Phase 2 Clinical Platform Trial Investigating Multiple Therapeutic Options for the Treatment of Hospitalized Patients With Acute Respiratory Distress Syndrome (ARDS)

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design.
Cohort B: Participants will be randomized to receive either a placebo or paridiprubart.
This record describes the default procedures and analyses for Cohort B. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

开始日期2025-06-10

申办/合作机构

PPD Development LP

[+4]

NCT06703073

/ Recruiting临床2期

Phase 2 Clinical Platform Trial Investigating Multiple Therapeutic Options for the Treatment of Hospitalized Patients With Acute Respiratory Distress Syndrome (ARDS)

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Participants will be randomized to receive either a placebo or one of the active treatments.
This record describes the default procedures and analyses for all cohorts. Each specific cohort may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in the corresponding intervention-specific records on clinicaltrials.gov listed below in the detailed description.

开始日期2025-06-10

申办/合作机构

PPD Development LP

[+4]

NCT04401475

/ Suspended临床2/3期

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of EB05 + SOC Vs. Placebo + SOC in Adult Hospitalized Patients with COVID-19

COVID-19 patients who develop severe disease often develop acute respiratory distress syndrome (ARDS) as a result of a dysregulated immune response. This in turn stimulates a pro-inflammatory cascade ("cytokine storm") as well as emergency myelopoiesis.
This proinflammatory cascade is activated when viral-mediated cell damage occurs in the lungs, resulting in the release of damage-signaling alarmin molecules such as S100A8/A9 (Calprotectin), HMGB1, Resistin, and oxidized phospholipids. These damage-associated molecular patterns (DAMPs) are recognized by the pattern recognition receptor Toll-Like Receptor 4 (TLR4) found on macrophages, dendritic cells and other innate immune cells and result in additional release of pro-inflammatory molecules. Several recent studies have shown that S100A8/A9 serum levels in hospitalized COVID-19 patients positively correlate with both neutrophil count and disease severity. Taken together the DAMP-TLR4 interaction forms a central axis in the innate immune system and is a key driver of the pathological inflammation observed in COVID-19. We hypothesis that targeting the initial step in the signalling pathways of these DAMPs in innate immunity offers the best hope for controlling the exaggerated host response to SARS-CoV-2 infection.
EB05 has demonstrated safety in two clinical studies (>120 patients) and was able to block LPS-induced (TLR4 agonist) IL-6 release in humans. Given, this extensive body of evidence we believe EB05 could ameliorate ARDS due to COVID-19, significantly reducing ventilation rates and mortality.

开始日期2020-11-25

申办/合作机构

Edesa Biotech, Inc.

[+1]

100 项与 NI-0101 相关的临床结果

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100 项与 NI-0101 相关的转化医学

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100 项与 NI-0101 相关的专利（医药）

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项与 NI-0101 相关的文献（医药）

2024-07-01·Pharmaceutical Medicine

Statistical Signal Detection Algorithm in Safety Data: A Proprietary Method Compared to Industry Standard Methods

Article

作者: Allen, Jeff K ; Philip, Jeff ; Bastos, Eugenia

INTRODUCTION:

Several quantitative methods have been established, in pharmacovigilance, to detect signals of disproportionate reporting (SDRs) from databases containing reports of adverse drug reactions (ADRs). The signal detection algorithms (SDAs) and the source of the reporting per product vary, but it is unclear whether any algorithm can provide satisfactory performance using data with such large variance factors.

OBJECTIVE:

Determine the appropriate SDA for Biogen's internal Global Safety Database (GSD) given the characteristics of the database including frequencies of events, data skewness, outliers, and missing information. Compare performance of standard approaches (EBGM, EB05, PRR, and ROR), well accepted by industry, to a Biogen-developed Machine Learning (ML) Regression Decision Tree (RDT) model, across several Biogen products, to determine a champion SDA.

METHODS:

All data associated with seven marketed Biogen products were chosen and a historical subset of reported ADRs were considered. Six SDAs (five common industry disproportionality methods) and RDT were evaluated. The SDRs were calculated on training and test data composed of quarterly reporting intervals from 2004-2019. The performance measures used were sensitivity, precision, time to detect new events, and frequency of detected cases for each algorithm for each product. Outcomes in the test data are known a priori and easily compared to predicted outcomes. Validation was performed via rates of misclassification. This work solely represents Biogen's internal information, intentionally chosen to serve the performance review of its signal detection systems, and results will not necessarily be generalizable to other external sources.

RESULTS:

Several algorithms performed differently among products, but no one method dominated any other. Performance was dependent on the thresholds used to define a signal according to different criteria. However, those different statistics subtly influenced the achievable performance. The relative performance of RDT and Medicines and Healthcare products Regulatory Agency (MHRA) algorithms were superior and paired across products. A reduction in precision for all methods spanning the products was present. Hence, companies evaluating signal detection approaches, search for innovative methods to minimize this effect.

