SUISSE MPC2: Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy

Sponsor

University of Zurich (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05534269

Collaborator

GCP-Service International Ltd. & Co. KG (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Female Stress Urinary Incontinence	Biological: autologous muscle precursor cells	Phase 2

Detailed Description

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 patients 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 obtaing a muscle biopsy up to 8 weeks later, an injection of MPCs up to 5 weeks later, and follow-up visits after 1, 3 and 6 months post injection.

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 independend Data Safety Monitoring Board consisting of independent physicians and experts in the field. The injection is performed with ultrasound guidence using an endocavity ultrasound probe.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Low dose and High dose evaluationLow dose and High dose evaluation

Masking:

Single (Participant)

Masking Description:

Neither patient nor sponsor will know which patient gets which dose

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Low dose

Already human tested low dose from phase I study

Biological: autologous muscle precursor cells

Patients own Muscle Precursor Cells are isolated and injected into the rhabdomyosphincter

Experimental: High dose

First in human dose used for efficacy reasons during phase II

Biological: autologous muscle precursor cells

Patients own Muscle Precursor Cells are isolated and injected into the rhabdomyosphincter

Outcome Measures

Primary Outcome Measures

Change of SUI episode frequency [8-9 months]
Assesment in episode change measured using a bladder diary, from baseline to 6 months after injection.

Secondary Outcome Measures

Incidence of (S)AEs [6-8 months]
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.
Number of patients with any clinical significant findings [8-9 months]
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.
Change in pad weight [8-9 months]
Change in pad weight based on using regular pad tests, from baseline to 6 months after injection.

Other Outcome Measures

Change in total leakage episodes [8-9 months]
Response rate at 6 months, defined as percentage of patients with at least 50% change in number of stress leaks
Questionnaire ICIQ-UI SF (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form ) [8-9 months]
Change in score from baseline to 6 months. Containing 1 scale ranging from 0 (not at all) to 10 (serious) measuring the impairment caused by urine leakage in everyday life.
Questionnaire ICIQLUTSqol (International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms quality of Life) [8-9 months]
Change in score from baseline to 6 months. This questionnaire contains 21 questions to measure the impact of urinary incontinence on quality of life with particular reference to social effects. Each question is accompanied by a scale to capture the subjective restriction concerning the respective topic. These scales range from 0 (not at all) to 10 (very much).
Questionnaire VAS (Visual analogue scale) [8-9 months]
Change score for degree of suffering, quality of life overall and subjective health status from baseline to 6 months. Scales ranging from 0 to 10. For Quality of life and health status from 0 "very bad" to 10 "very well". The degree of suffering from 0 (low) to 10 (high).
Urethral pressure profile [8-9 months]
It measures the changes in the bladder pressure (in cm/H2O) required to urinate and the flow rate (in ml/s) a given pressure generates between baseline and 6 months after injection.
Urodynamic cystometric test [8-9 months]
It measures the change of how much urine (in mL) the bladder can hold, between baseline and 6 months after injection.
Urodynamic cystometric test [8-9 months]
It measures the change how much pressure builds up inside the bladder (in cm/H2O) as it stores urine, between baseline and 6 months after injection.
Urodynamic cystometric test [8-9 months]
It measures the change how full the bladder is (in mL) when the urge to urinate occurs, between baseline and 6 months after injection.
Urodynamic leak point pressure measurement [8-9 months]
It measures the changes of pressure (in cm/H2O) at the point of leakage between baseline and 6 months after injection.
% of subjects with successful injection [1 day]
at day of implantation

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.