAP, SNAP25, neurogranin, Aβ42/Aβ40, NfL) will be measured at baseline and at 3‐month intervals. Biomarkers in CSF will be measured at baseline, 6, 12 months. Cognitive outcomes (CDR‐SB, ADAS‐cog, ADAS‐ADL IADRS Clinical Impression of Change) will be assessed at baseline, month 6 and month 12.

Results:

The proposed study has sufficient power to detect at least one ARIA event. The proposed sample size has sufficient power to provide statistically meaningful insight into effects of PMN310 on biomarkers and clinical outcomes.

Conclusions:

PRECISE‐AD will be the first study to examine the effects of a monoclonal antibody directed solely against AβO on biomarkers associated with AD pathology and clinical outcomes.

2025-12-01·Alzheimers & Dementia

Protein misfolding‐specific epitope identification for passive and active immunotherapy of neurodegenerative diseases

Review

作者: Coutts, Juliane ; Gibbs, Ebrima ; Plotkin, Steven S ; Kaplan, Johanne ; Scruten, Erin ; Zhao, Beibei ; Cashman, Neil R ; Napper, Scott

Abstract:

Background:

Toxic misfolded proteins underlie the pathogenesis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (AD&PD), and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Generation of therapeutic antibodies selectively targeting only disease‐misfolded isoforms, while sparing normal or irrelevant isoforms, has not yet been successfully achieved by conventional immunization strategies.

Method:

ProMIS Neurosciences has developed a computational platform to identify conformational epitopes that are uniquely exposed on toxic misfolded proteins, which can then be used to generate misfolding‐specific antibodies or vaccine formulations.

Result:

Application of the ProMIS platform produced PMN310, a clinical‐stage, humanized monoclonal antibody highly selective for Abeta oligomers without significant reactivity with Abeta monomers or fibrils, thereby avoiding target distraction by these more abundant species, and reducing the risk of brain edema and microhemorrhages associated with the targeting of vascular/parenchymal amyloid. Similarly, specific epitopes for alpha‐synuclein toxic oligomers/soluble fibrils that drive synucleinopathies, and for pathogenic TDP‐43 in ALS/FTD have been identified and lead candidate antibodies generated. The small size and precise conformation of these epitopes have been translated into vaccines, enabling the specific targeting of pathogenic molecular species in preclinical models.

Conclusion:

ProMIS has circumvented the specificity limitations of conventional immunizations to enable selective passive and active immunotherapies for neurodegenerative diseases.

2025-10-01·Alzheimers & Dementia-Translational Research & Clinical Interventions

Relationship between efficacy and preferential targeting of soluble Aβ aggregates

Article

作者: Johanne M. Kaplan ; Neil R. Cashman ; Juliane A. Coutts ; Beibei Zhao ; Ebrima Gibbs ; Ian R. Mackenzie ; Steven S. Plotkin

Abstract:

INTRODUCTION:

Amyloid beta (Aβ)‐directed antibodies have shown varying degrees of efficacy against Alzheimer's disease (AD). This study explored the relationship between targeting of Aβ molecular species and therapeutic efficacy/adverse effects.

METHODS:

Surface plasmon resonance was used to measure binding of various Aβ‐directed antibodies to monomers and soluble oligomers from AD brains. Plaque reactivity was assessed by immunohistochemistry and immunofluorescence. Antibody PMN310 was tested in AD mouse models.

RESULTS:

Pan‐Aβ reactive antibodies that failed in the clinic lost the ability to bind AD brain oligomers when competing with monomers. Lecanemab, aducanumab, and donanemab, which slowed cognitive decline, and early stage PMN310 and ACU193 showed a greater ability to withstand monomer competition. All antibodies bound plaque except for PMN310. In mouse models, PMN310 protected cognition and was not associated with microhemorrhages.

DISCUSSION:

These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid‐related imaging abnormalities (ARIA).

Highlights:

Selectivity for toxic Aβ oligomers has potential to maximize efficacy and safety.Avoidance of Aβ monomers increases binding to toxic AD brain oligomers.Avoidance of Aβ plaque/vascular deposits reduces the risk of ARIA.

