Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy

Study Overview
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Brief Summary
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The aim of the SUISSE MPC 2 study is to treat stress urinary incontinence in adult women.

Detailed Description
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Stress urinary incontinence is the loss of small amounts of urine associated with coughing, laughing, sneezing, exercising or other movements that increase pressure on the abdomen and therefore increasing the pressure on the bladder. The goal of the SUISSE MPC2 study is to treat SUI in women using their own autologous muscle precursor cells. To guarantee enough outcome data, a sufficient number of patients will be enrolled to complete the study with 70 patients. The study will last approximately 8-9 months per patient. Each patient's baseline measurements serve as comparison for the treated measurements. Patients will participate in the study for up to approximately 8 to 9 months, including a baseline visit for screening, a visit to obtain a muscle biopsy up to 12 weeks later, an injection of MPCs up to 5 weeks later, and follow-up visits after 1, 3 and 6 months post injection. The injection is performed with ultrasound guidance using an endocavity ultrasound probe mounted on an Injection Device specifically designed for the clinical trial. All patients will be treated with one of the two doses of MPCs, assigned according to the study's randomization method. Half of the participating patients will receive the cell therapy that was previously studied in the completed phase I study. The other half of the participants will receive a higher dose of the cell therapy to investigate the effects of dose increase. Both groups of patients will be additionally monitored by medical examinations performed by clinicians to ensure the safety of the treatment. Furthermore, separate to the Principal Investigator, safety events will be reported to and investigated by the independent Data Safety Monitoring Board consisting of independent physicians and experts in the field. Data regarding the functionality and safety of the Injection Device will also be collected.

Official Title
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Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy

Conditions
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Female Stress Urinary Incontinence

Intervention / Treatment
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* Biological: autologous muscle precursor cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Predominant clinical diagnosis of SUI Stress incontinence ≥ grade I for at least 6 months Patient has at least once been treated with, and failed prior conservative treatments Patient had no improvement of SUI symptoms for at least 6 months before enrollment Patients with a certain amount of leaks or /and a predefined pad weight at screening Candidate for a surgical treatment Negative blood test: Human immunodeficiency virus (HIV 1/2), Hepatitis B HBsAg, Anti HBc, Hepatitis C, Anti-HCV-Ab and Syphilis Negative laboratory or blood test, and medical examination to eliminate risk of sexually transmitted diseases (STD) per investigators' discretion Competent to comprehend, sign, and date informed consent form before any study-specific procedure is performed Able to communicate well with the Investigator, and to understand and comply with the requirements of the study including answering the required questionnaires Exclusion Criteria: History of anti-incontinence surgery or prolapse surgery. Prolapse Diagnosed Hypermobile Urethra Previous diagnosis of any of the following conditions, disorders, or diseases of the urinary tract: Clinically significant cystocele or rectocele Ureteric bladder, urethral or rectal fistula Uncorrected congenital abnormality leading to urinary incontinence Interstitial cystitis Urinary urgency that results in leakage (as a predominant symptom) Adult enuresis Urodynamically proven detrusor instability or detrusor sphincter dyssynergia (DSD) Sensory urgency defined as first sensation of bladder fill (urge to void) of <100 ml No sensation at any time during the simple filling cystometry procedure Known urethral Stenosis (ureterocystoscopy) or urethral diverticulum History of cancer (< 5 year of remission) or history of pelvic radiotherapy Immunosuppressed patients Women who are pregnant or become pregnant during the course of the study, breast feeding or <12 months postpartum Untreated symptomatic urinary tract infection Fever (as defined by ≥ 38,5°C, axillar measurement), any infectious disease, cold or flu within the last 7 days Unstable severe systemic disease including uncontrolled hypertension, unstable angina, or myocardial infarction, severe coagulation disorders, bleeding diathesis, emboli, thrombophlebitis, infectious diseases, poor wound healing, and poorly controlled diabetes mellitus within 6 months before enrolment Known allergy/intolerance to at least one of the active ingredients or excipients of the investigational products Known allergy/intolerance to Penicillin or Streptomycin. Known genetically determined or acquired muscular disease, known neurological disorder (Parkinson's disease, multiple sclerosis, spina bifida, medullary traumatism, Creutzfeldt-Jakob disease). Medication regimen including estrogens, anti-estrogens or diuretics where dose and/or frequency has not been stable for at least the past 12 weeks or is anticipated to change during the course of the study. Chronic use of defined drugs and not stopped prior to inclusion into or including the study. Selective serotonin and norepinephrine reuptake inhibitor antidepressant (SSNRI), alpha-receptor antagonists/agonists, beta-3-receptor agonists or anticholinergic/-muscarinic drugs. Have any clinically significant coexisting condition or symptoms that, in the opinion of the investigator, would put the safety of the participant at risk. Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results. Medication known to affect lower urinary tract function. Patients having any electrical device inside their body (such as a cochlear implant, TENS stimulator (for pain), vagal nerve stimulator, brain stimulator, gastric pacemaker, bladder stimulator, or an implanted mechanical pump (such an insulin pump or pain pump). Patients having a cardiac pacemaker or defibrillator implant. Patients with Starr-Edwards artificial heart valve. Patients that suffer from claustrophobia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Low dose and High dose evaluation
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Already human tested low dose from phase I study | Biological: autologous muscle precursor cells<br>* Patients own Muscle Precursor Cells are isolated and injected into the rhabdomyosphincter<br>|
| Experimental: High dose<br>First in human dose used for efficacy reasons during phase II | Biological: autologous muscle precursor cells<br>* Patients own Muscle Precursor Cells are isolated and injected into the rhabdomyosphincter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of SUI episode frequency | Assessment in episode change measured using a bladder diary, from baseline to 6 months after injection. | 8-9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of (S)AEs | AEs related to obtaining biopsy, injection procedure and MPCs, including surgical injury, scars, urinary tract infection, inflammation, pelvic pain, prolonged urinary retention, voiding dysfunction, de novo urge incontinence, haematuria, aberrant tissue formation. Measured from Visit 2 (biopsy) to End of Study. | 6-8 months | 
| Number of patients with any clinical significant findings | Number of patients with any clinically significant findings based on physical examination, standard haematology, clinical chemistry and urinalysis profiles, blood pressure (BP), pulse and adverse events recordings at baseline, 1 month, 3 months and 6 months post-implantation. | 8-9 months | 
| Change in 24 hour pad weight | Change in pad weight based on using regular pad tests, from baseline to 6 months after injection. | 8-9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SUI, Incontinence, rhabdomyosphincter, urine, Stress Incontinence, LUTS, lower urinary tract