Efficacy and Safety of RO7790121 in Induction and Maintenance Therapy for Moderately to Severely Active Ulcerative Colitis: A Phase III, Multicenter, Double-Blind Study

The primary objective of this study is to evaluate the **efficacy** of RO7790121 compared with placebo in inducing and maintaining clinical remission in patients with moderately to severely active **ulcerative colitis**. This is clinically relevant as achieving and sustaining remission is a critical goal in the management of ulcerative colitis, aiming to improve patient outcomes and quality of life.

Secondary objectives include: - Evaluating the efficacy of RO7790121 compared with placebo in inducing response. - Assessing the efficacy in maintaining response. - Evaluating efficacy in biomarker-defined subpopulations of participants. - Assessing efficacy in terms of UC-related symptoms and health-related quality of life. - Evaluating efficacy in terms of the participant's global impressions. - Evaluating the safety of RO7790121 compared with placebo.

The clinical trial involves a total of **59 participants** diagnosed with **Moderately to Severely Active Ulcerative Colitis (UC)**. The study population includes both male and female subjects, aged between **18 to 80 years**, with a body weight of at least 40 kg. Participants were selected based on a confirmed diagnosis of UC, with active disease verified through endoscopy. The trial includes individuals who have shown an inadequate response, loss of response, or intolerance to prior conventional therapies such as aminosalicylates, corticosteroids, and immunosuppressants, while being naïve to advanced therapies like biologics or targeted small molecules. Screening for colorectal cancer is mandatory for all participants. The trial population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive evaluation of the investigational treatment's efficacy in inducing and maintaining clinical remission in UC patients.

The clinical trial is a **Phase III**, multicenter, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of induction and maintenance therapy with RO7790121 in patients with moderately to severely active **ulcerative colitis**. The trial aims to compare RO7790121 with a placebo in inducing and maintaining clinical remission. The study is expected to commence recruitment on October 31, 2024, and conclude by December 31, 2029. Participants will be randomly assigned to receive either the investigational product or a placebo, ensuring the study's double-blind nature, where neither the participants nor the investigators will know the treatment assignments.

The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis of ulcerative colitis, and previous treatment history. Participants must be between 18 to 80 years old, with a body weight of at least 40 kg, and must have an inadequate response or intolerance to prior conventional or advanced therapies. Following the screening, eligible participants will undergo baseline assessments before randomization. Subsequent follow-up visits will occur at regular intervals to monitor the participants' response to treatment, assess safety, and collect data on primary and secondary endpoints, including clinical remission and endoscopic improvement at specified weeks.

The primary endpoint is achieving clinical remission, defined by a modified Mayo Score (mMS) of ≤2, with specific subscores, at Week 12 and Week 52. Secondary endpoints include various measures of clinical response, endoscopic and histologic improvements, and patient-reported outcomes. The expected duration of participant involvement is approximately 52 weeks, with conditions for early termination including adverse events, withdrawal of consent, or failure to adhere to the study protocol. The trial will also monitor the incidence and severity of adverse events, ensuring participant safety throughout the study duration.

The clinical trial involves the evaluation of **RO7790121**, an experimental medication developed by F. Hoffmann-La Roche Ltd. This investigational product is characterized as a **protein** of other origin, indicating its classification within the broader category of protein-based therapeutics. The pharmaceutical form, dosage, route, and frequency of administration for RO7790121 are not specified in the available data. The primary objective of the trial is to assess the efficacy and safety of RO7790121 in inducing and maintaining clinical remission in patients with moderately to severely active **ulcerative colitis**. The trial is designed as a Phase III, multicenter, double-blind, placebo-controlled study, ensuring rigorous evaluation of the investigational product's therapeutic potential.

In addition to the experimental treatment, the study includes a **placebo** as a comparator treatment. The placebo is utilized to provide a control group for evaluating the true efficacy of RO7790121, ensuring that any observed effects can be attributed to the investigational product rather than external factors. The placebo is administered in a manner consistent with the experimental treatment to maintain the study's double-blind design. Details regarding the pharmaceutical form, dosage, and administration of the placebo are not provided in the available data.

The efficacy of the investigational product RO7790121 in the treatment of moderately to severely active **ulcerative colitis** will be assessed through a series of primary and secondary endpoints. The primary endpoint is clinical remission, defined as a modified Mayo Score (mMS) of ≤ 2, with a stool frequency subscore (SFS) of 0 or 1, rectal bleeding subscore (RBS) of 0, and endoscopic subscore (ES) of 0 or 1, evaluated at Week 12 and Week 52.

Secondary endpoints include a range of clinical, endoscopic, and histologic measures. These include partial modified Mayo Score (pmMS) from baseline to Week 2, endoscopic improvement and remission at Week 12, and clinical response at Week 12. Histologic assessments will be conducted using the Geboes score, with improvement defined as ≤ 3.1 and remission as < 2B, both at Week 12. Additional endpoints include histologic-endoscopic mucosal improvement and remission, maintenance of remission, corticosteroid-free remission, and various patient-reported outcomes such as bowel urgency, abdominal pain, fatigue (measured by FACIT-F), and overall change in UC symptoms (measured by PGIC and PGIS) from baseline to Week 52.

Data collection will occur at specified timepoints, including baseline, Week 2, Week 12, and Week 52, using validated scales and instruments. The analysis will focus on both the overall population and biomarker-defined subgroups, with specific attention to clinical remission and endoscopic improvement at Weeks 12 and 52. The incidence and severity of adverse events, including serious adverse events and those leading to study treatment discontinuation, will also be monitored throughout the trial.