CONCLUSIONS:

In designing signal detection systems, careful consideration should be given to the criteria that are used to define SDRs. The choice of disproportionality statistics does not affect the achievable range of signal detection performance. These choices should consider mainly ease of implementation and interpretation. The implementation of a method is specific to its accuracy. The RDT attempted to take advantage of known methods and compare results on a per-product basis. Many factors influencing ADRs may improve RDT in future efforts. In this experiment, RDT demonstrated superiority in terms of quickest time to detect and capturing of the highest number of ADRs. Next steps include expansion of data for products representing other indications and testing models in external databases to investigate generalizability of estimates when comparing SDAs.

2020-03-01·Annals of the rheumatic diseases1区 · 医学

Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patients with rheumatoid arthritis after inadequate response to methotrexate: a phase II study

1区 · 医学

Article

作者: Choy, Ernest H ; Jacqmin, Philippe ; McInnes, Iain ; Lapeyre, Geneviève ; de Min, Cristina ; Kobakhidze, Tamta ; de Graaf, Kathy ; Monnet, Emmanuel

Objectives:

Anti-citrullinated protein antibodies (ACPAs) form immune complexes with citrullinated proteins binding toll-like receptor (TLR) 4, which has been proposed as a mediator of rheumatoid arthritis (RA). NI-0101 is a first-in-class humanised monoclonal antibody blocking TLR4, as confirmed by inhibition of in vivo lipopolysaccharide-induced cytokine release in healthy volunteers. This study was design to confirm preclinical investigations supporting a biomarker-driven approach for treatment of patients with RA who present positive for these immune complexes.

Methods:

Placebo-controlled, double-blind, randomised (2:1) trial of the tolerability and efficacy of NI-0101 (5 mg/kg, every 2 weeks for 12 weeks) versus placebo in ACPA-positive RA patients with inadequate response to methotrexate. Efficacy measures included Disease Activity Score (28-joint count) with C reactive protein (DAS28-CRP), European League Against Rheumatism (EULAR) good and moderate responses, and American College of Rheumatology (ACR) 20, ACR50 and ACR70 responses. Subgroup analyses defined on biomarkers were conducted. Pharmacokinetics, pharmacodynamics and safety were reported.

Results:

90 patients were randomised (NI-0101 (61) and placebo (29)); 86 completed the study. No significant between-group difference was observed for any of the efficacy endpoints. Subgroup analyses using baseline parameters as covariants did not reveal any population responding to NI-0101. Treatment-emergent adverse events occurred in 51.7% of patients who received placebo versus 52.5% for NI-0101.

Conclusions:

We demonstrate for the first time that in RA, a human immune-mediated inflammatory disease, blocking the TLR4 pathway alone does not improve disease parameters. Successful targeting of innate immune pathways in RA may require broader and/or earlier inhibitory approaches.

2017-11-01·Pharmacotherapy

Pharmacovigilance Assessment of Immune‐Mediated Reactions Reported for Checkpoint Inhibitor Cancer Immunotherapies

Article

作者: Watson, David E. ; Ali, Ayad K.

Study Objective:

Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors ( CPIs ) that activate T‐cell–mediated immune response. CPI can provide durable benefits to some cancer patients with melanoma, renal cell cancer, non–small cell lung cancer, or a growing list of other cancers. However, CPI treatment is also associated with adverse immune‐mediated reactions ( IMRs ) that can be life‐threatening. This pharmacovigilance analysis aims to characterize IMR signals in relation to CPI treatment.

Design:

Retrospective pharmacovigilance disproportionality analysis.

Data Source:

U.S. Food and Drug Administration Adverse Event Reporting System ( FAERS ).

Measurements and Main Results:

Adverse event reports submitted to FAERS between 2011 and 2015 were analyzed. CPIs were identified by generic names, and IMRs were identified by Med DRA Preferred Terms. Empirical Bayes geometric means with corresponding 95% confidence intervals ( EB 05‐ EB 95) were calculated as CPI ‐ IMR association metrics. Signals were defined as metrics with EB 05 ≥ 2.0. Overall, 1,018 IMR events were submitted for CPIs , corresponding to 76% for ipilimumab, 15% for nivolumab, and 9% for pembrolizumab. The period of data collection precluded data on the most recently approved CPI agents. IMRs consisted of 51% colitis, 16% endocrinopathies, 12% pneumonitis, 11% hepatitis, 4% infusion‐related reactions, 3% nephritis, and 3% other IMRs . Colitis contributed to 63% and 41% of IMRs for ipilimumab and nivolumab, respectively. Pneumonitis and hepatitis contributed to a majority of IMRs for pembrolizumab, for which nephritis and infusion‐related reactions were not reported. Signals of IMRs were detected for CPIs as a class ( EB 05 = 12.4) and individual agents: ipilimumab ( EB 05 = 13.2), nivolumab ( EB 05 = 15.0), and pembrolizumab ( EB 05 = 7.3). Colitis and pneumonitis had the strongest signals for CPIs ( EB 05 = 45.6 and EB 05 = 17.6, respectively). Colitis was the strongest signal for ipilimumab ( EB 05 = 54.2), and pneumonitis was the strongest signal for nivolumab ( EB 05 = 48.0) and pembrolizumab ( EB 05 = 21.8).

