CRIMSON: A Multicentre, Randomised, Sham-controlled (and Active Controlled in the USA), Double-masked, 72-week Trial to Study the Safety, Tolerability, Pharmacokinetics, and Efficacy of 3 Dosing Regimens of Intravitreal BI 764524 in Patients With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy

This study is open to adults with diabetic retinopathy. People who have non-proliferative diabetic retinopathy of moderate or high severity can join the study.
The purpose of this study is to find out whether a medicine called BI 764524 helps people with diabetic retinopathy. The study also aims to find a suitable treatment plan for BI 764524. Participants are put into 5 groups by chance. Participants in groups 1, 2, and 3 get BI 764524. Over 1 year, they get a different number of injections of the same dose of BI 764524 injected into 1 eye. During some visits, participants may get a sham control, which is done like an eye injection but without a needle, so that participants will not know how many injections of BI 764524 they received. Participants in group 4 only get a sham control. Participants in group 5 (only in the USA) get aflibercept or sham injections during some visits. Aflibercept is a medicine already used to treat diabetic retinopathy.
Participants are in the study for one and a half years. During this time, they visit the study site at least 16 times. During this time, doctors regularly do eye exams and visual tests to assess the severity of participants' eye condition. After 1 year of treatment, researchers look at the number of participants with eye improvements. To do so, they compare eye damage and certain severe eye problems between the groups of participants. The doctors also regularly check participants' health and take note of any unwanted effects.

开始日期2024-05-15

申办/合作机构

Boehringer Ingelheim GmbH

NCT04424290

/ Completed临床1/2期

A First-in Human Trial to Study Safety and Tolerability of Single Rising Intravitreal dOses (Open Label, Non-randomized, Uncontrolled) and in Addition the Early Biological Response of Multiple intravitReal Dosing (Single-masked, raNdomized, Sham-controlled) of BI 764524 in panretinaL Photocoagulation (PRP) Treated proLiferative Diabetic Retinopathy (PDR) Patients With Diabetic Macular Ischemia (DMI) - the HORNBILL Study

This is a study in people with a type of diabetic eye disease called diabetic retinopathy with diabetic macular ischemia. People who have had laser treatment for their diabetic retinopathy can participate in the study. The laser treatment is called panretinal photocoagulation.
The purpose of the study is to find out how well different doses of a medicine called BI 764524 are tolerated. BI 764524 is injected into the eye. The study has 2 parts. In the first part, participants get different doses of BI 764524 only once. Participants are in the first part for about 5 months and visit the study site about 8 times. In the second part, participants are put into different groups by chance. Some participants get BI 764524 injections every 4 weeks. Other participants get sham injections every 4 weeks. A sham injection means that it is not a real injection and contains no medicine. Participants cannot tell whether they get the real injection or a sham injection. For the second part, participants are in the study for about 7 months. During this time, they visit the study site about 7 times. In this study, BI 764524 is given to humans for the first time.
The doctors compare how well people tolerate the BI 764524 injections and the sham injections.
The doctors also regularly check the general health of the participants.

开始日期2020-06-12

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-764524 相关的临床结果

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100 项与 BI-764524 相关的转化医学

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100 项与 BI-764524 相关的专利（医药）

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项与 BI-764524 相关的文献（医药）

Trials

HORNBILL: a phase I/IIa trial examining the safety, tolerability and early response of BI 764524 in patients with diabetic retinopathy and diabetic macular ischaemia—rationale, study design and protocol

Article

作者: Giani, Andrea ; Pearce, Elizabeth ; Chong, Victor ; Nguyen, Quan Dong ; Sepah, Yasir

Abstract:

Background:

Diabetic macular ischaemia (DMI) is a complication of diabetic retinopathy that leads to irreversible vision loss. DMI is characterised by reduced retinal vessel density and enlargement of the foveal avascular zone (FAZ). Despite its clinical burden, there is no formal consensus on the definition of DMI, and no approved treatment. Semaphorin 3A (Sema3A) is an axonal guidance molecule that blocks revascularisation of the ischaemic retina. Sema3A modulation is therefore a promising mechanism of action for the treatment of ischaemic eye diseases. BI 764524 is an intravitreal anti-Sema3A ischaemia modulator agent.

