Clinical readiness of Uzap - the minimally invasive Overactive Bladder treatment

摘要 膀胱过度活动症（OAB）严重影响美国12%以上的成年人口 - 大约3000万人（欧文等人，2006年）。紧迫和频繁的排尿冲动，性唤起 从睡眠，有时失禁，导致巨大的心理和经济成本， 导致仅在美国估计每年的经济负担就超过700亿美元（Reynolds，et al.， 2016）。目前的OAB干预措施多种多样，包括药物，神经刺激器， 肉毒杆菌毒素注射和手术方法，所有这些都有不良副作用， 缺乏广泛和持久的疗效。此外，药物治疗需要长期给药， 其它治疗可能需要重复的临床干预。 Stellartech研究公司正在开发用于经尿道的NewUro Uzap器械 射频粘膜分割它是唯一一种微创，单次，非药物， 用于缓解OAB症状而不损害排尿功能的非植入治疗。 研究表明，在膀胱粘膜模型中， 活动过度（Kanai等人，2007年）。这导致了类波固有的放大传播 电活动和机械活动，预期通过最低限度的 通过Uzap对粘膜隔离线进行侵入性热消融。Uzap背后的创新 该系统已获得7项授权专利。整体Uzap消融的初步研究 猪膀胱和组织样本显示对激动剂的收缩反应降低。 成功的临床前安全性和性能测试已在体外完成，并在 活体猪模型。在第一阶段，快速通道提案旨在证明长期 Uzap治疗的体内安全性和耐久性，以及在第2阶段，1）进行长期动物试验 安全性和有效性研究; 2）优化系统和电极设计和可用性以及制造 验证和确认单元; 3）执行验证和确认测试;持有预IDE （试验用器械豁免）会议，并提交IDE申请，以便将来进行首次临床试验。 30例女性难治性膀胱过度活动症伴尿失禁患者的人体试验。的 提出的严格工作将为将Uzap推进到临床阶段奠定坚实的基础， 走向商业化，以提供救济数以百万计的病人，并消除需要 用于植入或重复性临床干预。

Abstract Overactive bladder (OAB) severely impacts over 12% of the adult population in the United States – roughly 30 million people (Irwin, et al., 2006). Pressing and frequent urges to urinate, arousal from sleep, and sometimes incontinence, result in immense psychosocial and financial costs, leading to an estimated annual economic burden of >$70B in the US alone (Reynolds, et al., 2016). Current OAB interventions are varied and include pharmaceuticals, neurostimulators, botulinum toxin injections, and surgical approaches, all of which have adverse side effects and lack widespread and enduring efficacy. In addition, drug therapies require long-term dosing and other treatments can require repeat clinical interventions. Stellartech Research Corporation is developing the NewUro Uzap device for transurethral radiofrequency mucosal partitioning. It is the only minimally-invasive, single-session, non-drug, non-implant therapy for alleviating the symptoms of OAB without compromising voiding function. Research has shown excessive electrical connectivity within the bladder mucosa in models of overactivity (Kanai et al., 2007). This results in exaggerated propagation of wave-like intrinsic electrical and mechanical activity, which is anticipated to be amenable to therapy by minimally invasive thermal ablation of mucosal isolation lines by the Uzap. The innovations behind the Uzap system are already covered by 7 granted patents. Preliminary studies of Uzap ablation on whole pig bladder and tissue specimens demonstrated reduced contractile response to agonists. Successful preclinical safety and performance tests were completed in ex vivo and preliminary in vivo porcine models. This Fast-Track proposal seeks, in Phase 1, to demonstrate long-term in vivo safety and durability of Uzap therapy, and, in Phase 2, to 1) perform a long-term animal safety and efficacy study; 2) optimize system and electrode design and usability and fabricate Verification and Validation units; 3) perform Verification and Validation tests; hold a pre-IDE (Investigational Device Exemption) meeting and submit an IDE application for a future First-In- Human trial of 30 female patients with refractory overactive bladder with incontinence. The rigorous work proposed will create a firm base for advancing the Uzap to the clinical phase and towards commercialization, in order to provide relief for millions of patients and eliminate the need for implants or repetitive clinical interventions.