Phase IIa Randomized Controlled Trial Evaluating Efficacy, Safety, and Dosage of MBK-01 and Drug Combination in Recurrent Diverticulitis Treatment

The primary objective of this Phase IIa clinical trial is to evaluate the **efficacy** of the investigational medicinal product MBK-01, which consists of Full Spectrum & Purified Intestinal Microbiota oral capsules, in reducing the frequency of acute episodes in patients with **recurring diverticulitis**. Additionally, the trial aims to assess the safety and tolerability of MBK-01 across different treatment regimens and to determine the optimal dosing regimen. These objectives are clinically relevant as they address the need for effective and safe treatment options for patients suffering from recurrent episodes of diverticulitis, a condition that can significantly impact quality of life and lead to complications if not managed properly.

The secondary objective is to assess the effect of capsule-based Fecal Microbiota Transplantation (FMT) on patient-perceived health outcomes. This evaluation is important for understanding the broader impact of the treatment on patients' overall health and well-being, beyond the reduction of acute episodes.

The clinical trial focuses on evaluating the efficacy and safety of MBK-01 in patients with **recurring diverticulitis**. The study population includes both male and female participants aged between 18 and 70 years. Participants are required to have experienced three or more episodes of acute diverticulitis of the left or sigmoid colon within the three years prior to enrollment, with each episode confirmed through imaging tests. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria emphasize the inclusion of individuals who have not had any symptomatic episodes of acute diverticulitis in the 30 days preceding the trial. Additionally, participants of reproductive age must adhere to contraceptive measures throughout the study duration. The trial population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive assessment of the treatment's impact across different demographic groups.

The clinical trial is designed as a **randomized**, controlled, open-label study to evaluate the efficacy, safety, and tolerability of the investigational medicinal product MBK-01, which consists of lyophilized capsules of **fecal microbiota**. The trial aims to determine the optimal dosage for treating patients with **recurring diverticulitis**. The study will involve participants aged 18 to 70 years who have experienced three or more episodes of acute diverticulitis in the past three years, confirmed by imaging tests. The trial is expected to commence recruitment on December 31, 2023, and conclude by December 31, 2025.

Participants will be randomly assigned to receive either the investigational product or a control treatment. The investigational product, MBK-01, will be administered orally, with a maximum daily dose of 1 gram and a total treatment period of 17 days. The control treatments include **metronidazole**, **fosfomycin**, and **amoxicillin**, each with a maximum treatment period of 3 days. The primary endpoints include the number of new episodes of acute diverticulitis and the occurrence of adverse events during the trial. Secondary endpoints focus on the time to first and successive episodes of diverticulitis, hospitalizations, and changes in quality of life indices.

The trial will consist of several study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Participants will then undergo baseline assessments before starting the treatment regimen. Follow-up visits will be scheduled to monitor the participants' health, assess the occurrence of diverticulitis episodes, and evaluate any adverse events. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted to gather data on the primary and secondary endpoints.

Participant involvement is expected to last for the duration of the treatment period plus any additional follow-up required to assess outcomes. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the investigators. The trial is structured to ensure rigorous data collection and analysis, contributing to the understanding of the efficacy and safety of MBK-01 in managing recurring diverticulitis.

The clinical trial involves the administration of **lyophilized capsules of fecal microbiota**, designated as MBK-01, which is the investigational medicinal product. These capsules contain **allogeneic faecal microbiota, pooled** and are provided in a capsule form for **oral use**. The maximum daily dose is 1 gram, with a total maximum dose of 10 grams over a treatment period of 17 days. The primary objective is to evaluate the efficacy, safety, and tolerability of MBK-01 in patients with recurrent diverticulitis, as well as to determine the optimal dosing regimen.

In addition to the experimental treatment, the study includes the use of **metronidazole**, a chemical-origin medication, as a comparator treatment. Metronidazole is administered orally, with a maximum daily dose of 750 milligrams and a total maximum dose of 2250 milligrams over a 3-day treatment period. This medication is used to provide a standard-of-care comparison for the investigational product.

Another non-experimental treatment used in the study is **fosfomycin**, also of chemical origin. Fosfomycin is administered orally, with a maximum daily dose of 3000 milligrams and a total maximum dose of 9000 milligrams over a 3-day treatment period. This treatment serves as an additional comparator to assess the efficacy of the investigational product.

Lastly, **amoxicillin** is included as a non-experimental treatment. This chemical-origin medication is administered orally, with a maximum daily dose of 1500 milligrams and a total maximum dose of 4500 milligrams over a 3-day treatment period. Amoxicillin is used to further evaluate the investigational product's performance against standard treatments.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed regimens. The trial aims to provide comprehensive data on the investigational product's effectiveness in reducing the frequency of acute diverticulitis episodes compared to these standard treatments.

The efficacy of the investigational medicinal product MBK-01, consisting of lyophilized capsules of **allogeneic faecal microbiota**, will be assessed in a Phase IIa randomized, controlled, open-label clinical trial. The primary endpoints for evaluating efficacy include the number of new episodes of acute diverticulitis during the trial and the occurrence of treatment-related adverse events between the two MBK-01 regimens. Secondary endpoints will focus on the time to the first and successive episodes of acute diverticulitis, the number of hospitalizations due to acute diverticulitis, the number of courses of systemic antibiotic treatments used, the need for surgery, and changes in the Gastrointestinal Quality of Life Index (GIQLI) and SF-36 questionnaires.

Data collection will occur at specified intervals throughout the trial, with efficacy parameters being measured and analyzed using validated scales and questionnaires. The trial aims to determine the optimal dosing regimen for MBK-01 by comparing its efficacy and safety against a control group in reducing the frequency of acute diverticulitis episodes. The trial is designed to provide comprehensive insights into the efficacy of MBK-01 in patients with recurrent diverticulitis, contributing to the understanding of its potential therapeutic benefits.