Conclusion:

Cancer immunotherapy with CPIs is associated with a multitude of IMRs , especially colitis and pneumonitis. Individual CPIs had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals.

项与 NI-0101 相关的新闻（医药）

2025-11-03

·大药时记

FDA一周回顾：FDA降低生物仿制药上市门槛等

美国卫生与公共服务部（HHS）近日批准包括默沙东、BMS等在内的八家制药企业，参与一项创新的340B药品折扣返利试点项目。340B Rebate Model Pilot Program（340B返利模式试点项目）于2025年7月底宣布推出。这是一个自愿性试点，旨在测试从传统的预付折扣（up-front discounts）模式向售后返利（post-sale rebates）模式的转变。该项目最初仅适用于CMS（医疗保险和医疗补助服务中心）Medicare药物价格谈判选定药物列表上的特定药品。试点旨在评估这种模式的优缺点，并解决合规问题，如重复折扣（duplicate discounts）和药品转移（diversion）。新试点转向售后返利（post-sale rebates）是合格实体先以全价（WAC）通过批发商账户购买药品，随后，在药品分发给合格患者后45天内提交索赔级数据（claim-level data，包括服务日期、处方号、NDC代码、数量等）。制造商在收到数据后10天内支付单位级返利，以实现等同于天花板价格的净效果。制造商需承担所有IT和行政成本，提供至少60天通知和技术支持，并通过HRSA批准的平台处理。双方需维护可审计记录，HRSA将进行审计以确保合规。 Kyverna的CD19靶向CAR-T免疫疗法KYV-101在全身性重症肌无力（gMG）临床2期试验中达到了100%的缓解率。此次公布的中期数据来自KYSA-6研究，该研究为一项单臂、开放标签的注册性临床试验，旨在评估KYV-101对患者日常生活能力的改善情况。截止目前，六名中重度全身性重症肌无力（gMG）患者已完成评估，且此前未对免疫抑制剂产生反应。根据Kyverna的说明，经过36周治疗，这六名患者的日常生活能力均实现了临床意义上的改善，相较于基线水平明显提升。所有患者都达到了疗效反应标准，定义为在两个疾病评分指标中至少减少3分。中期数据显示，KYV-101或能减轻患者的治疗负担。所有患者在24周后都可停止使用非甾体免疫抑制剂、高剂量激素及其他辅助药物。安全性方面，Kyverna报告称KYV-101耐受性良好，未出现高等级的细胞因子释放综合征（CRS）或免疫效应细胞相关神经毒性（ICANS）病例。不过有一名患者出现了4级（生命威胁性）中性粒细胞减少症。Kyverna认为这一不良反应是预期之中的，且该患者在数据截止时已改善至1级。公司计划将KYSA-6的三期临床试验纳入后续阶段，预计今年底开始患者招募。 Regenron计划在美国建立或扩建多个生产基地，以满足其创新药物和生物制剂的生产需求。 Tectonic Therapeutic公布了其长效Fc-relaxin融合蛋白TX45在HFrEF（射血分数减低型心力衰竭）伴肺动脉高压（PH-HFrEF）患者中的第二组1b临床试验的初步积极结果。数据显示，单次静脉注射TX45在该患者群体中具有良好的耐受性，并显著改善了左心功能和肺血流动力学指标。该试验特别关注联合前后毛细血管性肺动脉高压（CpcPH）且肺血管阻力（PVR）超过3 WU的患者，主要终点设在这一亚组。该开放标签的阶段b试验共纳入14名PH‑HFrEF患者，具体包括：7名符合CpcPH（PVR>3 WU）标准的患者，5名PVR>2 WU且<3 WU的患者，以及2名单纯的后毛细血管性肺动脉高压（IpcPH，PVR<2 WU）患者。血流动力学监测结果显示，TX45的给药在改善左心功能和肺血管状态方面均取得了显著成效，尤其是在严重病理状态的CpcPH患者中。