Evaluation of Escherichia coli Strain Nissle 1917 in the Management of Autoimmune Non-Infectious Uveitis: A 12-Month Follow-Up Study

The primary objective of this study is to evaluate the **efficacy** of **Escherichia coli Nissle 1917** (ECN) in patients with **non-infectious uveitis**. This is clinically relevant as it aims to determine the potential therapeutic benefits of ECN, a probiotic, in managing this inflammatory eye condition, which can lead to vision impairment if not effectively treated.

Secondary objectives include:

• Assessing changes in best-corrected visual acuity (BCVA), which is crucial for understanding the impact of treatment on visual function.
• Evaluating uveitis activity using the Standardization of Uveitis Nomenclature (SUN) criteria, providing a standardized measure of disease activity.
• Assessing changes in optical coherence tomography (OCT) parameters, offering insights into structural changes in the retina.
• Verifying the safety and tolerability of ECN, ensuring that the treatment is not only effective but also safe for patient use.

The clinical trial focuses on evaluating the efficacy of **Escherichia coli Nissle 1917 (ECN)** in patients diagnosed with **non-infectious uveitis**. The study population comprises adults aged 18 to 64 years, inclusive of both male and female participants. The trial does not involve a vulnerable population. Participants were selected based on their medical history of autoimmune anterior, intermediate, posterior, or pan-uveitis, with a requirement of having experienced a flare-up within six months prior to the baseline visit. The sponsor has not provided information regarding the total number of participants. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed to evaluate the efficacy of **Escherichia coli** Nissle 1917 (ECN) in patients with autoimmune uveitis. This is a Phase 4, randomized, double-blind, controlled study with a duration of 12 months. The trial aims to assess the time to first disease relapse from the baseline visit, with secondary endpoints including the severity of the first relapse according to the SUN system, the total number of relapses during the study, and changes in BCVA and OCT parameters. Participants will be adults aged 18 to 64 years with autoimmune anterior, intermediate, posterior, or pan-uveitis who have experienced a flare-up within six months prior to the baseline visit.

The study will commence with an inclusion (screening) visit to determine eligibility based on the principal inclusion criteria. Following successful screening, participants will be randomized to receive either the investigational product, Mutaflor, containing **Escherichia coli** strain Nissle 1917, or a placebo. The investigational product is administered orally in the form of gastro-resistant capsules, with a maximum daily dose of 4 billion CFU. Study visits will occur at regular intervals throughout the 12-month period to monitor efficacy and safety outcomes. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participant involvement is expected to last for the entire 12-month duration of the study, barring any conditions that may necessitate early termination. Such conditions include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The study is conducted under the regulatory framework of Regulation (EU) No 536/2014, ensuring compliance with current clinical trial standards. The trial is not classified as a low-intervention study, and it is essential to maintain the integrity of the double-blind design to ensure unbiased results.

The clinical trial involves the administration of the experimental medication **Mutaflor**, which contains the active substance **Escherichia coli strain Nissle 1917**. This medication is provided in the form of a **gastro-resistant capsule, hard**, ensuring the active substance is delivered effectively to the gastrointestinal tract. The dosage is specified as 4 billion CFU (colony forming units) per day, with the route of administration being oral. The maximum treatment period for this study is 12 months, during which participants will receive the medication daily. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The focus remains solely on evaluating the efficacy of the probiotic supplementation with **Escherichia coli strain Nissle 1917** in subjects diagnosed with autoimmune uveitis. The trial aims to assess the therapeutic potential of this probiotic strain over the specified duration, with careful monitoring of participant responses and any adverse effects.

The efficacy of Escherichia coli Nissle 1917 (ECN) in patients with autoimmune uveitis will be assessed through a series of predefined endpoints. The primary endpoint is the time to first disease relapse from the baseline visit (V2). Secondary endpoints include the severity of the first relapse according to the Standardization of Uveitis Nomenclature (SUN) system, the total number of relapses during the study, changes in Best Corrected Visual Acuity (BCVA), and changes in Optical Coherence Tomography (OCT) parameters.

Data collection will occur over a 12-month follow-up period, with specific timepoints for assessment not explicitly detailed. The study will utilize validated scales and clinical measures to evaluate these endpoints, ensuring a robust analysis of the probiotic's impact on disease progression and symptomatology. The trial is designed to provide comprehensive insights into the therapeutic potential of ECN in managing autoimmune uveitis, with a focus on both the frequency and severity of disease relapses.