Gene Therapy With URO-902 (pVAX/hSlo) for the Treatment of Female Patients With Overactive Bladder and Urge Urinary Incontinence: Safety and Efficacy From a Randomized Phase 2a Trial.

IF 5.9 2区 医学 Q1 UROLOGY & NEPHROLOGY Journal of Urology Pub Date : 2025-04-01 Epub Date: 2024-12-18 DOI:10.1097/JU.0000000000004373
Ekene A Enemchukwu, Susan Kalota, Kaiser Robertson, Sijian Ge, Jingmei Lu, Hanh Badger, Salim Mujais, Kenneth M Peters
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Abstract

Purpose: We assessed 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, 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.

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, respectively; least-squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P = .017 and P = .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 = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P = .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%).

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.

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基因治疗eu -902 (pVAX/hSlo)治疗女性膀胱过动症和急迫性尿失禁:来自随机2a期试验的安全性和有效性
目的:在一项2a期安慰剂对照试验中,评估uroo -902的有效性和安全性。uroo -902是一种表达大电导Ca2+激活K+通道α亚基的基因疗法。材料和方法:40-79岁的OAB和急发性尿失禁(UUI)女性,对OAB药物难治,随机分为单剂量uro - 90224mg和48mg或安慰剂组,局部麻醉下经膀胱镜下肌内注射。疗效终点包括从基线到第12周的平均每日排尿、急症发作、UUI发作和患者报告的结果的变化。安全性评估包括不良事件(ae)和尿后残留量。结果:80例随机患者(uroo -902 24 mg, n=26;eu -902 48 mg, n=27;安慰剂组(n=27), 74人接受治疗,67人活到第24周。在第12周,与安慰剂相比,24和48 mg的URO-902在每日排尿方面有显著改善(基线的最小二乘平均变化,-2.3和-2.4 vs -0.8;最小二乘平均差[95%置信区间],-1.5[-2.7至-0.3]和-1.6[-2.8至-0.4],名义P分别=0.017和P=0.009)。与安慰剂相比,48 mg的eu -902在急症发作中有显著改善(-3.4 vs -1.1;-2.2[-4.0至-0.4];名义P=0.016)和患者对变化的总体印象应答者的百分比(58% vs 31%;名义P = 0.026)。在接受uro - 90224mg、48mg和安慰剂治疗的患者中,分别有46%、54%和54%的患者发生≥1次治疗性不良反应,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,使用eu -902治疗在疗效和患者报告的结果方面有所改善,并且安全性和耐受性良好。
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来源期刊
Journal of Urology
Journal of Urology 医学-泌尿学与肾脏学
CiteScore
11.50
自引率
7.60%
发文量
3746
审稿时长
2-3 weeks
期刊介绍: The Official Journal of the American Urological Association (AUA), and the most widely read and highly cited journal in the field, The Journal of Urology® brings solid coverage of the clinically relevant content needed to stay at the forefront of the dynamic field of urology. This premier journal presents investigative studies on critical areas of research and practice, survey articles providing short condensations of the best and most important urology literature worldwide, and practice-oriented reports on significant clinical observations.
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