Non-invasive Saphenous Nerve Stimulation Therapy for Overactive Bladder

The objective of this study is to assess that Saphenous nerve (SAFN) stimulation with theNiNA System is at least non‐inferior to the use of tolterodine tartrate 4 mg extendedrelease (ER), taken daily in reducing the number of daily urgency urinary incontinence(UUI) episodes.The investigational device is the NiNA System which includes a wearable neurostimulatordevice with a stimulation matrix having 6 conductive gel pads that allow patients toprovide targeted neurostimulation by adjusting stimulation field geometry ("NiNA" or"Device"), a flexible wrap to secure the neurostimulator and stimulation matrix to theupper calf during treatment, and a smartphone‐based control application with patientsupport features ("NiNA App") or an alternate smartphone‐based control application withpatient support features and educational content ("NiNA Care App").The active control in the study is Tolterodine tartrate 4 mg capsules, extended‐release(ER) capsules, taken daily, which are indicated for the treatment of individuals havingOAB with symptoms of urinary incontinence, urgency, and frequency.The study design is a Prospective, dual center, randomized, adaptive, decentralized trialof the NiNA System vs an active control.The study will enroll up to 290 participants, based on an adaptive design withprospectively planned sample size re‐estimation (SSR) when 50% of the minimal estimatedtotal study cohort (i.e., 108 of 216 participants combined across the InvestigationalDevice Group & Active Control Group) has achieved the primary endpoint of 12 weeks.Participants will be randomized 1:1 to receive therapy using the investigational device(NiNA with NiNA App) or the active control. In the investigational device arm,participants will stimulate the SAFN for 30 minutes daily during a 28‐day NiNA therapyinduction phase and then for 30 minutes, 3‐times a week during therapy maintenance whichis provided beyond the induction phase, to maintain potential therapeutic benefit. Oncethe primary endpoint at 12 weeks is reached, investigational device arm Participants willcontinue with the maintenance phase therapy until the end of the study at 52 weeks.In the active control arm, participants take tolterodine tartrate ER (4 mg), daily for 12weeks. After 12 weeks, participants in this arm cross‐over and are treated with theinvestigational device therapy. The cross‐over group will be randomized 1:2 at the timeof crossover to either: 1. the investigational device (NiNA) and the NiNA App, that provides therapy remindersand allows user to control the Device; or, 2. the investigational device (NiNA) and an app that additionally has multimediaeducational content (NiNA Care App).Upon crossover at 12 weeks, participants will immediately begin an induction stimulationschedule (30 minutes daily for 28 days) with no washout of the active control drug.Following the 28‐days induction phase, the post‐crossover cohorts will transition to amaintenance schedule (30 minutes of stimulation for 3‐days per‐week) until the end of thestudy at 48 weeks.Participant compliance and adherence with the NiNA therapy will be assessed at variousstudy time points using the compliance and recordkeeping features associated with theinvestigational Device software app and a Study App.Active control (tolterodine) compliance and adherence through the primary endpoint (12weeks) will be assessed using standard digital clinical study measures such as amedication diary in the Study App.