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.
Ekene A Enemchukwu, Susan Kalota, Kaiser Robertson, Sijian Ge, Jingmei Lu, Hanh Badger, Salim Mujais, Kenneth M Peters
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引用次数: 0
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.
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.