103

项与 PMN-310 相关的新闻（医药）

2026-07-30

·思索新知

阿尔茨海默病新药PMN310早期试验结果积极，ARIA风险或降低

阿尔茨海默病治疗领域近几年最热门的发展方向之一，就是清除大脑中的淀粉样蛋白。随着多款抗淀粉样蛋白抗体陆续获批，人们开始看到延缓疾病进展的可能性，但与此同时，一种名为ARIA的副作用也成为限制这类药物广泛应用的重要因素。如何在保持治疗效果的同时降低ARIA风险，已经成为新一代阿尔茨海默病药物研发的核心目标。近日，ProMIS Neurosciences公布了PMN310在阿尔茨海默病Ⅰb期临床试验中的一项中期结果。研究进行至6个月时，研究人员未观察到ARIA相关影像学异常信号。这一结果虽然仍属于早期安全性数据，但对于抗淀粉样蛋白治疗领域来说，无疑是一个值得关注的积极进展。真正受到关注的是没有出现ARIA ARIA全称为淀粉样蛋白相关影像学异常，是目前抗淀粉样蛋白抗体治疗中最令人关注的不良反应之一，主要包括脑水肿和脑微出血。由于存在这一风险，接受治疗的患者通常需要定期进行MRI检查，以便及时发现异常情况，也增加了治疗成本和临床管理难度。 PMN310正是围绕这一问题进行设计的一款新型单克隆抗体。它属于人源化IgG1单克隆抗体，但与目前已经上市或进入临床的同类药物不同，它并不是广泛结合所有淀粉样蛋白，而是选择性识别具有毒性的淀粉样蛋白β寡聚体。研究人员认为，这类毒性寡聚体被认为是导致神经元损伤的重要因素，而形成斑块的大型纤维样淀粉样蛋白往往沉积在脑血管周围，与ARIA的发生存在一定关联。因此，PMN310希望通过更加精准的靶向策略，在保留治疗作用的同时，减少对脑血管相关淀粉样蛋白的影响，从源头降低ARIA发生风险。此次公布的是PRECISE-AD随机、双盲、安慰剂对照、多剂量递增Ⅰb期研究的6个月盲态中期分析结果。公司介绍，研究在安全性和生物标志物方面均获得积极数据，目前独立数据安全监察委员会（DSMB）也未发现需要暂停或终止试验的安全问题，因此研究将继续按计划推进。不过，由于目前仍属于盲态分析阶段，所有疗效数据尚未正式公布，因此现阶段还无法判断PMN310是否能够真正改善患者认知功能，最终结论仍需等待后续完整数据公开。近年来，阿尔茨海默病治疗格局正在快速变化。2024年，多奈单抗获得美国FDA批准，加上此前获批的Lecanemab和Aducanumab，抗淀粉样蛋白治疗已经逐渐进入临床实践。与此同时，这类药物带来的ARIA风险也让临床医生积累了越来越多管理经验，包括MRI监测、剂量调整以及根据APOE基因型进行风险评估等措施，都已成为临床治疗的重要组成部分。如果PMN310未来能够持续证明自身几乎不会诱发ARIA，那么整个抗淀粉样蛋白治疗策略都有可能发生新的变化。医生或许能够减少MRI监测频率，提高给药灵活性，同时降低患者因安全风险带来的心理压力和治疗负担，尤其对于ARIA风险较高的APOE4携带者来说，意义可能更加明显。当然，目前真正决定PMN310未来价值的，仍然不是没有出现ARIA，而是在保证安全性的同时，是否能够有效结合毒性淀粉样蛋白寡聚体，并最终转化为临床疗效。未来公布的生物标志物数据，包括血浆p-tau217变化以及淀粉样蛋白PET影像结果，将进一步回答这一关键问题。如果这些指标能够证实PMN310确实影响了疾病相关病理过程，同时维持目前观察到的良好安全性，这款药物将有望进入Ⅱ期临床研究，并为阿尔茨海默病患者提供一种更加安全的新一代抗淀粉样蛋白治疗选择。 🔹本文供医学科普使用，不构成医疗建议。本文内容基于公开资料整理，包括但不限于Fierce Biotech、The Guardian、Reuters、Nature、STAT News 等权威媒体与期刊。所有翻译与解读仅用于知识分享与医学科普，不构成任何医疗建议或临床指导。 🔹本文由「思索新知」团队基于海外权威资料整理，致力于提供可信赖的全球医疗科技动态。

2026-07-29

·Pharmaindustrial

ProMIS Neurosciences Reports Positive Interim Phase 1b Results for Alzheimer's Therapy PMN310