Methods:

HORNBILL (NCT04424290) is a phase I/IIa trial comprising a non-randomised, open-label, single rising dose (SRD) part and a randomised, masked, sham-controlled multiple dose (MD) part to investigate the safety, tolerability and early biological response of ischaemia modulator BI 764524 in adults (≥18 years) with DMI. DMI will be defined using optical coherence tomography angiography (OCTA) as either any degree of disruption in the retinal vascularity (SRD) or a FAZ of ≥0.5 mm2 (MD). Subjects in the SRD part will receive 0.5, 1.0 or 2.5 mg of BI 764524; the maximum tolerated dose will then be used in the MD part. A minimum of 12 subjects will be enrolled into the SRD part; planned enrollment is 30 for the MD part. The primary endpoint of the SRD part is the number of subjects with dose-limiting adverse events (AEs) until day 8. The primary endpoint of the MD part is the number of subjects with drug-related AEs from baseline to end of study, and secondary endpoints include change from baseline in the size of the FAZ, best-corrected visual acuity and central retinal thickness.

Discussion:

DMI is a poorly defined condition with no treatment options. HORNBILL is the first clinical trial to assess a treatment for DMI and to use OCTA as a means to define and examine DMI. The OCTA data generated in this trial could form the basis of formal diagnostic criteria for DMI. Furthermore, the novel mechanism of action (Sema3A modulation) explored in this trial has the potential to revolutionise the treatment landscape for patients with DMI.

Trial registration:

