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 Moderate 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）

2025-09-01·Ophthalmology science

HORNBILL: A First-in-Human Phase I/IIa Study of the Safety, Tolerability, and Early Pharmacodynamics of BI 764524 for Diabetic Macular Ischemia

Article

作者: Nassar, Khaled ; Sepah, Yasir J ; Pearce, Elizabeth ; Habib, Maged ; Krawczyk, Bartlomiej ; Jhaveri, Chirag ; Gliem, Martin ; Sivaprasad, Sobha ; Ahmed, Mohamed ; Simons, Gudrun ; Giani, Andrea ; Nguyen, Quan Dong

Objective:

To report safety and early pharmacodynamic results from a first-in-human trial of intravitreal (IVT) anti-semaphorin 3A antibody in participants with diabetic macular ischemia (DMI).

Design:

HORNBILL, a phase I/IIa study of BI 764524, comprised a nonrandomized, open-label, uncontrolled, single-rising-dose (SRD) and masked, randomized, sham-controlled, multiple-dose (MD) parts.

Participants:

Adults with DMI and stable diabetic retinopathy (DR) treated with pan-retinal photocoagulation and without center-involving diabetic macular edema.

Methods:

Twelve participants received single IVT doses of BI 764524 0.5 mg (n = 3), 1.0 mg (n = 3), or 2.5 mg (n = 6) in the SRD part. Thirty-one participants received 3 IVT doses of BI 764524 2.5 mg (n = 21) or sham procedures (n = 10) at 4-week intervals and were followed to week 22 in the MD part.

Main Outcome Measures:

The primary SRD end point was the number of participants with dose-limiting events; secondary end points assessed drug-related and ocular adverse events (AEs). The primary MD end point was the number of participants with drug-related AEs; secondary end points included changes from baseline in foveal avascular zone (FAZ) area, best-corrected visual acuity (BCVA), and central subfield thickness (CST).

Results:

No dose-limiting events or drug-related AEs were reported with SRD; the highest tested dose (2.5 mg) was selected for the MD part. In the MD part, 2 investigator-assessed drug-related AEs (vitreous floaters and increased gamma-glutamyl transferase) were reported. No intraocular inflammation or occlusive retinal vasculitis cases occurred. At week 12 (4 weeks after the final injection), the adjusted mean FAZ area change was -0.004 mm² in the BI 764524 group and +0.019 mm² with sham. At week 22 (14 weeks after the final injection), the adjusted mean FAZ area change was -0.001 mm² in the BI 764524 group and +0.010 mm² with sham. No relevant BCVA and CST changes occurred.

Conclusions:

HORNBILL met the primary safety end points; all evaluated BI 764524 doses were well tolerated. These findings support further investigation of BI 764524 in participants with DR and retinal nonperfusion.

Financial Disclosures:

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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）

