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

• ClinicalTrials.gov Identifier: NCT05534269
• Recruitment Status: Recruiting
• First Posted: September 9, 2022
• Last Update Posted: November 9, 2022
• Sponsor: University of Zurich
• Collaborator: GCP-Service International Ltd. & Co. KG
• Information provided by (Responsible Party): University of Zurich

Tracking Information

• First Submitted Date: August 23, 2022
• First Posted Date: September 9, 2022
• Last Update Posted Date: November 9, 2022
• Actual Study Start Date: October 17, 2022
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2022)

Change of SUI episode frequency [ Time Frame: 8-9 months ]

Assesment in episode change measured using a bladder diary, from baseline to 6 months after injection.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 6, 2022)

• Incidence of (S)AEs [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 8-9 months ]
  Change in pad weight based on using regular pad tests, from baseline to 6 months after injection.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 6, 2022)

• Change in total leakage episodes [ Time Frame: 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 ) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 day ]
  at day of implantation

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy
• Official Title: Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy
• Brief Summary: The aim of the SUISSE MPC 2 study is to treat stress urinary incontinence in adult women.

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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Low dose and High dose evaluation

Masking: Single (Participant)
Masking Description:

Neither patient nor sponsor will know which patient gets which dose

Primary Purpose: Treatment

• Condition: Female Stress Urinary Incontinence

Intervention

Biological: autologous muscle precursor cells

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

Study Arms

• Experimental: Low dose
  Already human tested low dose from phase I study
  Intervention: Biological: autologous muscle precursor cells
• Experimental: High dose
  First in human dose used for efficacy reasons during phase II
  Intervention: Biological: autologous muscle precursor cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 6, 2022): 70
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2025
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Participant has to have a female rhabdomyosphincter and urinary tract, independent from self-representation of gender identity.

• Ages: 20 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Markus Veit; +41442551223; markus.veit@usz.ch

Contact: Florian Schmid, MD / PhD; +4144255440; florian.schmid@usz.ch

• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT05534269
• Other Study ID Numbers: SUISSE MPC2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Zurich
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Zurich
• Original Study Sponsor: Same as current
• Collaborators: GCP-Service International Ltd. & Co. KG

Investigators

• Principal Investigator: Florian Schmid, MD / PhD; University of Zurich

• PRS Account: University of Zurich
• Verification Date: November 2022