ClinicalTrials.govNCT04424290; EudraCT 2019-004432-28. Registered on 9 June 2020

项与 BI-764524 相关的新闻（医药）

2024-05-12

·药明康德

12项创新疗法公布积极早期临床数据...… | 一周盘点

▎药明康德内容团队编辑本期看点1. Freeline Therapeutics公司公布了其用于治疗戈谢病的在研基因疗法FLT201的早期疗效数据，一次治疗就能显著改善患者的疲劳程度，提升其日常活动能力。2. 5款治疗眼部疾病的创新疗法公布积极早期临床数据，涉及基因疗法、细胞疗法、单克隆抗体疗法和小分子光控开关药物。3. 再生元（Regeneron Pharmaceuticals）用于治疗遗传性耳聋的在研基因疗法DB-OTO使1名11个月大的患者的听力在接受治疗24周内恢复到了正常水平。图片来源：123RFFLT201：公布1/2期临床试验的新数据 Freeline Therapeutics公司公布了其在研基因疗法FLT201进行中的1/2期GALILEO-1试验的最新临床数据。FLT201是一种潜在“first-in-class”与“best-in-class”的在研腺相关病毒（AAV）基因疗法，用于治疗1型戈谢病成年患者。该疗法旨在提供一次性治疗，以持续增加患者体内GCase表达并减少有害底物的积累，阻止疾病进展，让患者不必终生接受治疗。FLT201采用Freeline的AAVS3衣壳，将新型基因引入肝细胞，生产经过理性设计的GCase变体。在临床前研究中，该GCase变体在溶酶体pH条件下的半衰期比野生型人类GCase增加了20倍以上。在临床前研究中，FLT201可导致GCase高度表达并减少关键组织中的底物。此次公布的结果显示，FLT201能显著降低此前曾长期使用获批疗法且葡萄糖基神经酰胺（lyso-Gb1）水平持续较高的1型戈谢病患者的lyso-Gb1水平，该指标是临床应答的最佳预测指标之一。此外，患者的骨髓负担和疲劳方面也出现了初步的改善迹象。安全性方面，FLT201具有良好的安全性和耐受性，未出现输注反应或严重不良事件。一些患者的谷丙转氨酶（ALT）水平轻微升高，但通过免疫疗法进行控制后，对疗效没有影响。ATSN-201：公布1/2期临床试验的新数据 Atsena Therapeutics公司公布了其在研基因疗法ATSN-201用于治疗X连锁视网膜劈裂症（XLRS）的1/2期临床试验的新数据。ATSN-201使用的新型扩散衣壳AAV.SPR能够横向扩散到视网膜下注射点以外的位置，实现对中央视网膜的安全和有效的基因递送（在XLRS患者的视网膜中，分裂腔主要集中在中央视网膜部位）。此前的研究显示，AAV.SPR在临床剂量下能够有效递送载荷至视网膜中央凹上的视锥细胞，无需手术分离，并且不会引起炎症。此次公布的数据显示，首个队列（低剂量组）的3名患者中有两名在给药8周后开始出现视网膜分裂的广泛改善。第24周（目前可获得的最新时间点）时，分裂仍在继续改善。在视网膜下注射点内外都发现了分裂腔的改善区域，这表明AAV.SPR正在从注射点横向扩散，与这种新横向扩散衣壳的预期特征一致。在视网膜结构改善的相同位置也观察到了功能改善。一名患者的视力改善高达14 dB，其中38个位置的视力改善超过7 dB。美国FDA认为，在≥5个预先指定的位置至少改善7 dB是具有临床意义的。该组所有3名XLRS患者对ATSN-201的耐受性良好，未报告严重不良事件。DB-OTO：公布1/2期临床试验的初步数据再生元公布了其用于治疗遗传性耳聋的在研基因疗法DB-OTO的1/2期临床试验的初步积极结果。DB-OTO是一种在研细胞选择性AAV基因疗法，旨在通过AAV载体将OTOF基因的健康拷贝传递至耳蜗毛细胞，为因OTOF基因突变导致的先天性深度听力损失患者提供持久的生理性听力。此前，DB-OTO已获得了FDA的孤儿药资格、罕见儿科疾病认定以及快速通道资格。一名患者在11个月大时就接受了DB-OTO治疗，在24周内听力恢复到正常水平，而另一名在4岁时接受该疗法的患者也在治疗后6周时初步观察到听力有所改善。这两名儿童都因OTOF基因变异而在出生时患有严重的遗传性耳聋，其中接受治疗的11个月大儿童是全球最早接受基因疗法治疗遗传性耳聋的患者之一。HORA-PDE6b：公布1/2期临床试验数据 Coave Therapeutics公司新成立的子公司eyeDNA Therapeutics宣布，其用于评估HORA-PDE6b的1/2期临床试验24个月时的随访结果良好。HORA-PDE6b是一种以AAV5为载体的基因疗法，用于治疗PDE6b基因双等位基因突变引起的视网膜色素变性。此次公布的结果显示，在接受高剂量治疗且症状较轻的患者亚组中，在24个月时报告了在最佳矫正视力（BCVA）和Goldmann视野（GVF）结果方面的积极疗效。未治眼睛的BCVA与基线相比增加了0.09 LogMar，而经治眼睛的视力保持稳定（+0.02 LogMar）。从基线开始，未治眼睛的GVF平均减少了超过300 deg²，而经治眼睛则相对稳定。低剂量组患者（n=7）在五年期间的长期数据发现，未治眼睛的BCVA持续下降（从第二年开始每年增加0.05到0.08 LogMAR），这与疾病的自然病程相符。与此同时，同一组中经治眼睛的BCVA与基线相比保持稳定，在同样的随访期内仅增加了0.03到0.06 LogMAR）。第5年时，经治眼睛与未治眼睛与基线相比的BCVA平均变化的差距为0.25 LogMAR（12个字母）。此外，用于评估视杆细胞功能的蓝光全视野刺激测试（FFST）持续显示出经治眼睛的光感知阈值有改善的趋势，具有临床意义。临床关注亚组在随访12个月时观察到的积极视网膜解剖学评估趋势保持到了随访24个月时。在24个月的研究期后，患者对高低两种剂量的HORA-PDE6b耐受性都很好。发生了5例眼部严重不良事件（SAE），包括2例可能与HORA-PDE6b相关的已解决的SAE（1例脉络膜视网膜炎和1例视力下降）。这些患者未接受预防性口服皮质类固醇。NGN-401：公布1/2期临床试验的初步数据 Neurogene公司公布了其用于治疗Rett综合征的基因疗法NGN-401的1/2期临床试验的初步安全性和耐受性数据。NGN-401是一种在研AAV基因疗法，递送表达全长人甲基胞嘧啶结合蛋白2（MeCP2）的转基因。