肺毛细血管楔压（PCWP）平均下降29.2%，表明左心压力得到有效缓解；PVR（肺血管阻力）在PVR>3 WU的患者中下降了19.7%，在PVR>2 WU且<3 WU的患者中下降了10.3%，显示出明显的血管扩张作用；其他血流动力学指标如心排血量（CO）、总肺血阻力（TPR）和平均肺动脉压（mPAP）也呈现出改善趋势。 BridgeBio宣布其在治疗遗传性甲状腺疾病方面的最新临床数据表现优异，推动股价再上涨近8%。接受encaleret治疗的患者中，有76%在第24周达到了目标血钙水平，而对照组的患者仅有4%。这一结果远超市场预期，也优于第二期临床数据显示的69%的血钙控制率。结果显示，药物不仅达到了预期的血钙调节目标，还降低了尿钙排泄。在关键次要指标方面，有91%的患者在第24周实现了完整的内源性甲状腺激素（PTH）水平控制。Encaleret 是一种研究性药物，用于治疗常染色体显性低钙血症 1 型 (ADH1) 等疾病，其作用机制是作为钙敏感受体 (CaSR) 的选择性拮抗剂。 FDA正式拒绝Regeneron的高剂量Eylea预充填注射器的审批请求。主要原因是负责生产的第三方工厂存在合规问题，包括持续未解决的污染和预防措施不足。早在第二季度财报中Regeneron曾暗示其Eylea HD申请遇到问题，指出在由诺和诺德运营的某生产基地观察到异常情况。随后，公司披露FDA将这些审批决定推迟至第四季度。近日，诺和诺德通知Regeneron，该工厂已被FDA归类为“正式行动指示（Official Action Indicated）”，显示该工厂存在“不可接受的合规状态”，包括持续的污染和预防措施不足等问题。 Aldeyra宣布放弃RASP调节剂ADX-629的研发。该药曾被研究用于多种免疫介导疾病，包括哮喘、慢性咳嗽和特应性皮炎。然而，尽管在一项II期酒精相关肝炎研究中，ADX-629显示出改善肝功能和炎症指标的统计学意义，但公司决定终止其研发。公司同时公布了相关临床数据，显示药物在改善肝功能方面具有一定效果，且安全性良好，未出现严重不良反应。公司未明确说明终止ADX-629的具体原因，但资金压力可能是重要因素之一。与此同时，Aldeyra还宣布将推进两款新一代RASP调节剂，以替代现有的老一代分子。比如，在涉及肥胖和高甘油三酯血症的代谢性炎症领域，公司将重点开发ADX-248。在一项I期临床试验中，ADX-248表现出良好的药代动力学特性，药物在体内的暴露水平高，且每日口服剂量安全有效。这款新药将取代另一款候选药物ADX-743。默沙东的口服小分子HIF-2α抑制剂Welireg在两项针对早期肾癌患者的III期临床试验中取得主要终点。试验中，将Welireg作为辅助治疗加入Keytruda（帕博利单抗），手术切除后显著延长了患者的无疾病生存期（DFS），优于单独使用Keytruda。在另一项试验中，Welireg与卫材（Eisai）旗下的Lenvima（仑伐替尼）联合治疗复发患者，也优于Cabometyx（卡博替尼），在延缓疾病进展方面表现更佳。Welireg的建议零售价为每月3万美元，治疗周期54周。 FDA正式宣布暂停Intellia Therapeutics的两项III期临床试验，MAGNITUDE和MAGNITUDE-2研究。这两项试验正在评估由CRISPR基因编辑技术修饰的基因疗法nexiguran ziclumeran（nex-z）在治疗转甲状腺素淀粉样变（ATTR）伴心肌病（ATTR-CM）和多发性神经病（ATTR-PN）中的安全性和有效性。虽然FDA目前仅以口头通知暂停决定，但预计将在未来30天内发出正式书面通知。公司首次披露安全信号时称一名MAGNITUDE试验受试者出现转氨酶和胆红素水平升高，达到4级（即生命威胁级别），并于9月30日记录在案，患者随后住院接受治疗。在此之前，2022年8月，Intellia在一项早期临床试验中也曾报告过类似的肝酶升高事件，虽为无症状且在28天内自行缓解，但显示出nex-z在安全性方面存在一定风险。去年5月，公司还曾披露另一名患者出现4级肝酶升高反应，但当时未暂停试验，届时分析师对此普遍持较为轻松的态度。 FDA公布了一份关于生物仿制药的新草案指南。HHS表示，这一政策有望让仿制生物药在无需进行繁琐的人体试验的情况下上市，从而借助市场力量降低药品价格。