Efficacy and Safety Evaluation of RO7790121 Induction Therapy in Moderately to Severely Active Ulcerative Colitis: A Phase III Multicenter Double-Blind Placebo-Controlled Study

The primary objective of this Phase III, multicenter, double-blind, placebo-controlled study is to evaluate the **efficacy** of RO7790121 compared with placebo in inducing clinical remission in patients with moderately to severely active **ulcerative colitis**. This is clinically relevant as achieving clinical 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 biomarker-defined subpopulations of participants.
• Evaluating the efficacy in terms of UC-related symptoms and health-related quality of life.
• Assessing the efficacy in terms of the participant's global impressions.
• Evaluating the **safety** of RO7790121 compared with placebo.

The clinical trial involves a total of **132 participants** diagnosed with **Moderately to Severely Active Ulcerative Colitis (UC)**. The study population includes both male and female subjects, aged between 18 and 80 years, with a body weight of at least 40 kg. Participants were selected based on a confirmed active UC diagnosis and an inadequate response, loss of response, or intolerance to prior conventional or advanced therapies. All participants underwent screening for colorectal cancer according to local standards. The trial includes individuals who are naïve to advanced therapies such as biologics or targeted small molecules. The study population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive evaluation of the treatment's efficacy across different demographics. Lifestyle factors such as diet and physical activity were not specified by the sponsor.

The clinical trial is designed to evaluate the efficacy and safety of **RO7790121** as an induction therapy in patients with moderately to severely active **ulcerative colitis**. This is a Phase III, multicenter, double-blind, placebo-controlled study. Participants will be randomly assigned to receive either the investigational product or a placebo. The trial aims to induce clinical remission, with the primary endpoint being a modified Mayo Score of ≤2 at Week 12. Secondary endpoints include various measures of clinical response, endoscopic improvement, and histologic outcomes, assessed at different time points throughout the study.

The trial is expected to commence recruitment on October 31, 2024, and conclude by December 31, 2029. Participants will be involved in the study for approximately 12 weeks, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The study visits are structured as follows: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and a final end-of-study visit to assess the primary and secondary endpoints. Inclusion criteria require participants to be aged 18 to 80 years, with a confirmed diagnosis of active ulcerative colitis and an inadequate response to prior therapies. Exclusion criteria are not specified in the provided data.

The clinical trial involves the evaluation of the experimental medication **RO7790121**, developed by F. Hoffmann-La Roche Ltd. This investigational product is a protein-based substance, classified under the category "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration for RO7790121 are not specified in the provided data. The primary objective of the trial is to assess the efficacy of RO7790121 in inducing 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.

In addition to the experimental treatment, a placebo is utilized as a comparator in this study. The placebo is intended to serve as a control to evaluate the true efficacy of RO7790121. Details regarding the composition, form, and administration of the placebo are not provided in the available data. The study's design ensures that neither the participants nor the investigators are aware of the treatment assignments, maintaining the integrity of the double-blind methodology.

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

Secondary endpoints include a range of clinical, endoscopic, and patient-reported outcomes. These include the partial modified Mayo Score (pmMS) from baseline to Week 2, endoscopic improvement and remission at Week 12, and clinical response characterized by a decrease in mMS of at least 2 points and 30% from baseline, with specific changes in RBS. Histologic assessments will be conducted to evaluate improvement and remission using the Geboes score at Week 12. Additional assessments will focus on histologic-endoscopic mucosal improvement and remission, as well as clinical remission and endoscopic improvement among biomarker-defined subgroups at Week 12.

Patient-reported outcomes will be measured using tools such as the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Patient Global Impression of Change (PGIC) and Severity (PGIS) scales, with evaluations conducted from baseline through Week 12. 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.