Phase 1b Dose Escalation Study of Sozinibercept Inhibition of Vascular Endothelial Growth Factors C and D With Aflibercept for Diabetic Macular Edema.

IF 2.6 3区 医学 Q2 OPHTHALMOLOGY Translational Vision Science & Technology Pub Date : 2024-12-02 DOI:10.1167/tvst.13.12.32
David S Boyer, Nathan C Steinle, Joel A Pearlman, Cameron M Stone, Courtney Crawford, Sunil Gupta, Pravin U Dugel, Megan E Baldwin, Ian M Leitch
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Abstract

Purpose: Sozinibercept inhibits vascular endothelial growth factors (VEGFs) C and D. This study evaluated outcomes following switching from anti-VEGF-A monotherapy to intravitreal injections of three dose levels of sozinibercept in combination with aflibercept in patients with diabetic macular edema (DME).

Methods: A phase 1b, open-label, multicenter dose-escalation study with a 24-week follow-up. Patients received 3 loading doses of aflibercept (2 mg) in combination with sozinibercept (0.3, 1, or 2 mg) once every 4 weeks and were followed through week 24. The primary endpoint was safety, and secondary endpoints included mean change from baseline in best-corrected visual acuity (BCVA) and anatomic changes on imaging.

Results: Nine patients received sozinibercept in combination with aflibercept after a mean (SD) of 6.3 (2.4) injections of previous anti-VEGF-A. Sozinibercept combination therapy was well tolerated with no dose-limiting toxicities. Mean change in BCVA at week 12 was +7.7 letters (95% confidence interval [CI], 2-13.3) from baseline (65 letters [SD 5.5]) with a dose response for increasing doses of sozinibercept. At week 12, central subfield thickness (CST) was decreased by -71 µm (95% CI, -117 to -26) from baseline (434 µm [SD 58]), and 6 of 9 (67%) patients had a ≥50% reduction in excess foveal thickness.

Conclusions: In prior-treated patients with center-involved DME, switching to sozinibercept in combination with aflibercept was well tolerated with improved visual and anatomic outcomes.

Translational relevance: This first-in-human study builds upon basic research by providing safety and preliminary efficacy of sozinibercept (anti-VEGF-C/-D) in combination with aflibercept for DME.

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soziniberceept与afliberceept联合抑制血管内皮生长因子C和D治疗糖尿病黄斑水肿的1b期剂量递增研究
目的:Sozinibercept抑制血管内皮生长因子(vegf) C和d。本研究评估了糖尿病黄斑水肿(DME)患者从抗vegf - a单药治疗切换到三种剂量Sozinibercept联合阿非利西普玻璃体内注射的结果。方法:一项1b期、开放标签、多中心剂量递增研究,随访24周。患者每4周接受3次负荷剂量的aflibercept (2mg)与sozinibercept(0.3、1或2mg)联合治疗,随访至第24周。主要终点是安全性,次要终点包括最佳矫正视力(BCVA)与基线的平均变化和影像学解剖变化。结果:9例患者在既往抗vegf - a平均(SD)为6.3(2.4)次注射后接受sozinibercept联合aflibercept治疗。Sozinibercept联合治疗耐受性良好,无剂量限制性毒性。第12周时BCVA的平均变化为+7.7个字母(95%可信区间[CI], 2-13.3),与基线相比(65个字母[SD 5.5]),随着sozinibercept剂量的增加而出现剂量反应。在第12周,中央亚野厚度(CST)比基线(434 μ m [SD 58])减少了-71 μ m (95% CI, -117至-26),9名患者中有6名(67%)的过度中央凹厚度减少了≥50%。结论:在先前治疗过的中心累及性二甲双胍患者中,改用sozinibercept联合aflibercept耐受性良好,并且改善了视觉和解剖结果。翻译相关性:这项首次人体研究建立在基础研究的基础上,通过提供sozinibercept(抗vegf - c /-D)与aflibercept联合治疗二甲醚的安全性和初步有效性。
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来源期刊
Translational Vision Science & Technology
Translational Vision Science & Technology Engineering-Biomedical Engineering
CiteScore
5.70
自引率
3.30%
发文量
346
审稿时长
25 weeks
期刊介绍: Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.
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