FDA正考虑简化仿制药的审批流程，旨在推动药价下降，减少行政壁垒。官方指出，免除高昂的临床试验将有助于加快仿制药的研发和上市速度，为患者提供比品牌药更经济的治疗选择。新指南提出多项变革措施，旨在“简化生物相似性研究”，为那些与已获批准的参考药品高度相似、可互换的仿制药提供“更便捷的许可途径”。按照新框架，企业可能无需每次都进行大规模、高成本的人体试验，只要仿制药的效果和安全性与原研药相当。虽然申请仿制药上市的企业仍需证明其产品具备与原药的互换性，但在新指南中，FDA将决定是否需要进行比较疗效研究（CES），即比较两药在临床中的实际疗效。也可能认定，只需依靠临床前和生化数据的“比较分析”即可。指南建议，在仿制药与参考药品由克隆细胞生产、纯度高且可以通过临床前检测直接比对的情况下，可以采用更“简洁”的审批流程。不过FDA也明确表示，在某些特殊情况下，仍需进行人体试验，比如局部用药（如眼药）或以非临床终点评估疗效的药物。诺华发布的NEPTUNUS-1和NEPTUNUS-2两项III期临床试验数据显示，其全人源抗 BAFF-R 单克隆抗体ianalumab在干燥综合征患者中表现出显著的疗效，成功降低了疾病的活跃程度和患者的生活负担。干燥综合征是第二常见的风湿性自身免疫疾病，目前尚无专门的靶向治疗药物。Ianalumab具有双重作用机制：既能耗竭B细胞，又能靶向BAFF受体。这一假设得到了临床数据的验证。数据显示，到第16周时，ianalumab相较于安慰剂，显著改善了疾病活跃度，且这一效果持续至第52周，达到了欧洲风湿病联盟（EULAR）制定的疾病活动指数（ESSDAI）主要终点指标。同时，患者在干燥、疼痛和疲劳等主要症状方面也持续获益。 FDA正式批准了拜耳研发的全新非激素性药物Lynkuet，用于治疗绝经后女性的中重度热潮红。该药基于三项大规模临床试验，成功证明其能显著减少热潮红的频率和严重程度，改善患者的生活质量。血管运动症状主要在绝经期及其后出现，表现为热潮红、夜汗等不适。这些症状由雌激素水平下降引发，持续时间不一，严重影响女性的日常生活和工作效率。虽然激素替代疗法（HRT）曾是主流治疗手段，但并非所有女性都适用，部分人因潜在健康风险选择放弃。市场上另一款非激素药物Veozah由安斯泰来制药于2023年推出，但由于市场需求未达预期，加之出现肝损伤的安全警示，其商业表现受到影响。相比之下，Lynkuet的作用机制更为创新：它同时靶向调节体温的NK1和NK3两个神经激肽受体，而Veozah只作用于NK3。武田宣布已正式终止与阿斯利康合作开发的神经系统疾病项目，原因是相关疗法在二期临床试验中未达预期。该合作项目聚焦于针对α-突触核蛋白的单克隆抗体药物，名为TAK-341或MEDI1341。武田曾在全球范围内开展一项涉及159例多系统萎缩症（MSA）患者的临床试验。MSA是一种罕见的神经退行性疾病，主要由脑内神经细胞逐渐丧失引起。试验采用每四周静脉输注抗体或安慰剂的方案，旨在评估药物在52周内对患者的神经功能改善情况，主要通过修订版的多系统萎缩评分量表（Modified Unified MSA Rating Scale）衡量。该临床试验未能达到预设的主要和次要终点。最初，武田与阿斯利康的合作协议涵盖了TAK-341在多系统萎缩症和帕金森病（PD）等神经退行性疾病中的研发。然而，随着最新研发管线的调整，武田已不再列出任何帕金森相关的临床项目。尽管如此，阿斯利康的二期开发管线中仍将α-突触核蛋白单抗列为重点目标。武田还暂停了两个处于一期临床阶段的项目，其中包括GDX012（也称TAK-012-1501），这是一种由武田通过收购GammaDelta Therapeutics于2021年开发的异体γδT细胞免疫治疗药物。该药物曾在急性髓性白血病（AML）患者中进行一期/二期联合试验，但由于公司今年早些时候宣布将细胞免疫疗法作为次要方向，未来前景变得不明朗。近年来，武田对细胞免疫领域的投入明显减少。此外，武田还宣布终止用于嗜睡症的danavorexton（也称TAK-925）开发。该药物为催产素-2受体激动剂，目前仍在二期临床阶段，用于呼吸系统疾病的研究。