Evaluation of Mesalazine for Colorectal Neoplasia Prevention in Lynch Syndrome: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate whether **mesalamine** (5-ASA) reduces the occurrence of any colorectal neoplasia, including both benign and malignant tumors, in patients with **Lynch syndrome**. This is assessed in comparison to a placebo, as detected by any colonoscopy until the end of treatment, which spans 24 months plus an additional 3 months, and at the end of the study. Lynch syndrome is a hereditary condition that significantly increases the risk of developing colorectal cancer. The clinical relevance of this study lies in its potential to provide a preventive strategy for colorectal cancer in individuals with Lynch syndrome, thereby reducing morbidity and mortality associated with this high-risk group.

The clinical trial involves participants diagnosed with **Lynch syndrome**, a condition that increases the risk of developing colorectal cancer. The study population includes both male and female subjects, aged over 30 years, with a focus on those who are tumor-free, including individuals who have had polyps removed endoscopically. Participants are carriers of a germline pathologic mutation on one of the MMR genes, such as MLH1, MSH2 (including EpCAM), and MSH6. Females of childbearing potential are required to use a highly efficient method of contraception or agree to abstain from heterosexual activity during the treatment period, and must have a negative pregnancy test at screening and randomization. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The trial population was selected based on specific genetic criteria and health status, ensuring that participants are not currently affected by tumors. The study does not provide detailed information on lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating a need for careful ethical considerations in the study design and execution.

The clinical trial is designed to evaluate the efficacy of **mesalazine** in reducing the occurrence of colorectal neoplasia in patients with Lynch syndrome. This study is a randomized, double-blind, placebo-controlled trial, conducted over a period of 24 months, with an additional 3 months for follow-up, culminating in an end-of-study visit. Participants will be randomly assigned to receive either the active drug, Pentasa Sachet 2 g depotgranulat, or a placebo designed to resemble the active drug. The trial aims to assess the primary endpoint of the occurrence of any colorectal neoplasia, both benign and malignant, as detected by colonoscopy.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as being tumor-free and carrying a germline pathologic mutation on one of the MMR genes. Participants must be over 30 years of age, with females of childbearing potential required to use effective contraception and have a negative pregnancy test. Following randomization, participants will attend regular follow-up visits to monitor safety and efficacy outcomes, with the final visit marking the end of the study period.

Participant involvement is expected to last approximately 27 months, including the follow-up period. Conditions that may lead to early termination from the study include the development of significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial will also explore secondary endpoints, such as the number of neoplasias per patient, tumor progression, and the influence of factors like age and sex on treatment effects. Safety data will be collected and compared between the treatment and placebo groups in an exploratory manner.

The clinical trial involves the administration of **Pentasa Sachet 2 g depotgranulat**, which contains the active substance **mesalazine**. This medication is formulated as **prolonged-release granules** and is intended for **oral use**. The dosage is set at 2 grams per day, with a maximum total dose of 1460 grams over the course of the study. The treatment period is defined as 24 months, with an additional 3-month follow-up period. The granules are designed to release the active ingredient gradually, ensuring a sustained therapeutic effect. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

In addition to the experimental medication, a **placebo** is used as a comparator in this study. The placebo is presented as **Pentasa PLACEBO Sachet 2g**, formulated to resemble the active drug product in appearance and granule form. This ensures blinding and maintains the integrity of the study design. The placebo does not contain any active pharmaceutical ingredients and is used to assess the efficacy of mesalazine in reducing the occurrence of colorectal neoplasia in patients with Lynch syndrome. The administration schedule for the placebo mirrors that of the active treatment, with the same frequency and duration, to facilitate a direct comparison between the two groups.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the occurrence of any colorectal neoplasia, including both benign and malignant tumors, in patients with Lynch syndrome. The secondary endpoints include the number of colorectal neoplasias per patient, tumor progression across four ordered stages, and the dependence of treatment effects on factors such as history of colorectal cancer, sex, and age (categorized as less than 45 years and 45 years or older). Safety data will also be described and compared between groups in an exploratory manner.

The trial aims to determine whether **mesalamine** (5-ASA) reduces the occurrence of colorectal neoplasia compared to placebo. Efficacy assessments will be conducted through colonoscopies performed until the end of the treatment period, which spans 24 months, with an additional follow-up period of 3 months. The analysis will focus on the detection of neoplasia during these colonoscopies, providing a comprehensive evaluation of the treatment's impact on colorectal cancer prevention in the study population.