Evaluation of Autologous Adipose-Derived Mesenchymal Stem Cells for Urinary Incontinence Post-Radical Prostatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this clinical trial is to evaluate the **urinary incontinence** in the pad test and assess the safety of the Advanced Therapy Medicinal Product (ATIMP) after injection within the urethral sphincter complex, compared to a placebo. This is clinically relevant as it aims to determine the efficacy and safety of a novel somatic cell-based therapy for patients experiencing urinary incontinence following radical prostatectomy, a common complication that significantly impacts quality of life.

Secondary objectives include the evaluation of the therapeutic effectiveness of the product after injection within the urethral sphincter compared to a placebo. This will provide additional insights into the potential benefits of the therapy in managing urinary incontinence.

The clinical trial focuses on **urinary incontinence** and involves a study population exclusively composed of male participants. The age range of the participants is adults over 18 years, specifically those who have undergone robot-assisted radical prostatectomy. The trial does not include a vulnerable population. Participants are required to have a **Body Mass Index (BMI)** greater than 20 kg/m², with adipose tissue in the abdominal cavity and buttocks eligible for liposuction. The study excludes individuals with positive results for HIV, hepatitis B, hepatitis C, and syphilis, as these are criteria related to the production of the ATIMP product. The sponsor has not provided information regarding the total number of participants. The selection criteria include males with Grade 2 stress urinary incontinence, confirmed by a 24-hour pad test and a urodynamic study, and a postoperative prostate cancer stage of pT2c N0 M0 with specific Gleason scores. The trial population was selected based on these specific health conditions and lifestyle considerations, ensuring a targeted approach to evaluating the safety and efficacy of the investigational product.

The clinical trial is designed to evaluate the effectiveness and safety of a **somatic cell-based therapy** for **urinary incontinence** in patients who have undergone radical prostatectomy. This is a multicenter, randomized, double-blind, placebo-controlled trial. The trial is expected to commence recruitment on May 1, 2024, and conclude by January 31, 2028. Participants will be randomly assigned to receive either the investigational product, which consists of **autologous adipose-derived mesenchymal stem cells in vitro expanded**, or a placebo. The primary objective is to assess the reduction in pad weight in a 24-hour pad test and the safety of the product when injected into the urethral sphincter complex.

The trial will include several study visits, beginning with a screening visit to determine eligibility based on specific inclusion criteria, such as being male, over 18 years old, and having Grade 2 stress urinary incontinence. Participants must also have a confirmed diagnosis of stress urinary incontinence through a urodynamic study and meet other health criteria. Following the screening, eligible participants will undergo baseline assessments before randomization. Subsequent visits will involve the administration of the investigational product or placebo, followed by regular follow-up visits to monitor efficacy and safety outcomes. The end-of-study visit will conclude the participant's involvement, which is expected to last until the trial's completion in 2028.

Participants may be withdrawn from the study if they experience serious adverse events or if they no longer meet the study criteria. The primary endpoints include the percentage of patients achieving a 50% reduction in pad weight and the frequency of serious adverse events. Secondary endpoints focus on improvements in sphincter contractility, bladder parameters, and lower urinary tract symptoms. The trial is categorized as a Phase I/II clinical trial, indicating an early stage of testing in humans to evaluate safety and preliminary efficacy.

The clinical trial involves the use of two primary treatments. The first treatment is **Natrium chloratum 0.9% Kabi**, a solvent for parenteral use, containing **sodium chloride** as the active substance. This product is manufactured by Fresenius Kabi Polska Sp. z o.o. and is authorized under the marketing authorization number 16039. The pharmaceutical form is a solvent for parenteral use, and it is administered via application. The sodium chloride solution is used as a diluting agent and is classified under the ATC code V07AB. The product is not a pediatric formulation and does not have orphan drug status.

The second treatment is the **Stress Urinary Incontinence Cellular Therapy**, which is a suspension for injection containing **autologous adipose-derived mesenchymal stem cells in vitro expanded**. This advanced therapy medicinal product (ATMP) is developed by Nicolaus Copernicus University and is identified by the sponsor product code SUICell. The therapy is administered via intramuscular injection into the urethral sphincter complex. The product is designed to evaluate the effectiveness and safety of somatic cell-based therapy for urinary incontinence in patients post-radical prostatectomy. The product is not a pediatric formulation and does not have orphan drug status. The trial is a multicenter, randomized, double-blind, placebo-controlled study.

The efficacy of the investigational treatment for **stress urinary incontinence** will be assessed using both primary and secondary endpoints. The primary endpoints include the percentage of patients who achieve a 50% reduction in pad weight in a 24-hour pad test after the injection of the Advanced Therapy Medicinal Product (ATIMP) within the urethral sphincter, compared to a placebo. Additionally, the early and long-term frequency of Serious Adverse Events (SAEs) following the ATIMP injection will be evaluated.

Secondary endpoints will focus on the percentage of patients achieving visible sphincter contractility as observed through flexible ureteroscopy. Improvements in bladder parameters and urinary continence will be measured using urodynamic tests, specifically cystometry and uroflowmetry. Furthermore, the percentage of patients experiencing an improvement in lower urinary tract symptoms (LUTS) will be assessed using the International Prostate Symptom Score (IPSS) scale, with a minimum 20% reduction in LUTS symptoms being considered significant.