公司表示，已停止在嗜睡症上的一期临床试验，原因是“战略考虑”。这一决定与一年前因招募缓慢而暂停danavorexton在阻塞性睡眠呼吸暂停症（OSA）等适应症的二期试验类似。 GSK宣布将放弃其在抗癌领域的CD226轴相关项目，撤回所有剩余的二期临床试验。多年来，GSK曾寄希望于利用CD226分子构建下一代抗癌药物平台。CD226主要表达在T细胞和自然杀伤（NK）细胞表面，能与肿瘤细胞表面的CD155和CD112结合，激活免疫反应。然而，免疫系统中的其他检查点如CD96、PVRIG和TIGIT会干扰这一激活过程，增加了开发难度。早在2022年，GSK便将CD226轴视为“未来免疫肿瘤学的重要潜力领域”，并启动了多项相关研发项目，试图开发针对这些免疫检查点的抑制剂，期望实现数十亿英镑的市场潜力。但今年早些时候，GSK在抗TIGIT抗体belrestotug的合作开发中遭遇重大挫折，公司不得不计提4.71亿英镑（约6.29亿美元）的资产减值。今日公布的财报显示，除了belrestotug外，其他与CD226轴相关的项目也已终止。其中包括由iTeos和23andMe合作开发的抗CD96抗体Nelistotug（GSK6097608）。GSK曾在一项针对360名复发或转移性、PD-L1阳性头颈癌患者的二期临床试验中评估该药物。该试验于2023年启动，旨在检测Nelistotug联合GSK自主研发的免疫药物Jemperli，以及已停产的抗TIGIT药物belrestotug的联合疗效。另一项被终止的项目是GSK的抗PVRIG抗体GSK4381562，该药由GSK从Surface Oncology授权获得，曾进入二期临床开发阶段。公司还在进行一项涉及141例晚期实体瘤患者的一期试验，评估GSK4381562单药及联合用药的效果。除了肿瘤学，GSK还暂停了多个传染病相关的二期临床项目。例如，面向A、B、C、W和Y血清型的第二代脑膜炎疫苗GSK4023393，主要在婴幼儿中进行评估。该决定是在公司获得FDA批准另一款针对青少年和成人的MenABCWY疫苗（商品名Penmenvy）八个月后作出的。Penmenvy目前适用于10至25岁的青少年和成人，而GSK4023393则主要针对婴幼儿。公司还终止了一款针对巨细胞病毒（CMV）感染的重组亚单位疫苗的二期开发，以及在乳糜泻研究结束后，停止了TG2抑制剂GSK3915393在肺纤维化治疗中的临床试验。在一阶段试验方面，GSK也撤回了一款名为GSK4172239的DNA甲基转移酶1抑制剂。 Edesa公布了其因商业原因中止的呼吸衰竭临床3期试验的部分关键数据。结果显示，其抗TLR4抗体在改善新冠引发的急性呼吸窘迫综合征（ARDS）患者的生存率和康复方面，具有一定的潜力。此次试验共招募约100名患者，均为因新冠导致的ARDS患者，且接受了侵入性机械通气治疗。在试验中止前，所有参与者都接受了单次静脉注射候选药物paridiprubart（也称EB05）或安慰剂。根据公布的数据，28天内，接受paridiprubart治疗的患者死亡风险为39%，而对照组为52%。在60天的随访中，paridiprubart组的死亡率为46%，对照组为59%。公司认为，这一结果达到了其主要临床终点。因安全性问题，Incyte宣布暂停BET抑制剂的研发计划。去年，诺华在一项涉及骨髓纤维化药物pelabresib的三期研究中发现，急性髓性白血病（AML）发病率出现失衡，引发了对BET抑制剂安全性的担忧。作为收购MorphoSys的一部分，诺华获得了pelabresib，但这一发现导致其推迟BET抑制剂的上市计划，并使公司面临8亿美元的减值损失。今年早些时候，FDA对Vyne Therapeutics的一款BET抑制剂进行了1b期银屑病（斑块型银屑病）临床试验的暂停，原因是在一项非临床犬只试验中观察到睾丸毒性反应。Incyte在宣布放弃INCB57643时，并未提及任何安全性担忧，而是将决定归因于“研发资源的优先调整”。亲爱的读者，如果您对生物医药的最新动态感兴趣，或希望了解更多前沿生物科技资讯，请关注公众号。您的每一次关注和转发，都是最大的支持和鼓励！ 👉 关注大药时记，掌握更多前沿生物科技！ 👉 分享文章，让更多人受益！