NGN-401利用Neurogene专有的基因调控技术，提供高度控制和一致的MeCP2表达，从而避免了与常规基因治疗相关的过表达相关毒性。在临床相关剂量的NGN-401非临床研究中，Rett综合征的主要特征得到改善，未观察到过表达毒性。此次公布的结果显示，在接受治疗后约9个月、6个月和3个月的随访中，3名患者对NGN-401的耐受性普遍良好。所有与NGN-401相关的不良事件均为轻度或1级，并且是短暂或可消退的。大多数不良事件是AAV的已知潜在风险，未报道任何MeCP2过表达毒性的体征或症状。RG6501（OpRegen）：公布1/2a期临床试验的新数据 Lineage Cell Therapeutics公司公布了其同种异体视网膜色素上皮（RPE）细胞疗法RG6501（OpRegen）用于治疗年龄相关性黄斑变性（AMD）继发地理萎缩（GA）的1/2a期临床试验的24个月的数据。结果显示，接受OpRegen细胞后至少2年内，患者眼睛的视网膜外层结构和视觉功能获得了持续的改善，OpRegen细胞可以通过抵消宿主RPE细胞功能障碍和损失来为GA区域内剩余的视网膜细胞提供支持。与基线值相比，队列4中的10名患者的BCVA在接受治疗后24个月时平均增加了5.5个字母，其中5名OpRegen覆盖GA病变更广的患者的治疗效果更好，BCVA平均增加了7.4个字母。经光学相干断层扫描（OCT）检查发现，OpRegen覆盖GA病变更广的患者的视网膜外层结构持续得到改善。FT819、FT522：公布1期临床试验的初步数据Fate Therapeutics公司宣布，其现货型CD19靶向嵌合抗原受体（CAR）T细胞疗法FT819用于治疗系统性红斑狼疮的1期临床试验完成了首例患者的输注。此外，该公司还公布了FT819治疗复发/难治性B细胞恶性肿瘤（BCM）的1期研究数据，及现货型CD19靶向CAR自然杀伤细胞（NK）细胞疗法FT522治疗复发/难治性B细胞淋巴瘤（BCL）的1期研究的初步临床观察结果。结果显示，FT819和FT522均能诱导快速、深度和持续的CD19+ B细胞耗竭。ACE1831：公布1期临床试验的初步数据Acepodia公司公布了其现货型CD20靶向抗体偶联异体γδ2 T细胞疗法ACE1831用于治疗非霍奇金淋巴瘤的1期剂量递增试验的初步数据。ACE1831利用γδ T细胞上高表达的NK细胞激活受体来清除恶性血细胞，在体外和体内模型中都显示出了对癌细胞增强的细胞毒性。此次公布的结果显示，ACE1831单次给药（最低剂量）治疗后，5名患者中有1名出现完全缓解（CR），3名达到了疾病稳定（SD）。在这些患者中，1名CR和2名SD患者曾接受过CD19靶向CAR-T细胞疗法。在ACE1831单次给药后的三个月内，观察到了持续的临床缓解。最低剂量的ACE1831耐受性良好，没有出现与ACE1831相关的严重不良事件，包括移植物抗宿主病（GVHD）、神经毒性、高级别细胞因子释放综合征（CRS）或剂量限制性毒性反应。BI 764524：公布1/2a期临床试验数据勃林格殷格翰（Boehringer Ingelheim）公司公布了其靶向Sema3A的人源化单克隆抗BI 764524的积极1/2a期临床试验数据。新闻稿指出，该研究是首个探索糖尿病黄斑缺血（DMI）潜在疗法的研究。BI 764524旨在重建缺血区域的血管并减少视网膜的渗漏，为解决视网膜疾病中的视网膜非灌注问题提供了可能性。研究发现，BI 764524在玻璃体内单剂量和多剂量给药后耐受性良好，达到了主要安全性终点，并显示出潜在疗效的早期迹象。该研究在第16周达到了预先指定的早期疗效标准，即与假手术相比FAZ的面积稳定（p<0.2）。在短期试验期内，其他次要疗效终点未显示出相关变化。KIO-301：公布1/2期临床试验的新数据Kiora Pharmaceuticals公司公布了其用于治疗视网膜色素变性的小分子光控开关（Photoswitch）KIO-301的1/2期临床试验的新数据。KIO-301能够选择性地赋予视网膜神经节细胞（RGC）光敏能力，旨在绕过退化的光感受器将神经信号传递到大脑。此前患者报告的结果表明，在注射KIO-301后，其感知光的能力、描绘明暗对比的能力以及整体视觉功能都有所改善。并且在研究过程中没有报告不良事件，包括眼部不良事件。此次公布的结果显示，在所有评估的时间点，接受治疗患者的大脑视觉处理中心中的神经活动比基线有统计学上的显著增加，且基线时视力较好患者的神经活动增加更明显。与先前报道的视野、视力和功能性视力的改善一致，这种大脑活动的增加是时间依赖性的。▲患者大脑视觉处理中心中的神经活动较基线时显著增加（图片来源：参考资料[8]）CK-4021586（CK-586）：公布1期临床试验数据Cytokinetics公司公布了其用于治疗射血分数保留型心力衰竭（HFpEF）的心脏肌球蛋白抑制剂CK-4021586（CK-586）的1期临床试验的初步数据。CK-4021586是一种新型、选择性、口服小分子心肌酶抑制剂，旨在减轻HFpEF引起的心肌过度收缩。在临床前模型中，CK-586通过减少心脏收缩过程中活性肌球蛋白交叉桥的数量，从而降低收缩力，减轻了心脏的过度收缩。该1期研究达到了主要终点，表明CK-586在健康受试者中的安全性和耐受性良好，且具有线性的药代动力学特征。使用超声心动图评估的药效学结果与预期一致。研究中未观察到严重不良事件，且尚未达到停药标准。这些数据支持CK-586进入2期临床试验，预计将于2024年第四季度启动。▲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（可上下滑动查看）[1] EyeDNA Therapeutics Announces Positive 24-month Data Presented at ARVO from Ongoing Phase I/II Trial of HORA-PDE6b Gene Therapy in Patients with Retinitis Pigmentosa Caused by Bi-allelic Mutations in PDE6b. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/07/2876355/0/en/EyeDNA-Therapeutics-Announces-Positive-24-month-Data-Presented-at-ARVO-from-Ongoing-Phase-I-II-Trial-of-HORA-PDE6b-Gene-Therapy-in-Patients-with-Retinitis-Pigmentosa-Caused-by-Bi-a.html[2] Neurogene Presents Favorable Safety Data from Phase 1/2 Trial of NGN-401 Gene Therapy for Rett Syndrome during ASGCT Annual Meeting. Retrieved May 10, 2024, from https://www.businesswire.com/news/home/20240507803994/en[3] Cytokinetics Announces Topline Data From Phase 1 Clinical Study of CK-4021586. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/08/2877723/35409/en/Cytokinetics-Announces-Topline-Data-From-Phase-1-Clinical-Study-of-CK-4021586.html[4] Neurocrine Biosciences Announces Initiation of Phase 1 Clinical Study Evaluating Effects of NBI-1117567 in Healthy Adults. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-initiation-of-phase-1-clinical-study-evaluating-effects-of-nbi-1117567-in-healthy-adults-302138590.html[5] OpRegen® (RG6501) Phase 1/2a Clinical Study 24-Month Visual Acuity Results Featured at 2024 Retinal Cell & Gene Therapy Innovation Summit. Retrieved May 10, 2024, from https://www.businesswire.com/news/home/20240506017390/en[6] Acepodia Announces Preliminary Clinical Data From Phase 1 Clinical Trial of ACE1831, First-Ever Anti-CD20 Antibody Conjugated Allogenic Gamma Delta T Cell Therapy for Non-Hodgkin's Lymphoma. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/acepodia-announces-preliminary-clinical-data-from-phase-1-clinical-trial-of-ace1831-first-ever-anti-cd20-antibody-conjugated-allogenic-gamma-delta-t-cell-therapy-for-non-hodgkins-lymphoma-302139302.html[7] Boehringer Ingelheim shares positive results from the first study worldwide in diabetic macular ischemia. Retrieved May 10, 2024, from https://www.globenewswire.com/en/news-release/2024/05/06/2875619/0/en/Boehringer-Ingelheim-shares-positive-results-from-the-first-study-worldwide-in-diabetic-macular-ischemia.html[8] Kiora Pharmaceuticals Reports Additional Clinical Data for KIO-301 Showing a Statistically Significant Increase in Brain Activity in the Visual Cortex in Patients with Retinitis Pigmentosa. Retrieved May 10, 2024, from https://www.newsfilecorp.com/release/208051[9] VYNE Therapeutics Announces FDA Clearance of IND Application for VYN202, a Novel BD2-Selective BET Inhibitor. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/06/2875779/0/en/VYNE-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-VYN202-a-Novel-BD2-Selective-BET-Inhibitor.html[10] BioAtla Announces FDA Clearance of Investigational New Drug Application for BA3361, a CAB-Nectin-4 Antibody Drug Conjugate for the Treatment of Multiple Tumors. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/06/2875781/0/en/BioAtla-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-BA3361-a-CAB-Nectin-4-Antibody-Drug-Conjugate-for-the-Treatment-of-Multiple-Tumors.html[11] Eisbach Bio announces FDA clearance of IND application for EIS-12656, a first-in-class allosteric inhibitor of ALC1. