Clinical Trial for the Assessment of Safety, Usability and Efficacy of the Vixe Combination for OAB in Female Subjects (XAVIER)

An Exploratory, Prospective, Multicenter, Randomized, Double Blind, Placebo + Sham Device Controlled, Study to Assess the Safety, Usability, and Initial Efficacy of the ViXe Combination for Intravesical Administration of XEOMIN® in the Treatment of Female Patients With Idiopathic Overactive Bladder (OAB)

The goal of this interventional clinical trial is to assess the safety, usability and initial efficacy of Xeomin and Vibe combination (ViXe) compared to placebo + sham in female subjects with idiopathic Overactive Bladder. The main question[s] it aims to answer are: • The rate of device and drug related serious adverse events during treatment and throughout the follow up period • Investigator, subject and technician satisfaction from treatment, and • Assess the initial efficacy of the drug-device combination compared to placebo-sham combination. Participants will be treated a single time with the ViXe combination and will be followed up for a period of 12 weeks, during which they will visit the clinic after 2, 6 and 12 weeks. Participants will complete a 3-day voiding diary prior to the 6- and 12-week FU visit.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Combination product: ViXe Xombination; Combination product: Placebo + Sham

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Coimbra, Portugal
    • CHUC
  • Guimarães, Portugal
    • HSOG
  • Lisboa, Portugal
    • CHLN
  • Porto, Portugal
    • CHUSJ
  • Porto, Portugal
    • Hospital Lusíadas
  • Porto, Portugal
    • Hospital Prelada
  • Setúbal, Portugal
    • Hospital Luz Setúbal
  • Vila Nova De Gaia, Portugal
    • CHVNG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female aged between 18 and 80 years at the time of signing the informed consent.
• Signed written informed consent.
• Diagnosis of OAB for at least 6 months prior to screening, determined by documented subject history.
• At least 8 voiding episodes/day based on 3-consecutive days voiding diary at screening.
• OAB with at least 6 leaking episodes associated with urgency (UUI), and at least one episode per day demonstrated on 3-consecutive days voiding diary.
• Subject is mentally competent with the ability to understand and comply with the requirements of the study.
• Subject is willing and able to initiate self-catheterization post treatment, if required.
• Subject with inadequate response to conservative medication treatment/s as defined by the investigator.
• Subject agrees to attend all follow-up evaluations and is willing and capable to fill out voiding diaries and questionnaires completely and accurately and is willing to complete required exams and tests.
• Females with childbearing potential must have a negative pregnancy test and must practice an acceptable method of birth control, from at least 4 weeks before treatment until 12 weeks after treatment

Exclusion Criteria:

