目的:为了评估疗效,安全,以及雷珠单抗生物相似物候选物(XSB-001)与参考产品(Lucentis®)的免疫原性,用于新生血管性年龄相关性黄斑变性(nAMD)。
方法:第三阶段,多中心,随机化,双面蒙面,平行组研究。
方法:nAMD患者。
方法:符合条件的患者被随机分配(1:1),每4周一次在研究眼中接受玻璃体内注射XSB-001或参考雷珠单抗(0.5mg[0.05mL]),共52周。疗效和安全性评估持续52周的治疗。
方法:主要终点是第8周早期治疗糖尿病视网膜病变研究(ETDRS)字母的最佳矫正视力(BCVA)从基线的变化。如果治疗组之间在第8周BCVA的最小二乘(LS)平均变化的差异的双侧90%CI(美国)或95%CI(世界其他地区)在±3.5字母的预定义等效界限内,则推断生物相似性。
结果:总计,582例患者(n=292XSB-001,n=290参考雷珠单抗)被随机分配。平均年龄74.1岁,大多数患者(85.2%)是白人,55.8%为女性。XSB-001和参考雷珠单抗组的基线平均BCVA评分为61.7和61.5ETDRS字母,分别。在第8周,XSB-001组中BCVA相对于基线的LS均值(SE)变化为4.6(0.5)ETDRS字母,参考雷珠单抗组中为6.4(0.5)字母(LS均值[SE]治疗差异:-1.8[0.7]ETDRS字母;90%CI,-2.9至-0.7;95%CI,-3.1至-0.5)。LS与基线的平均变化差异的90%CI和95%CI在预定义的等效范围内。在第52周,BCVA的LS均值(SE)变化为6.4(0.8)和7.8(0.8)字母,分别(LS平均[SE]治疗差异,-1.5[1.1]ETDRS字母;90%CI,-3.3至0.4;95%CI,-3.6至0.7)。在解剖学上的治疗之间没有临床意义的差异,安全,或到第52周的免疫原性终点。
结论:XSB-001在nAMD患者中表现出与参考雷珠单抗的生物相似性。用XSB-001治疗52周通常是安全的,耐受性良好,安全性与参考产品相似。
To evaluate the efficacy, safety, and immunogenicity of a ranibizumab biosimilar candidate (XSB-001) versus reference product (
Lucentis) for neovascular age-related macular degeneration (nAMD).
Phase III, multicenter, randomized, double-masked, parallel-group study.
Patients with nAMD.
Eligible patients were randomized (1:1) to receive intravitreal injections of XSB-001 or reference ranibizumab (0.5 mg [0.05 ml]) in the study eye once every 4 weeks for 52 weeks. Efficacy and safety assessments continued through 52 weeks of treatment.
Primary end point was change from baseline in best-corrected visual acuity (BCVA) by ETDRS letters at week 8. Biosimilarity was concluded if the 2-sided 90% confidence interval (CI) (United States) or 95% CI (rest of world) for the difference in least-squares (LS) mean change in BCVA at week 8 between treatment groups was within the predefined equivalence margin of ± 3.5 letters.
In total, 582 patients (n = 292 XSB-001, n = 290 reference ranibizumab) were randomized. Mean age was 74.1 years, most patients (85.2%) were White, and 55.8% were women. Mean BCVA score at baseline was 61.7 and 61.5 ETDRS letters in the XSB-001 and reference ranibizumab groups, respectively. At week 8, the LS mean (standard error [SE]) change in BCVA from baseline was 4.6 (0.5) ETDRS letters in the XSB-001 group and 6.4 (0.5) letters in the reference ranibizumab group (LS mean [SE] treatment difference: -1.8 [0.7] ETDRS letters; 90% CI, -2.9 to -0.7; 95% CI, -3.1 to -0.5). The 90% CI and 95% CI for LS mean difference in change from baseline were within the predefined equivalence margin. At week 52, LS mean (SE) change in BCVA was 6.4 (0.8) and 7.8 (0.8) letters, respectively (LS mean [SE] treatment difference, -1.5 [1.1] ETDRS letters; 90% CI, -3.3 to 0.4; 95% CI, -3.6 to 0.7). There were no clinically meaningful differences between treatments in anatomical, safety, or immunogenicity end points through week 52.
XSB-001 demonstrated biosimilarity to reference ranibizumab in patients with nAMD. Treatment with XSB-001 for 52 weeks was generally safe and well tolerated, with a safety profile similar to the reference product.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.