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/eisbach-bio-announces-fda-clearance-of-ind-application-for-eis-12656-a-first-in-class-allosteric-inhibitor-of-alc1-302136665.html[12] Mediar Advances First-in-Class Fibrosis Portfolio to the Clinic with First Cohort Dosing in Phase 1 trial of MTX-463 and Establishes Clinical Advisory Board. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/mediar-advances-first-in-class-fibrosis-portfolio-to-the-clinic-with-first-cohort-dosing-in-phase-1-trial-of-mtx-463-and-establishes-clinical-advisory-board-302136287.html[13] 한미약품, 차세대 비만 ‘삼중작용제’ 1상 “FDA IND 승인” . Retrieved May 10, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=21860[14] Biotheryx Announces U.S. FDA Clearance of Investigational New Drug Application for BTX-9341, a First-In-Class, Dual Bifunctional Degrader of CDK4/6. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/biotheryx-announces-us-fda-clearance-of-investigational-new-drug-application-for-btx-9341-a-first-in-class-dual-bifunctional-degrader-of-cdk46-302137704.html[15] Fate Therapeutics Announces First Lupus Patient Treated in Phase 1 Autoimmunity Study of Off-the-shelf FT819 CAR T-cell Program. Retrieved May 10, 2024, from https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-announces-first-lupus-patient-treated-phase-1[16] Atsena Therapeutics Announces Positive Clinical Data from the First Cohort of Phase I/II Trial Evaluating ATSN-201 Gene Therapy for the Treatment of X-linked Retinoschisis (XLRS). Retrieved May 10, 2024, from https://pipelinereview.com/atsena-therapeutics-announces-positive-clinical-data-from-the-first-cohort-of-phase-i-ii-trial-evaluating-atsn-201-gene-therapy-for-the-treatment-of-x-linked-retinoschisis-xlrs/[17] Freeline Presents Positive New Data from Phase 1/2 Trial of FLT201, Its Novel Gene Therapy Candidate for Gaucher Disease, in Late-Breaking Oral Presentation at ASGCT 27th Annual Meeting. Retrieved May 9, 2024 from https://freeline.life/freeline-presents-positive-new-data-from-phase-1-2-trial-of-flt201-its-novel-gene-therapy-candidate-for-gaucher-disease-in-late-breaking-oral-presentation-at-asgct-27th-annual-meeting-2/[18] LATEST DB-OTO RESULTS SHOW DRAMATICALLY IMPROVED HEARING TO NORMAL LEVELS IN A CHILD WITH PROFOUND GENETIC DEAFNESS WITHIN 24 WEEKS AND INITIAL HEARING IMPROVEMENTS IN A SECOND CHILD AT 6 WEEKS. Retrieved May 8, 2024 from https://investor.regeneron.com/news-releases/news-release-details/latest-db-oto-results-show-dramatically-improved-hearing-normal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