ProMIS Neurosciences has announced positive blinded six-month interim safety and biomarker results from its ongoing PRECISE-AD Phase 1b clinical trial evaluating PMN310 in patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease. The interim analysis included 136 patients and demonstrated a favourable safety profile across all genotypes. No cases of Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) were reported as of the data cutoff date, while the overall incidence of ARIA was 4.4 percent, consisting entirely of mild, asymptomatic ARIA-H cases. The study also reported no treatment-related serious adverse events or drug-related discontinuations. The favourable safety profile was observed even among patients carrying the APOE4 genotype, a group considered at higher risk and often underserved by currently approved amyloid-targeting therapies. The study population included 61 percent APOE4 carriers, of whom 11 percent were homozygotes. Blinded interim biomarker analyses also indicated early, directionally consistent reductions in disease-related biomarkers. Approximately 68.5 percent of patients showed declines in plasma pTau217, while 62.5 percent recorded reductions in CSF MTBR-tau243, compared with expected increases based on the natural progression of the disease. The company noted that these observations remain blinded and are not a confirmation of clinical efficacy. PMN310 is designed to selectively target toxic amyloid-beta oligomers while avoiding amyloid plaques, a differentiated mechanism intended to reduce the risk of ARIA commonly associated with existing plaque-binding therapies. The PRECISE-AD study is a randomised, double-blind, placebo-controlled Phase 1b trial evaluating the safety, tolerability and pharmacokinetics of multiple ascending intravenous doses of PMN310 in patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease. The study has completed enrollment of 144 participants across three dosing cohorts, with patients receiving treatment for 12 months. Unblinded topline results, including efficacy data, are expected in the first quarter of 2027. PMN310 received Fast Track Designation from the US Food and Drug Administration (FDA) in July 2025. The therapy follows encouraging results from an earlier Phase 1a study conducted in healthy volunteers and is being developed as a potential treatment for Alzheimer's disease with an improved safety profile.