2025-07-29

·生物制品圈

勃林格殷格翰 10 亿押注眼疾给药技术长效制剂成新焦点

摘要：德国制药巨头勃林格殷格翰近日与爱尔兰初创公司 Re-Vana Therapeutics 达成一项价值超 10 亿美元的合作协议，旨在利用后者的长效缓释注射平台开发新型眼疾疗法。这一合作不仅标志着勃林格正式加码眼科领域，更凸显了长效给药技术在减少眼部反复注射、提升患者依从性方面的巨大潜力，有望改写青光眼、黄斑变性等疾病的治疗模式。一、合作核心：长效平台破解眼科治疗痛点根据协议，勃林格将获得 Re-Vana 专有缓释注射技术的使用权，针对至少三个未披露的眼疾靶点开发创新疗法。Re-Vana 的核心技术是一种可注射聚合物载体，能将药物封装其中，在眼内缓慢释放达 6-12 个月，从根本上解决现有疗法需每月甚至每两周注射一次的弊端。“眼部反复注射不仅给患者带来痛苦，还可能增加感染、视网膜脱离等风险。”Re-Vana 首席科学官在声明中指出，其平台通过精准控制药物释放速率，在保证疗效的同时将注射频率降至每年 1-2 次。这一技术已在临床前研究中验证可行性，其基于再生元 Eylea（阿柏西普）开发的长效版本正处于 II/III 期试验，初步数据显示 6 个月给药一次的疗效不劣于每月注射。勃林格将支付未披露的首付款及研发资金，后续里程碑付款最高达 10 亿美元，同时获得合作产品的全球商业化权益。双方计划每年新增至多三个合作项目，逐步扩充眼科管线。二、勃林格的眼科野心：从追随者到破局者此次合作是勃林格布局眼科领域的关键一步。目前，该公司眼科管线仅有 4 款在研药物，包括针对糖尿病视网膜病变的 II 期抗体 BI 764524 和用于地理萎缩的 II 期抗体片段 BI 771716，均处于早期阶段，与诺华、罗氏等巨头相比差距明显。“眼科是勃林格‘未被满足医疗需求’战略的核心领域之一。” 勃林格全球研发负责人表示，选择 Re-Vana 的技术，正是看中其能快速弥补公司在给药技术上的短板。分析显示，全球眼科药物市场规模已达 400 亿美元，其中抗 VEGF 药物（如 Eylea、Lucentis）因需频繁注射，年销售额超 150 亿美元，而长效制剂若上市，可能抢占 30% 以上市场份额。三、技术突围：长效给药成眼科研发新赛道Re-Vana 的技术并非孤例，长效给药已成为眼科领域的研发热点。诺华的雷珠单抗缓释植入剂已在 III 期试验中证实可每 3 个月给药一次，罗氏也在开发玻璃体内植入式抗 VEGF 制剂，试图将注射间隔延长至 6 个月。但 Re-Vana 的聚合物平台具有独特优势：其载体材料可生物降解，无需手术取出，且能兼容小分子、抗体等多种药物类型。除眼疾外，该平台还可用于中枢神经系统疾病，这也是勃林格看中的潜在扩展方向。“我们的技术像‘生物注射器’，能在病灶处持续‘按需释放’药物。”Re-Vana 创始人强调。此次合作前，Re-Vana 已完成 1190 万美元 A 轮融资，投资者包括专注医疗技术的风投机构。其自主研发的双特异性抗体长效制剂也进入临床前阶段，适应症尚未披露。四、行业影响：给药技术重构市场格局眼科治疗长期受限于给药方式：滴眼液生物利用度不足 5%，玻璃体腔注射虽直接但依从性差。长效制剂的突破可能重塑竞争格局 —— 不仅能提升患者生活质量，还能通过减少就诊次数降低医疗成本。对勃林格而言，合作的成败将决定其能否在眼科市场实现 “弯道超车”。目前，该公司在呼吸、心血管等领域的传统优势面临专利悬崖，亟需新增长点。而 Re-Vana 若能借助巨头资源加速技术落地，也有望从小众初创公司跃升为给药技术领域的领军者。“这不是简单的技术授权，而是一场关于‘治疗体验革新’的豪赌。” 行业分析师指出，随着人口老龄化加剧，青光眼、年龄相关性黄斑变性患者激增，长效眼疾疗法的市场需求将持续释放。勃林格与 Re-Vana 的联手，或许只是这场变革的开始。五、未来挑战：疗效与安全性的平衡术尽管前景广阔，长效制剂仍需跨越多重障碍。药物释放速率的精准控制是核心难题 —— 释放过快可能引发毒性，过慢则可能导致疗效不足。Re-Vana 的聚合物载体虽在动物实验中表现稳定，但人体眼内微环境复杂，长期安全性（如炎症反应、载体降解产物影响）仍需大规模临床试验验证。此外，支付方的态度也至关重要。长效制剂的研发成本更高，定价可能高于现有疗法，能否通过 “减少注射相关并发症、降低总体医疗支出” 说服医保覆盖，将直接影响其市场渗透速度。无论如何，勃林格的 10 亿押注已为眼科长效给药技术注入强心剂。当治疗从 “频繁痛苦” 走向 “便捷长效”，患者将成为最终受益者 —— 而这场由技术创新驱动的变革，正悄然改变眼科疾病的治疗范式。参考来源：https://www.biospace.com/business/boehringer-links-with-irish-drug-delivery-start-up-re-vana-in-1b-eye-deal识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

引进/卖出临床2期临床3期

2025-07-29

·求实药社

超10亿美元！勃林格殷格翰与Re-Vana合作开发眼科长效疗法

来源：新猎药人笔记德国制药巨头勃林格殷格翰（Boehringer Ingelheim, BI）与爱尔兰药物递送初创公司Re-Vana Therapeutics达成了一项价值超过10亿美元的合作协议，旨在利用Re-Vana的眼科药物递送技术开发长效眼科疗法。根据协议，勃林格殷格翰将获得针对三个特定靶点的独家权利，并将向Re-Vana支付预付款、开发、监管和商业里程碑付款，仅针对最初的三个靶点，总潜在交易价值就可能超过10亿美元。此外，Re-Vana还将获得净销售额的特许权使用费。Re-Vana将协助勃林格殷格翰进行可行性研究和开发活动，直至勃林格殷格翰将相关药物推进至临床阶段。Re-Vana研发管线Re-Vana的药物递送技术旨在减少眼科患者定期接受注射的需求，能够将治疗药物缓慢释放到眼睛中，持续时间可达6至12个月。降低治疗负担可能会提高患者的治疗依从性，并可能带来更好的治疗效果。结束语：勃林格殷格翰的眼科研发管线目前包括四个处于2期临床试验阶段的资产，其中包括BI 764524（一种针对糖尿病视网膜病变的抗体）和BI 771716（一种针对地图样萎缩的抗体片段）。长效几乎将进一步增强勃林格殷格翰在眼科领域的领导地位。免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部。联系我们ICNS 2025展位火热预定中！扫码立即咨询电话：13816031174（同微信）赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。点击此处“阅读全文”咨询更多！