基因疗法免疫疗法临床结果

2024-05-10

·美通社

勃林格殷格翰发布全球首项糖尿病黄斑缺血研究的积极结果

德国殷格翰 2024年5月10日 /美通社/ -- 近日，勃林格殷格翰发布了BI 764524的I/IIa期研究HORNBILL的积极数据，该研究是首个探索糖尿病黄斑缺血（DMI）治疗选择的研究。研究发现，BI 764524单次和多次玻璃体内给药后耐受性良好，研究达到其主要安全性终点，并显示出潜在疗效的早期迹象 [1] 。 DMI是糖尿病视网膜病变（DR）的一种常见的、不可逆的并发症，可能导致失明 [1],[2],[3],[4] 。当中央视网膜的感光组织长时间未能获得足够的血液供应时，就有可能发生DMI。DMI目前尚无获批疗法。当前，晚期DR的标准治疗包括玻璃体内抗VEGF治疗或侵入性激光治疗。然而，一些患者尽管接受了这些治疗，病情仍出现进展 [5] 。BI 764524的作用机制新颖，通过抑制Sema3A通路使缺血区域血管再生，可能克服抗VEGF和激光治疗的局限性 [1] 。斯坦福大学医学院拜尔斯眼科研究所眼科及医学和儿科学教授兼本试验的主要和协调研究者Quan Dong Nguyen（MD, MSc, FARVO, FASRS）表示，"HORNBILL研究的结果非常鼓舞人心。研究结果表明可能存在一条早期干预途径，这条途径可能降低糖尿病视网膜病变患者发生危及视力的不可逆并发症（如DMI）的风险，甚至可能预防这种并发症的发生。视网膜无灌注是糖尿病视网膜病变患者发生视力丧失的关键驱动因素。然而，在HORNBILL研究之前，尚未将视网膜无灌注作为潜在治疗靶点进行探索。" 勃林格殷格翰视网膜健康负责人Ulrike Graefe-Mody（Ph.D.）表示，" 视网膜疾病（如糖尿病视网膜病变和DMI）带来的视力丧失对生活质量具有破坏性影响。今天分享的研究结果是在实现我们愿景的方向上迈出的重要一步，我们的愿景是开发精准治疗方案，在不可逆损伤发生之前，在正确的时间为正确的患者提供正确的治疗，以阻止视力丧失。我们将启动一项IIb期研究，进一步探索BI 764524的安全性和疗效。" HORNBILL是在2024年视力与眼科研究协会 (ARVO) 年会上勃林格殷格翰展示的23篇摘要之一，这23篇摘要涵盖了勃林格殷格翰的视网膜健康项目组合，包括视网膜无灌注和糖尿病视网膜病变、地图状萎缩和新生血管性年龄相关性黄斑变性的其他研究。关于 HORNBILL 研究 HORNBILL研究由两部分组成（单次给药剂量递增[SRD]：N=12；多次给药[MD]：N=31），两部分均达到其主要安全性终点，即发生剂量限制性不良事件（SRD）和治疗相关不良事件（MD）的患者人数 [1] 。该研究还达到了其预设的早期疗效标准，即第16周时中心凹无血管区面积相较于假注射组达到稳定状态（p<0.2） [1] 。这表明BI 764524可能对改善视网膜无灌注产生积极影响，并且可能阻止微血管进一步缺失 [1] 。即将进行的CRIMSON试验是一项IIb期试验，旨在进一步评估BI 764524在DR患者中的安全性和疗效，该研究将在今年晚些时候开始招募受试者。关于试验（ NCT04424290 ）这项I/IIa期试验评估了BI 764524在既往接受过全视网膜光凝术治疗的糖尿病视网膜病变（DR）伴糖尿病黄斑缺血（DMI）患者中的耐受性 [1] 。本试验包括两部分，首先进行单次给药剂量递增（SRD）部分，随后进行多次给药（MD）部分，BI 764524的给药途径为玻璃体内注射 [1] 。单次给药剂量递增部分在非随机、开放性、SRD部分，12例患者接受了玻璃体内BI 764524给药，剂量如下：0.5（n=3）、1.0（n=3）或2.5 mg（n=6） [1] 。主要终点是发生剂量限制性事件（DLE）的患者人数；次要终点是发生药物相关不良事件（AE）和任何眼部AE的患者人数 [1] 。 SRD部分患者的平均年龄为61.8岁 [1] 。SRD部分未报告DLE [1] 。4例患者的研究眼发生5起眼部AE，均与研究药物不相关。最高试验剂量（BI 764524 2.5 mg）确立了安全性，因此应用于MD部分 [1] 。多次给药部分在随机、设盲、假注射对照、MD部分，31例患者每隔4周（基线、第4周和第8周）共接受三次玻璃体内BI 764524 2.5 mg给药（n=21）或假注射（n=10），随后接受为期14周的随访，直至第22周研究结束 [1] 。主要终点是发生药物相关AE的患者人数；次要终点包括发生眼部AE的患者人数、中心凹无血管区（FAZ）面积较基线的变化，最佳矫正视力（BCVA）和中央视网膜厚度（CRT） [1] 。 MD部分患者的平均年龄为59.5岁 [1] 。7例患者发生眼部AE（研究眼；BI 764524组3例患者发生4起AE，假注射组4例患者发生6起AE），其中1起AE被报告为与研究药物相关（玻璃体飞蛾症） [1] 。此外，还发生1起全身性AE（研究者认为事件加重与研究药物相关）。无眼内炎症或闭塞性视网膜血管炎病例 [1] 。基线时，平均BCVA为65.2个字母，平均FAZ面积为0.65 mm，平均CRT为252 mm [1] 。HORNBILL研究达到了预设的早期疗效标准，即第16周时FAZ面积相较于假注射组达到稳定状态（p<0.2）。在较短的试验期内，其他次要疗效终点未显示相关变化。关于 BI 764524 BI 764524是一种人源化单克隆抗Sema3A抗体，预期可使缺血区域的血管再生，并减少视网膜渗漏，有望解决视网膜疾病中的视网膜无灌注问题。该化合物由勃林格殷格翰发现并开发，是该公司视网膜疾病研发项目组合的一部分。关于糖尿病视网膜病变和糖尿病黄斑缺血每3例糖尿病患者中就有1例受到糖尿病视网膜病变的影响，该疾病构成了工作年龄段成人视力丧失的主要原因。这是一种发病率不断增长的流行病，预计其发病率会随着全球糖尿病发病率的升高而不断增长。糖尿病黄斑缺血（DMI）是糖尿病视网膜病变的一种并发症，可能引起缓慢进展的不可逆视力丧失。参考文献 [1] Nguyen QD, Jhaveri C, Habib MS.Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024.Abstract number: 959 [2]Marques IP, et al. Diabetes 2019;68:648–653 [3] Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 [4] Tey KY, et al. Eye Vis (Lond) 2019;6:37 [5] Ip MS, et al. Ophthalmology 2014;122:367–374 关于勃林格殷格翰勃林格殷格翰是全球领先的生物制药企业，布局人用药品、动物保健两大业务领域。公司研发投入位居行业前列，致力于研究突破性疗法，解决巨大未满足的医疗需求，从而帮助改善或延长生命。自1885年成立以来，勃林格殷格翰一直是独立的家族企业，始终着眼长远发展，将可持续发展理念贯穿全价值链。公司在全球有超过5.35万名员工，服务逾130个市场，致力于打造一个更健康、更可持续、更公平的未来。更多详情，请访问： www.boehringer-ingelheim.com