• Previous participation in another study with any investigational drug or device within the past 90 days.
• Allergy to Botulinum neurotoxin type A or any of the other ingredients and components of this device or the drug
• Subject with OAB caused by neurological conditions (i.e., Myasthenia Gravis, ALS, Eaton-Lambert Syndrome, etc.)
• Any neurological disease or disorder including Alzheimer's, Parkinson, MS, stroke (CVA), neuropathy or injury resulting in neuropathy.
• Subject currently under treatment with biofeedback, pelvic muscle rehabilitation, pelvic floor physical therapy. If willing to discontinue will be allowed to participate after 4 weeks of wash out. Self-Kegels exercises are allowed.
• Bleeding disorders or treatment with anticoagulants, antiplatelet (except acetylsalicylic acid), or thrombolytic medications within 14 days prior to screening.
• Subjects with compromised respiratory function or dysphagia.
• Current or planned treatment with drugs that interfere with neuromuscular transmission (e.g., aminoglycoside, polypeptide antibiotics, lincomycin antibiotics, or aminoquinolines)
• Subject with known polyuria/polydipsia with 24-hour total volume void > 3000 ml.
• Subject with PVR ≥ 200 ml based on bladder ultrasound at screening visit.
• Current or recurrent urinary tract infection (3 or more infections in the last 6 months), or presence of urinary fistula per physical examination, or known significant urinary tract obstruction or urethral stricture.
• Subject who received botulinum toxin injections within the past 8 months.
• Subject with predominant stress incontinence based on MESA incontinence score and/or voiding diary at screening.
• BMI ≥ 35 kg/m2.
• If used, should be on stable doses of diuretics for the past 3 months.
• Subjects who have any implanted electronic devices (a pacemaker, for example), permanent or transient, that cannot be removed prior to the treatment.
• Subjects who have received tibial or sacral nerve stimulation (SNS) any time in the past or percutaneous tibial nerve (PTNS) in the last 3 months.
• Previous urinary incontinence surgery or prolapse surgery or de novo urinary incontinence post-surgery within the last 12 months.
• Any spinal surgery within the last 12 months.
• Previous abdominoperineal resection of the rectum or previous radical hysterectomy.
• Diagnosis of interstitial cystitis or bladder pain syndrome as defined by either American Urological Association (AUA) or European Association of Urology (EAU) guidelines.
• History of evidence of anatomic pelvic, urological or urogenital abnormality according to investigator's discretion.
• If used, subjects should be on stable dose of antimuscarinics and/or beta-3 adrenergic agonists for at least 3 months prior to enrolment and agree to remain on stable medication consumption until the 12-weeks follow-up visit.
• If used, subjects should be on a stable dose of tricyclic antidepressants, Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) for at least 3 months prior to enrolment and agree to remain on stable medication consumption until the 12 weeks follow-up visit.
• Subject with abnormal renal function defined by estimated glomerular filtration rate (eGFR) of 30 ml/min or less.
• History of pelvic radiotherapy or chemotherapy for pelvic malignancies.
• Diabetes with peripheral nerve neuropathy or severe uncontrolled diabetes (with HbA1C > 7.5%).
• Uterine prolapse, cystocele, enterocele or rectocele past the hymen.
• Deemed unsuitable for enrollment by the investigator based on history or physical examination.
• Any psychiatric or personality disorder at the discretion of the study physician.
• Any severe or uncontrolled systemic disease (e.g., cardiac, renal, pulmonary, hepatic, or gastrointestinal), malignant tumor, or medical history of HIV infection, or any findings from laboratory or physical examination performed at screening at the discretion of the investigator
• Subject is breastfeeding
• Drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ViXe Combination; This arm includes a combination of the Xeomin medication, a generic of the Botulinium Toxin A drug that is not currently approved for this indication, and the Vibe medical device, an experimental device for the delivery of Botulinium Toxin to the bladder for overactive bladder	Combination product: ViXe Xombination; Combination of Xeomin and the ultrasound based delivery system (Vibe) for intravesical administration of the drug in a minimally invasive procedure
Placebo Comparator: Placebo + Sham; The placebo that will be used in the study is identical in its physical properties to the investigational drug and will be used in the same manner as the active drug. Sham procedure will include all the steps for device preparation and activation, without the actual transmission of ultrasound eneregy to the participant.	Combination product: Placebo + Sham; Placebo identical in package and appearance to Xeomin together with all steps of Vibe device preparation and activation, but without the actual operation of the ultrasound energy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events Rate	Incidence of drug and device related adverse events from treatment to 12-weeks post treatment	12 weeks
Usability and ease-of-use perception by investigator, subject and technician	Satisfaction of investigator, participant and technicain from the treatment, as assessed by the sponsor designed usability questionnaire. Investigator's questionnaire consists of 43 questions on a scale of 1-7 each (total range 43-301). The higher the total score, the better the investigator satisfaction. Subject usability questionnaire consists of 11 questions on a scale of 0-10 (total range 0-110). Thr higher the score, the more statisfied the subject from the treatment. Technician's questionnaire consists of yes/no questions only.	Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Urgency Urinary Incontinence	Mean change from baseline in the average number of daily Urgency Urinary Incontinence (UUI) Episodes at 6 and 12-weeks post treatment based on a 3-day voiding diary	12 weeks
Total Daily Episodes	Mean change from Baseline in the average number of daily voiding episodes at 6 and 12-weeks post treatment based on a 3-day voiding diary	12 weeks
Urinary Urgency	Mean Change from baseline in Urinary grade 3 or 4 Urgency Episodes at 6 and 12-weeks post treatment based on a 3-day voiding diary	12 weeks
Voiding Leaks	Mean change from baseline in Number of large leaks at 6 and 12-weeks post treatment based on a 3-day voiding diary	12 weeks
Nocturia	Mean change from baseline in the average number of daily Nocturia episodes at 6 and 12-weeks post treatment based on a 3-day voiding diary	12 weeks
Quality of Life Queationnsaire	Change from baseline in OAB-q (Overactive Bladder - quality) total score at week 12. OAB-q is a two-domain questionnaire (symptom bother and health related quality of life), each of which is a 100-point scale. Higher scores reflect higher quality of life.	12 weeks

Collaborators and Investigators

• Sponsor: Vensica Therapeutics Ltd.
• Collaborators: Blueclinical, Ltd.
• Investigators: Principal Investigator: Palma dos Reis, Dr, Principal investigator at CHLN

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2023
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive
• Other Study ID Numbers: ViXe-CLP-0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All subjects will be assigned a unique study code that will not enable anyone outside of the study team on site to identify them. No personal data will be colected during the study other than date of birth.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No