Enemchukwu Ekene A, Kalota Susan, Robertson Kaiser, Ge Sijian, Lu Jingmei, Badger Hanh, Mujais Salim, Peters Kenneth M
Department of Urology, Stanford University School of Medicine, Stanford, California.
Arizona Urology Specialists, Tucson, Arizona.
J Urol. 2025 Apr;213(4):417-427. doi: 10.1097/JU.0000000000004373. Epub 2024 Dec 18.
We assessed efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca-activated K channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB).
Women, age 40 to 79 years, with OAB and urge urinary incontinence 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 end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume.
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, respectively; least-squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal = .017 and = .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 = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal = .026). Among patients receiving URO-902 24 mg, URO-902 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%).
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.
在一项针对膀胱过度活动症（OAB）女性的2a期安慰剂对照试验中，我们评估了URO - 902（一种表达大电导钙激活钾通道α亚基的研究性基因疗法）的疗效和安全性。
年龄在40至79岁之间、患有OAB且伴有急迫性尿失禁且对OAB药物治疗无效的女性，被随机分为单剂量24毫克和48毫克的URO - 902组或安慰剂组，通过在局部麻醉下经膀胱镜进行膀胱内注射给药。疗效终点包括从基线到第12周平均每日排尿次数、尿急发作次数、急迫性尿失禁发作次数以及患者报告的结果的变化。安全性评估包括不良事件和排尿后残余尿量。
在随机分组的80例患者中（URO - 902 24毫克组，n = 26；URO - 902 48毫克组，n = 27；安慰剂组，n = 27），74例接受了治疗，67例达到了第24周。在第12周时，与安慰剂相比，24毫克和48毫克的URO - 902组在每日排尿次数方面有显著改善（从基线的最小二乘均值变化分别为-2.3和-2.4，而安慰剂组为-0.8；最小二乘均值差异[95% CI]分别为-1.5 [-2.7至-0.3]和-1.6 [-2.8至-0.4]，名义p值分别为0.017和0.009）。与安慰剂相比，48毫克的URO - 902组在尿急发作次数（-3.4对-1.1；-2.2 [-4.0至-0.4]；名义p值 = 0.016）和患者总体变化印象有反应者的百分比（58%对31%；名义p值 = 0.026）方面有显著改善。在接受24毫克URO - 902、48毫克URO - 902和安慰剂的患者中，分别有46%、54%和54%经历了≥1次治疗中出现的不良事件，最常见的是尿路感染（0%、15%、4%）和血尿（6%、8%、8%）。
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有改善，且安全且耐受性良好。