临床2期临床1期临床结果

2024-05-06

·BioSpace

Boehringer Ingelheim shares positive results from the first study worldwide in diabetic macular ischemia

Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1 DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4 It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI. The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1 “The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.” “Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.” HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration. About the HORNBILL study The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year. Notes to Editors: About the trial (NCT04424290) This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1 Single rising dose part In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1 Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1 Multiple dosing part In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1 Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1 At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change. About BI 764524 BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions. About diabetic retinopathy and diabetic macular ischemia Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss. About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at Boehringer Ingelheim’s Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. References 1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959 2 Marques IP, et al. Diabetes 2019;68:648–653 3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 4 Tey KY, et al. Eye Vis (Lond) 2019;6:37 5 Ip MS, et al. Ophthalmology 2014;122:367–374

临床结果临床2期

100 项与 BI-764524 相关的药物交易

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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
非增殖性糖尿病视网膜病变	临床2期	美国	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	日本	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	德国	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	匈牙利	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	意大利	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	波兰	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	西班牙	Boehringer Ingelheim GmbH	2024-05-15
非增殖性糖尿病视网膜病变	临床2期	英国	Boehringer Ingelheim GmbH	2024-05-15
糖尿病黄斑缺血	临床2期	美国	Boehringer Ingelheim GmbH	2020-06-12
糖尿病黄斑缺血	临床2期	英国	Boehringer Ingelheim GmbH	2020-06-12

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适应症

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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


NCT04424290 (HORNBILL \| PO388 HORNBILL, CTgov)	临床1/2期	糖尿病黄斑缺血 \| 伴有糖尿病的增殖性视网膜病变	45	BI 764524 (Single-rising Dose Part - Low Dose BI 764524)	選顧遞鹽範廠蓋簾醖獵 = 遞窪鏇醖網壓範壓顧觸夢製襯觸糧鑰構積鹹選 (觸範衊衊鏇網築製艱製, 鏇遞襯齋襯顧憲餘鏇顧 ~ 蓋襯廠鑰鏇糧鹹夢餘淵) 更多	-	2024-05-22
				BI 764524 (Single-rising Dose Part - Medium Dose BI 764524)	選顧遞鹽範廠蓋簾醖獵 = 遞製齋繭築獵窪膚選糧夢製襯觸糧鑰構積鹹選 (觸範衊衊鏇網築製艱製, 範鹹蓋襯積製築構衊簾 ~ 糧糧簾蓋廠鏇鏇餘艱淵) 更多
EURETINA2021	N/A	糖尿病黄斑缺血 \| 糖尿病性视网膜病变	-	BI-X 0.5 mg	窪廠簾餘齋膚醖製鹽遞(觸鹹鹹壓網選淵窪醖獵) = 襯繭積繭範願遞憲糧簾選遞顧獵觸夢網構醖鏇 (願遞簾憲夢顧遞夢簾鬱 )	-	2021-09-01
				BI-X 1.0 mg	窪廠簾餘齋膚醖製鹽遞(觸鹹鹹壓網選淵窪醖獵) = 構鹹蓋淵鹽窪淵鏇築齋選遞顧獵觸夢網構醖鏇 (願遞簾憲夢顧遞夢簾鬱 )