2025-07-28

·BioSpace

Boehringer Links with Irish Drug Delivery Start-Up Re-Vana in $1B+ Eye Deal

iStock, jozefmicic The German giant is looking to develop new drugs for undisclosed eye diseases using Re-Vana’s extended-release injectable platform to supply drugs to the eye for months at a time. Boehringer Ingelheim has formed a development partnership with U.S. and U.K.–based Re-Vana Therapeutics aimed at creating new long-acting therapies for eye diseases. The deal, announced Monday, includes an undisclosed upfront payment from Boehringer to Re-Vana, but developmental, regulatory and commercial milestone payments could push the deal’s value north of $1 billion based on an initial three targets, according to the announcement . The precise targets the partners will go after were also not disclosed, but Boehringer will be able to add up to three projects to its pipeline per year. The companies also did not share the length of the agreement. The collaboration combines Re-Vana’s extended-release drug delivery technology with potentially newly developed drugs to create what the companies called “first-in-class” therapies for the eye. Re-Vana’s platform aims to enable long acting drug delivery by injecting a polymer into the eye that slowly releases a drug over a period of six to 12 months, reducing the need for repeated injections into the eye. Boehringer doesn’t currently have any approved ophthalmic drugs, though it does have four candidates in development. Those include an unnamed vascular modulator in Phase I for an unannounced indication; BI 764524, an antibody for diabetic retinopathy in Phase II; and BI 771716, an antibody fragment in Phase II for geographic atrophy. BI 771716 is being developed with the Swiss firm CDR-Life, in a deal dating back to 2020. Founded in 2016, Re-Vana is a spinout of Queens University Belfast. After launching and closing an $11.9 million series A round in 2022 , the company is currently in the middle of a series B raise, according to an email sent to BioSpace . Though Re-Vana is establishing partnerships with larger pharmas based partially on its extended-release technology, it is also producing an internal pipeline, including a six-month extended-release version of Regeneron’s macular degeneration drug Eylea, which is in Phase II/III trials, as well as a six-month bispecific antibody in an undisclosed indication.

临床2期临床1期抗体药物偶联物

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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临床结果

适应症

分期

评价

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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)	願顧夢餘齋顧獵積壓繭 = 糧艱網衊鬱製繭願襯齋積顧遞鏇蓋網艱構鹽鹹 (遞顧範簾醖鹹觸餘選鏇, 艱觸壓範鹽顧衊壓鏇製 ~ 願製廠鏇遞膚鑰鬱襯願) 更多	-	2024-05-22
				BI 764524 (Single-rising Dose Part - Medium Dose BI 764524)	願顧夢餘齋顧獵積壓繭 = 鬱膚壓鏇築積艱齋遞簾積顧遞鏇蓋網艱構鹽鹹 (遞顧範簾醖鹹觸餘選鏇, 夢簾範鏇願鏇築夢繭遞 ~ 繭鑰鏇簾網襯襯獵廠願) 更多
NCT04424290 (HORNBILL, NEWS) 人工标引	临床1/2期	糖尿病黄斑缺血	43	BI 764524 (单次给药剂量递增部分)	壓鏇鬱夢獵顧觸膚齋艱(衊鹹觸夢糧糧淵憲憲簾) = 单次给药剂量递增部分，未报告。餘鬱鏇壓膚鹽廠衊範夢 (繭醖遞遞選壓襯壓憲鑰 ) 更多	积极	2024-05-10
				BI 764524 (多次给药部分)
NCT04424290 (HORNBILL, ARVO2024) 人工标引	临床1/2期	糖尿病黄斑缺血	12	BI 764524 0.5 mgBI 764524 0.5 mg	餘壓顧夢廠築壓壓襯製(膚積鏇範齋鹽襯淵醖製) = No DLEs were reported in the SRD part. 膚艱願鹽艱構鏇淵餘網 (餘願選積鹽齋鏇艱獵網 ) 更多	积极	2024-05-05
				BI 764524BI 764524 1.0 mg
NCT04424290 (HORNBILL, ARVO2024) 人工标引	临床1/2期	糖尿病黄斑缺血	31	BI 764524	淵蓋餘鑰簾夢獵積餘憲(鹽壓鹽網簾壓窪積鏇衊) = 鹹壓鬱餘願鑰鹹鏇餘齋選衊艱繭餘網願鹽蓋窪 (憲願襯願鑰廠鏇選構鬱 )	积极	2024-05-05
EURETINA2021	N/A	糖尿病黄斑缺血 \| 糖尿病性视网膜病变	-	BI-X 0.5 mg	繭網鹽夢襯製鏇壓鏇蓋(蓋鏇願餘壓鏇襯築製築) = 夢齋糧膚選襯積夢鑰夢憲獵築觸憲選鹹膚衊積 (願壓窪蓋製構築願簾憲 )	-	2021-09-01
				BI-X 1.0 mg	繭網鹽夢襯製鏇壓鏇蓋(蓋鏇願餘壓鏇襯築製築) = 餘選構鑰鏇願選齋襯鹽憲獵築觸憲選鹹膚衊積 (願壓窪蓋製構築願簾憲 )