临床结果快速通道临床1期临床2期

2026-07-28

·药明康德

治疗酒精使用障碍，GLP-1药物达到2期临床试验主要终点；HIV复方疗法达到3期临床主要终点…… | 产业新闻

治疗酒精使用障碍，胰高血糖素/GLP-1双受体激动剂达到2期临床试验主要终点 Altimmune今日宣布，在中度至重度酒精使用障碍（AUD）患者中评估在研胰高血糖素/胰高血糖素样肽-1（GLP-1）双受体激动剂pemvidutide的2期临床试验RECLAIM取得积极顶线结果。该试验达到主要终点：与安慰剂相比，pemvidutide可减少重度饮酒天数（HDD），差异具有高度统计学显著性。基于该试验结果，公司计划向美国FDA申请召开2期临床试验结束会议。主要疗效结果为与安慰剂相比，每周重度饮酒天数这一主要终点显著减少（p=0.0014）。多项次要终点结果具有统计学显著性：与安慰剂相比，世界卫生组织（WHO）饮酒风险水平降低两个等级（p=0.0049）；与安慰剂相比，实现重度饮酒天数为零（p=0.0066）；与安慰剂相比，未饮酒天数比例的变化具有统计学显著性（p=0.0075）；与安慰剂相比，磷脂酰乙醇（PEth）水平显著降低（p<0.0001）；体重显著降低，第24周时，体重较基线的降幅经安慰剂校正后为9.1%（p<0.0001），且未观察到减重平台期。 Pemvidutide是一款新型在研多肽，具有平衡的胰高血糖素/GLP-1双受体激动活性，目前正在开发用于治疗代谢功能障碍相关性脂肪性肝炎（MASH）、酒精使用障碍和酒精相关性肝病（ALD）。激活胰高血糖素受体可直接作用于肝脏，包括减少肝脏脂肪、炎症和纤维化；GLP-1受体则介导食欲抑制和体重减轻等代谢效应，并可能参与与渴求和奖赏相关的通路。FDA已授予pemvidutide用于治疗MASH和AUD的快速通道资格，并授予其用于治疗MASH的突破性疗法认定。阿尔茨海默病新型疗法早期临床结果积极 ProMIS Neurosciences今日宣布，其主要候选药物PMN310用于治疗阿尔茨海默病（AD）所致轻度认知障碍或轻度阿尔茨海默病患者的1b期PRECISE-AD试验取得积极的盲态6个月中期安全性和生物标志物结果。在对136例AD患者开展的盲态中期分析中，PMN310在所有基因型患者中均表现出良好的安全性特征。截至数据截止日期，未报告淀粉样蛋白相关影像异常伴水肿（ARIA-E）病例；与此同时，与疾病相关的生物标志物出现了早期、方向一致的变化，这些变化可能反映了试验的随机分组模式。目前，该试验仍处于盲态并持续进行中，预计将于2027年第一季度公布12个月顶线结果。中期结果亮点：所有基因型患者均表现出良好的安全性特征：未发生ARIA-E，总体ARIA发生率为4.4%，均为轻度且无症状。截至中期分析时，未发生与治疗相关的严重不良事件，也未出现因药物相关原因导致的停药。高风险APOE4携带者中的安全性特征一致：在受试者中，APOE4携带者占61%，其中11%为APOE4纯合子；所有基因型患者均未观察到ARIA-E。早期生物标志物变化与药物作用于预期靶点相一致：在盲态分析中，大多数患者的疾病相关生物标志物水平下降，而按照自然病程轨迹，这些指标原本预计会升高。68.5%的患者血浆pTau217较基线下降，62.5%的患者脑脊液MTBR-tau243水平下降。这些结果与潜在的有益药物效应一致，也可能反映该试验活性药物组与安慰剂组按3：1比例随机分组的设计。上述结果为盲态中期生物标志物观察结果，即目前尚不清楚患者被分配至药物组还是安慰剂组。这些生物标志物趋势并不能用于判定疗效，其最终也未必能够反映临床效果。 PMN310是ProMIS用于治疗AD的主要候选产品，是一种人源化IgG1单克隆抗体，旨在选择性靶向有毒的淀粉样蛋白β寡聚体。此类寡聚体被认为是阿尔茨海默病最早出现且破坏性最强的驱动因素之一。PMN310可避免与淀粉样蛋白斑块和血管沉积物结合。这种选择性可能降低或消除ARIA的风险，ARIA通常与结合淀粉样蛋白斑块的抗体有关。2025年7月，美国FDA授予PMN310快速通道资格。 ViiV Healthcare复方HIV疗法3b期临床试验结果积极 ViiV Healthcare宣布，将于本周在巴西里约热内卢举行的第26届国际艾滋病大会（AIDS 2026）上公布3b期VOGUE研究数据。数据显示，在初治HIV-1感染成人中，Dovato（多替拉韦/拉米夫定）的疗效与活性对照组相比，达到非劣效性标准。正在开展的VOGUE研究是一项多国、多中心、开放标签3b期临床试验，共随机纳入509例初治HIV-1感染成人患者，分别接受Dovato（n=254）或Biktarvy（n=255）治疗。基线时，47%的受试者病毒载量≥100,000拷贝/mL，16%的受试者病毒载量≥500,000拷贝/mL，16%的受试者CD4+细胞计数<200个/mm³。第48周时，Dovato组有89%的受试者实现病毒学抑制（HIV-1 RNA<50拷贝/mL；n=226/254），活性对照组的比例为92%（n=235/255），校正后差异为-3%，95% CI为-8%～2%，达到研究预设的非劣效性终点。两组实现病毒学抑制的中位时间均较短且相近，均为4.1周。两个治疗组均未发现治疗期间出现的耐药。两组的总体安全性特征相当，未观察到新的安全性信号。两组因未能实现或维持病毒学抑制而停止治疗的受试者人数相同，均为7例。参考资料： [1] Altimmune Announces Positive Topline Results from RECLAIM Phase 2 Trial of Pemvidutide in Alcohol Use Disorder. Retrieved July 28, 2026, from https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-positive-topline-results-reclaim-phase-2 [2] ProMIS Neurosciences Reports Positive Blinded Six-Month Interim Safety and Biomarker Data for PMN310 in the PRECISE-AD Phase 1b Alzheimer’s Disease Trial. Retrieved July 28, 2026, from https://www.globenewswire.com/news-release/2026/07/28/3334059/0/en/promis-neurosciences-reports-positive-blinded-six-month-interim-safety-and-biomarker-data-for-pmn310-in-the-precise-ad-phase-1b-alzheimer-s-disease-trial.html [3] ViiV Healthcare’s 2-drug regimen Dovato is as effective as 3-drug regimen Biktarvy in first-of-its-kind head-to-head study in treatment-naïve adults living with HIV. Retrieved July 28, 2026, from https://www.businesswire.com/news/home/20260727256393/en/ViiV-Healthcares-2-drug-regimen-Dovato-is-as-effective-as-3-drug-regimen-Biktarvy-in-first-of-its-kind-head-to-head-study-in-treatment-nave-adults-living-with-HIV 免责声明：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：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……

100 项与 PMN-310 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
阿尔茨海默症	临床1期	-	ProMIS Neurosciences, Inc.	2023-11-20

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


NCT06105528 (GlobeNewswire) 人工标引	临床1期	阿尔茨海默症	40	PMN310	簾鏇構製壓窪窪顧願觸(簾構齋糧壓範鬱襯構積) = None 遞鹹蓋鹽齋獵鹽鬱顧窪 (醖積遞觸夢構願鹹夢廠 ) 更多	积极	2024-07-26
				Placebo