免疫疗法临床2期临床3期上市批准临床结果

2025-10-29

·DrG的雍熙路

ICU里最凶险重症正被破解，III期临床数据展示重要临床获益

加拿大生物技术公司Edesa宣布了核心候选药物Paridiprubart（EB05）的III期临床结果，为急性呼吸窘迫综合症（ARDS）这一危重症医学的长期挑战带来了新的希望。临床数据显示，使用EB05显著降低患者死亡率，并减少有创机械通气或器官支持的使用比例，在极高风险患者中实现了突出且持久的生存获益。EB05的TLR4抑制机制代表了ARDS药物研发从“对症支持”到“免疫调控”的范式转变，靶向上游TLR4通路如同阻断炎症风暴的“总开关”，使EB05展现了前所未有的广谱治疗潜力。 (图源：shutterstock）危重症领域的“未爆弹”——急性呼吸窘迫综合征（ARDS）及其临床困境 ARDS是重症监护室（ICU）中最凶险的疾病之一，患者肺部因过度免疫反应引发炎症风暴，导致氧气无法进入血液，死亡率高达40%以上。全球每年有300多万ARDS患者，在中国多个 ICU 的研究中，ARDS 占 ICU 住院患者的比例约为 3.57%。当前的治疗方案主要以“肺保护性通气”为核心的支持性护理为主。尽管重症医学在通气技术方面取得了进步，但ARDS的死亡率仍维持在较高水平。大多数ARDS死亡病例并非单纯由呼吸衰竭引起，而是由多器官衰竭所致。ARDS的临床困境除了较高的死亡率，还包括长期依赖侵入性机械通气（IMV）的患者往往面临长期肺损伤以及生活质量下降等问题。因此，开发一种能够有效提高ARDS生存率、减少IMV和器官支持使用的创新药物，是重症治疗学领域的首要任务。然而ARDS药物的研发极其困难，此前针对单一炎症因子（如IL-6或TNF-α）的阻断疗法在临床上大多以失败告终。专家认为这与ARDS发病机制的高度生物学异质性以及炎症级联反应的复杂性有关，单一靶点难以有效中断病理进程。 Paridiprubart（EB05）创造免疫调控新范式 Edesa公司开发的单克隆抗体Paridiprubart（EB05）代表了一种全新的治疗策略，专注于调控先天免疫系统中的关键上游信号通路：Toll样受体4（TLR4）。 ARDS的病理基础是失调的免疫应答和过度炎症，即所谓的“细胞因子风暴”。TLR4是一种模式识别受体（PRR），广泛存在于巨噬细胞、树突状细胞等先天免疫细胞表面。它在识别外部病原体和内部组织损伤信号（DAMPs）中发挥核心作用。在急性损伤状态下，受损细胞会释放DAMPs。这些损伤分子被TLR4识别后，会激活一条强大的促炎级联反应轴。EB05特异性地结合并阻断TLR4的激活，旨在系统性地抑制由TLR4激活引发的整个促炎级联反应，这种机制设计巧妙地解决了ARDS异质性的难题。也就是说，EB05的疗效不受ARDS初始病因（病毒、细菌、创伤或其他）的限制，这种“威胁无关”（Threat-Agnostic）的广谱潜力改写了ARDS的治疗逻辑。多种病因引起的肺纤维化最终归结于由TLR4激活介导的信号通路（图片来源：Edesa Biotech） III期临床数据积极，EB05为ARDS治疗带来了真正意义的突破在Edesa公布的III期试验数据中，EB05在极高风险的危重症患者群体中展现了显著且持久的生存获益。该临床试验（NCT04401475）为一项随机、双盲、安慰剂对照研究，评估EB05联合标准治疗在伴有ARDS的COVID-19住院成年患者中的安全性和有效性，随后因转向评估更广泛的通用ARDS适应症而提前终止。但其意向治疗（ITT）的随机人群规模达到了104名患者（EB05组n=56，安慰剂组n=48），且该试验患者的基线风险极高，其28天和60天安慰剂组死亡率分别高达52%和59%。意味着该试验入组的患者大多处于重度ARDS状态，且普遍需要IMV支持。 EB05在该试验中成功达到主要和次要终点：安慰剂组的28天死亡风险为52%，而EB05治疗组为39%；60天的数据进一步证明了EB05生存获益的持久性，安慰剂组的死亡风险为59%，而EB05组为46%。 28天和60天的死亡率，n=104（图片来源：Edesa Biotech） EB05的临床价值还体现在对患者恢复速度的促进上。与安慰剂组相比，接受EB05治疗的受试者在28天时临床改善率（不再需要IMV和/或器官支持）提高了41%，从而促进了ICU资源的节约和患者医疗费用的降低。更重要的是，减少机械通气暴露时间，有助于降低呼吸机诱导的肺损伤及其后续的慢性肺纤维化风险，从而改善ARDS幸存者的长期发病率和生活质量。另外，在包括临床II期和III期在内的超过275名受试者中，EB05展示出一致且良好的耐受性。关键下一步，迈向更广泛的ARDS适应症一直以来，ARDS治疗缺乏有效的药物突破，相关研发的主要进展集中于优化支持性通气策略。Edesa首席执行官Par Nijhawan博士表示，该III期临床数据不仅验证了EB05的有效性，还彰显了其作为ARDS标准治疗的潜力，未来有可能将其适应症扩展到慢性呼吸系统疾病。值得注意的是，EB05已被美国政府生物医学高级研究与发展局（BARDA）选中，纳入由美国政府资助的临床试验，该试验旨在评估针对住院ARDS患者的三种新型“威胁无关”疗法。Edesa获得BARDA的资助和合作，为EB05在更广泛的ARDS人群中进行验证提供了资金支持和快速招募通道。另外，美国FDA已授予EB05快速通道（Fast Track）认定，并允许其采用“滚动提交”（Rolling Review）的方式提交上市申请，从而缩短EB05的上市时间。 EB05的未来商业成功和广泛应用将取决于其在更大、更具异质性的通用ARDS人群中的验证。根据 ClinicalTrials，Edesa将2027年11月列为 BARDA 试验数据的截止日期，如果该试验结果能够复制甚至超越本次III期临床的积极结果，EB05将有望彻底改变ARDS的临床管理模式。随着重症医学领域逐步进入精准免疫调控时代，Paridiprubart（EB05）的出现意味着，药物不再依赖针对特定病原体或炎症因子，而是通过重塑机体免疫反应实现广谱保护。这代表了一种从“被动救治”向“主动干预”的思维跃迁。未来，若EB05在后续注册性试验中继续验证其安全性与疗效，将能推动重症治疗从机械支持时代迈向分子精准治疗的新纪元。参考信源： 1. Edesa Biotech Reports Positive Results in Phase 3 Respiratory Study 2. NIH：Acute Respiratory Distress Syndrome 3. BARDA Selects Edesa Biotech's Drug for U.S. Funded Platform Trial in General ARDS 4. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03112-0?utm_source=chatgpt.com 免责声明 :本文所含的信息来源于文中可靠信源，仅供读者一般参考之用，不应作为决策依据，DrG的雍熙路对因使用本文内容而造成的一切损失，不承担任何责任。部分图片来源于网络，如涉及版权问题，敬请联系我们以便采相应处理举措。我们鼓励转发分享及合理引用本文内容，但请在引用时于明显位置标注文章来源。

