Efficacy of OM-89 Versus Placebo in Reducing Antibiotic Use for Recurrent Urinary Tract Infections in Patients with Neurogenic Bladder: A Randomized Trial

The primary objective of this study is to compare the **incidence rate** of courses of antibiotics for **urinary tract infections** (UTIs) between month 0 (M0) and month 12 (M12) in patients with a spinal cord injury and a stabilized **neurogenic bladder** who are on clean intermittent catheterization (CIC). The comparison is between those receiving OM-89 (experimental group) and those receiving a placebo (control group). This objective is clinically relevant as it aims to evaluate the efficacy of OM-89 in reducing antibiotic consumption, which is crucial for managing recurrent UTIs and minimizing antibiotic resistance in this patient population.

Secondary objectives include:

• Comparing the incidence rate of febrile and non-febrile UTIs at M12 and M24, and the trend over two years.
• Assessing hospitalization rates for UTIs and sepsis with a urinary tract origin at M12 and M24, and changes over two years.
• Evaluating the number of days on antibiotics for urinary and any indications during the first and second years, considering all antibiotics and excluding those with low ecological impact.
• Comparing the number of courses of antibiotics for urinary and any indications at M12 and M24.
• Assessing the health-related quality of life of patients at multiple time points and its evolution over time.
• Evaluating the safety of long-term treatment with OM-89.

The clinical trial involves participants diagnosed with **recurrent urinary tract infections** and a stabilized **neurogenic bladder** following a spinal cord injury. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a stabilized neurogenic bladder for more than two years and must have undergone a urodynamic examination within the last two years. They are also required to use clean intermittent catheterization (CIC) five to six times per day. Additionally, participants must have received at least six courses of antibiotic treatment for urinary tract infections in the 12 months prior to screening. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of OM-89 compared to placebo in reducing antibiotic consumption associated with the treatment of **urinary tract infections** in patients with a **neurogenic bladder**. The trial will include a roll-over phase and is expected to last until October 2028, with recruitment starting in October 2024. Participants will be randomly assigned to receive either the experimental treatment, OM-89, or a placebo, both administered in the form of hard gelatin capsules. The primary objective is to compare the incidence rate of antibiotic courses for urinary tract infections between the baseline and 12 months in patients with a stabilized neurogenic bladder following spinal cord injury.

The study will involve several visits, beginning with a screening visit to confirm eligibility based on criteria such as age, medical history, and current health status. Participants must have a stabilized neurogenic bladder, use clean intermittent catheterization, and have a history of recurrent urinary tract infections. Following the screening, eligible participants will be enrolled and randomized into the study. The trial will include follow-up visits at regular intervals to monitor the number of symptomatic urinary tract infections, hospitalizations, and antibiotic usage. The end-of-study visit will occur at 24 months, where final assessments will be conducted, including a quality of life evaluation using the Qualiveen questionnaire.

Participant involvement is expected to last for up to 24 months, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study procedures. The primary endpoint is the number of antibiotic treatment episodes for urinary tract infections per person-days at risk during the first year. Secondary endpoints include the number of symptomatic infections, hospitalizations, and quality of life scores at various time points. The trial aims to provide valuable insights into the management of recurrent urinary tract infections in patients with neurogenic bladder, potentially reducing the need for antibiotics and improving patient outcomes.

The clinical trial involves the administration of **Uro-Vaxom 6 mg capsule**, which is the experimental medication. This pharmaceutical product is presented in the form of a hard capsule and contains the active substance **E. coli polysaccharide**. The medication is administered orally, with a maximum daily dose of 6 mg and a total maximum dose of 1400 mg over the course of the treatment. The maximum treatment period is 240 days. The active substance is classified under the ATC code J07AX, which corresponds to other bacterial vaccines. The product is manufactured by OMEDICAMED UNIPESSOAL LDA and is authorized in Portugal.

The study also includes a **placebo** treatment, referred to as URO-VAXOM CAPSULES PLACEBO. This placebo is formulated as hard gelatin capsules containing pregelatinized starch, magnesium stearate, and mannitol. The placebo is designed to match the experimental medication in appearance and administration route, ensuring the double-blind nature of the trial. The placebo capsules are administered orally, following the same dosing schedule as the experimental medication, to maintain consistency in the treatment regimen across all participants.

Efficacy in this clinical trial will be assessed by comparing the incidence rate of courses of antibiotics for urinary tract infections (UTIs) between the experimental group receiving OM-89 and the control group receiving placebo. The primary endpoint is the number of antibiotic treatment episodes for UTIs per person-days at risk during the first year. An episode of treatment is defined as a single prescription of a given antibiotic, regardless of its intended duration, whether curative or prophylactic. A day at risk is defined as a follow-up day without antibiotic treatment.

Secondary endpoints include the number of symptomatic UTIs, both febrile and non-febrile, at months 12 (M12) and 24 (M24), compared with M12. Additionally, the number of febrile UTIs, hospitalizations for UTIs, and hospital admissions for sepsis with a urinary tract origin will be evaluated at M12 and M24. The number of days spent on antibiotics, both for urinary indications and any indication, as well as those with a significant ecological impact, will also be assessed at these time points. The number of courses of antibiotics for urinary indications and for any indication will be compared at M12 and M24. Quality of life will be measured using the Qualiveen questionnaire at months 0 (M0), 6 (M6), 12 (M12), 18 (M18), and 24 (M24). The number of adverse events (AEs) and their relationship to OM-89 will be categorized by severity, ranging from Grade 1 mild AE to Grade 5 AE-related death.