Department of Urology, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
Department of Urology, Dongguk University Gyeongju Hospital, Dongguk University College of Medicine, Gyeongju, Korea.
BJU Int. 2018 Aug;122(2):283-292. doi: 10.1111/bju.14233. Epub 2018 May 4.
To evaluate the efficacy and safety of three dosing schemes of GV1001 in patients with benign prostatic hyperplasia (BPH).
Eligible patients were men aged ≥50 years, with an International Prostate Symptom Score (IPSS) of ≥13, maximum urinary flow rate (Q ) of 5-15 mL/s, post-void residual urine volume (PVR) of ≤200 mL, and prostate volume of ≥30 mL. After a 4 week run-in period, patients were randomly assigned to one of three treatment schedules: Group 1, GV1001 0.4 mg, 2-week interval; Group 2, GV1001 0.56 mg, 2-week interval; Group 3, GV1001 0.56 mg, 4-week interval) or placebo (Group 4). The eligible patients were administered GV1001 or placebo, for a total of seven intradermal injections that were administered at 2-week intervals at weeks 0, 2, 4, 6, 8, 10, and 12. Treatment continued for 12 weeks, and efficacy was evaluated at weeks 4, 8, 12, 13, and 16. Safety was evaluated throughout the 16-week period. The primary efficacy variable was change from baseline (CFB) in total IPSS. Secondary endpoints were CFB in Q , PVR, prostate volume, International Index of Erectile Function score, plasma testosterone level, dihydrotestosterone level, and prostate-specific antigen level.
A total of 161 patients were included (Group 1, n = 41; Groups 2-4, n = 40). Most patients (88.8%) received all planned doses of the study treatment. At week 13, a statistically significant difference in the mean CFB in IPSS was seen in GV1001 treatment Groups 1 and 2 vs the control group for the full analysis population (-3.5 [control] vs -7.2 and -6.8 in Groups 1 and 2, respectively; both P < 0.05). There were also statistically significant differences in CFB at weeks 8, 12, 13, and 16 in treatment Groups 1 and 2 vs control in the per-protocol population. There was a statistically significant reduction in prostate gland volume at week 16 vs control in all treatment groups (0.8 [control] vs -4.6, -2.5, and -4.2 mL in Groups 1-3, respectively; all P < 0.05). There were no statistically significant differences found in other secondary outcome measures. Adverse event (AE) reporting was similar across all four groups. No treatment-emergent AEs were considered to be related to the study drug.
The results indicate that GV1001 was effective and well tolerated, and may provide potential beneficial effects in patients with BPH. Compared with medical therapies that require daily dosing, the convenient dosing regimen of GV1001 may provide greater patient adherence. Further investigation of these observations will require large-scale clinical evaluation.
评估 GV1001 三种给药方案治疗良性前列腺增生（BPH）患者的疗效和安全性。
符合条件的患者为年龄≥50 岁、国际前列腺症状评分（IPSS）≥13、最大尿流率（Q ）为 5-15ml/s、剩余尿体积（PVR）≤200ml、前列腺体积≥30ml 的男性。经过 4 周的导入期后，患者被随机分配至以下三种治疗方案之一：第 1 组，GV10010.4mg，2 周间隔；第 2 组，GV10010.56mg，2 周间隔；第 3 组，GV10010.56mg，4 周间隔）或安慰剂（第 4 组）。合格患者接受 GV1001 或安慰剂治疗，共进行 7 次皮内注射，在第 0、2、4、6、8、10 和 12 周时每 2 周注射一次。治疗持续 12 周，在第 4、8、12、13 和 16 周评估疗效。整个 16 周期间评估安全性。主要疗效变量为总 IPSS 的从基线变化（CFB）。次要终点为 Q 、PVR、前列腺体积、国际勃起功能指数评分、血浆睾酮水平、二氢睾酮水平和前列腺特异性抗原水平的 CFB。
共有 161 名患者入选（第 1 组，n=41；第 2-4 组，n=40）。大多数患者（88.8%）接受了研究治疗的所有计划剂量。在第 13 周时，GV1001 治疗组 1 和 2 的 IPSS 平均 CFB 与对照组相比在全分析人群中具有统计学意义（-3.5[对照组] vs -7.2 和-6.8 在第 1 组和第 2 组，均 P<0.05）。在方案人群中，治疗组 1 和 2 在第 8、12、13 和 16 周时的 CFB 也具有统计学意义。与对照组相比，所有治疗组在第 16 周时前列腺体积均有统计学意义的减少（0.8[对照组] vs -4.6、-2.5 和-4.2ml 在第 1-3 组，均 P<0.05）。在其他次要终点测量中未发现统计学差异。所有四组的不良反应（AE）报告相似。没有发现与研究药物相关的治疗后出现的 AEs。
结果表明 GV1001 有效且耐受性良好，可能对 BPH 患者具有潜在的有益作用。与需要每日给药的医学治疗相比，GV1001 方便的给药方案可能会提高患者的依从性。需要更大规模的临床评估来进一步研究这些观察结果。