临床结果临床3期临床2期临床成功

2025-10-28

·FierceBiotech

Edesa claims survival data win for phase 3 respiratory failure trial

Edesa Biotech rethought its plans in light of U.S. government support for paridiprubart.\n Edesa Biotech has shared data from its truncated phase 3 respiratory failure trial, linking the anti-TLR4 antibody to improvements in survival and recovery.The trial enrolled about 100 people who were hospitalized and on invasive mechanical ventilation before Edesa suspended the study on business grounds. Participants received single infusions of Edesa’s paridiprubart, also called EB05, or placebo to treat acute respiratory distress syndrome (ARDS) caused by COVID-19.After 28 days, the risk of death in the paridiprubart arm was 39% versus 52% in the placebo cohort. The 60-day risk of death was 46% on paridiprubart and 59% on placebo, which the biotech claimed as a primary endpoint win. Edesa also linked its drug candidate to improvements on a COVID-19 severity scale.The difference in 28-day mortality was smaller than in Edesa’s phase 2 trial. In the earlier, smaller study, the biotech reported (PDF) 28-day death rates of 7.7% for paridiprubart and 40% for placebo. The latest data come from a trial Edesa began before rethinking its plans in light of U.S. government support for paridiprubart. The Biomedical Advanced Research and Development Authority (BARDA) selected the drug candidate for inclusion in a platform trial of potential ARDS treatments last year. Edesa stopped enrollment in its phase 3 trial shortly after the news. Given the scope of the BARDA study, the biotech decided to shift its focus to general ARDS rather than cases caused by COVID-19. Edesa is now awaiting the results of the BARDA trial to inform the design of a phase 3 study supported by the Canadian government.Edesa has listed 2027 as the due date for data from the BARDA trial, citing a ClinicalTrials.gov entry with a primary completion date of November 2027. The biotech had $12.4 million to its name at the end of June, leading it to flag a substantial doubt about its ability to continue as a going concern.

临床3期临床2期临床结果

100 项与 NI-0101 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
成人呼吸窘迫综合征	临床3期	美国	Edesa Biotech, Inc.	2022-07-11
成人呼吸窘迫综合征	临床3期	加拿大	Edesa Biotech, Inc.	2022-07-11
成人呼吸窘迫综合征	临床3期	哥伦比亚	Edesa Biotech, Inc.	2022-07-11
急性呼吸窘迫综合征	临床3期	美国	Edesa Biotech, Inc.	2020-11-25
急性呼吸窘迫综合征	临床3期	加拿大	Edesa Biotech, Inc.	2020-11-25
新型冠状病毒感染	临床3期	美国	Edesa Biotech, Inc.	2020-11-25
类风湿关节炎	临床2期	美国	NovImmune SA	2017-05-10
类风湿关节炎	临床2期	波斯尼亚和黑塞哥维那	NovImmune SA	2017-05-10
类风湿关节炎	临床2期	保加利亚	NovImmune SA	2017-05-10
类风湿关节炎	临床2期	匈牙利	NovImmune SA	2017-05-10