PURPOSE To assess efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca2+-activated K+ channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB). MATERIALS AND METHODS Women, 40‒79 years, with OAB and urge urinary incontinence (UUI) who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection via cystoscopy under local anesthesia. Efficacy endpoints included change from baseline to week 12 in mean daily micturitions, urgency episodes, UUI episodes, and patient-reported outcomes. Safety assessments included adverse events (AEs) and postvoid residual urine volume. RESULTS Of 80 patients randomized (URO-902 24 mg, n=26; URO-902 48 mg, n=27; placebo, n=27), 74 received treatment, and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least squares mean change from baseline, -2.3 and -2.4 vs -0.8; least square mean difference [95% confidence interval], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P=0.017 and P=0.009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal P=0.016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P=0.026). Among patients receiving URO-902 24 mg, 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥1 treatment-emergent AEs, most commonly urinary tract infection (0%, 15%, 4%) and hematuria (6%, 8%, 8%). CONCLUSIONS In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated.

中文翻译：

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URO-902 （pVAX/hSlo） 基因治疗膀胱过度活动症和急迫性尿失禁女性患者：来自随机 2a 期试验的安全性和有效性。


目的 在膀胱过度活动症 （OAB） 女性的 2a 期安慰剂对照试验中评估 URO-902 的疗效和安全性，URO-902 是一种表达大电导 Ca2+ 激活的 K+ 通道的 α 亚基的研究性基因疗法。材料和方法 OAB 药物难治性 40\u201279 岁患有 OAB 和急迫性尿失禁 （UUI） 的女性被随机分配到单剂量 URO-902 24 和 48 mg 或安慰剂组，在局部麻醉下通过膀胱镜通过trusendos内注射给药。疗效终点包括平均每日排尿次数、尿急发作、UUI 发作和患者报告结局从基线到第 12 周的变化。安全性评估包括不良事件 （AEs） 和排尿后残余尿量。结果 80 例患者随机分组 （URO-902 24 mg，n=26;URO-902 48 毫克，n=27;安慰剂，n=27），74 例接受治疗，67 例达到第 24 周。在第 12 周时，与安慰剂相比，URO-902 24 和 48 mg 的每日排尿量显著改善相关（相对于基线的最小二乘平均变化，-2.3 和 -2.4 对 -0.8;最小二乘均数差 [95% 置信区间]，\u20121.5 [\u20122.7 至 \u20120.3] 和 \u20121.6 [\u20122.8 至 \u20120.4]，名义 P=0.017 和 P=0.009）。与安慰剂相比，URO-902 48 mg 与紧急发作的显著改善相关（\u20123.4 vs \u20121.1;\u20122.2 [\u20124.0 至 \u20120.4];名义 P=0.016）和患者对变化的总体印象反应者的百分比（58% vs 31%;名义 P=0.026）。在接受 URO-902 24 mg、48 mg 和安慰剂的患者中，分别为 46%、54% 和 54% 出现 ≥1 治疗中出现的 AE，最常见的是尿路感染 （0%、15%、4%） 和血尿 （6%、8%、8%）。 结论 在这项 2a 期试验中，与安慰剂相比，URO-902 治疗在疗效和患者报告的结果方面与改善相关，并且安全且耐受性良好。