Efficacy and Safety of RO7790121 in Induction and Maintenance Therapy for Moderately to Severely Active Crohn's Disease: A Phase III Multicenter Double-Blind Study

The primary objective of this study is to evaluate the **efficacy** of RO7790121 compared with placebo in maintaining response in patients with moderately to severely active Crohn's Disease. This is clinically relevant as maintaining response is crucial for improving long-term outcomes and quality of life in patients with this chronic inflammatory condition.

Secondary objectives include:

• Evaluating the efficacy of RO7790121 compared with placebo in inducing response.
• Assessing the efficacy in maintaining response with respect to endoscopic remission, symptomatic remission, corticosteroid-free clinical remission, maintenance of clinical remission, maintenance of endoscopic response, clinical remission and endoscopic remission, and ulcer-free endoscopy.
• Evaluating the efficacy in terms of Crohn's Disease-related symptoms and health-related quality of life.
• Assessing efficacy in tumor necrosis factor-like ligand 1A (TL1A) biomarker-defined subgroups.
• Evaluating the efficacy in inducing and/or maintaining response.
• Assessing efficacy in terms of the participant’s global impressions and general well-being.
• Evaluating the safety of RO7790121 compared with placebo.
• Assessing the persistence of fistulas in participants treated with RO7790121 compared to placebo.

The clinical trial involves a total of **256 participants** diagnosed with **Moderately to Severely Active Crohn's Disease (CD)**. The study population includes both male and female subjects, aged between **18 to 80 years**, with the possibility of including individuals aged **16 to <18 years** where local regulations permit. Participants are required to have a body weight of at least **40 kg**. The trial population was selected based on a confirmed diagnosis of Crohn's Disease, supported by clinical, endoscopic, and histopathological evidence. Participants must exhibit moderately to severely active disease, with specific criteria such as a centrally-read SES-CD of **≥ 6** (or **≥ 4** for isolated ileal disease) and a CDAI between **220 and 450**. The involvement of the ileum and/or colon is necessary, with at least four colonic segments traversable by an endoscope, or three segments for those who have undergone bowel resection. Up-to-date colorectal cancer screening is mandatory, including a surveillance colonoscopy at screening or within the two years prior to baseline for those with colonic disease lasting over ten years or with risk factors for bowel cancer. The trial includes a vulnerable population, ensuring comprehensive screening and adherence to local standards for participant safety.

The clinical trial is designed as a **Phase III**, multicenter, double-blind, placebo-controlled study to evaluate the efficacy and safety of induction and maintenance therapy with RO7790121 in patients with moderately to severely active **Crohn's Disease**. The trial aims to compare the efficacy of RO7790121 with a placebo in maintaining response, with primary endpoints including clinical remission and endoscopic response at Week 52. Secondary endpoints encompass a range of clinical and symptomatic measures assessed at Weeks 12 and 52, including symptomatic remission, endoscopic remission, and corticosteroid-free clinical remission.

Participants will be randomly assigned to receive either the investigational product or a placebo, ensuring the study's double-blind nature. The trial is expected to commence recruitment on March 1, 2025, and conclude by December 31, 2030. The study will involve multiple visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and confirmed diagnosis of Crohn's Disease. Participants must have a centrally-read SES-CD of ≥ 6 (or ≥ 4 for isolated ileal disease) and a CDAI between 220 and 450.

Following the screening, participants will undergo regular follow-up visits to monitor their response to the treatment and assess any adverse events. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including the occurrence of serious adverse events or withdrawal of consent. The trial's rigorous design and comprehensive endpoints aim to provide valuable insights into the treatment of moderately to severely active Crohn's Disease.

The clinical trial involves the evaluation of **RO7790121**, an investigational medication developed by F. Hoffmann-La Roche Ltd. This experimental drug is being assessed for its efficacy and safety in the treatment of patients with moderately to severely active **Crohn's Disease**. RO7790121 is characterized as a protein-based substance, specifically categorized under "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration for RO7790121 are not explicitly detailed in the provided data. However, it is implied that the drug is administered in a manner consistent with standard clinical trial practices for such investigational therapies.

In addition to the experimental treatment, the study employs a **placebo** as a comparator to evaluate the efficacy of RO7790121. The placebo is used in a double-blind manner, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby maintaining the integrity of the study results. The placebo is administered in a form and schedule that matches the experimental drug to ensure consistency in the trial design. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the outcomes of the treatment.

The efficacy of the investigational product RO7790121 in patients with moderately to severely active **Crohn's Disease** will be assessed through a series of primary and secondary endpoints. The primary endpoints include clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, and endoscopic response, characterized by a decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) from baseline by at least 50%, both evaluated at Week 52.

Secondary endpoints will be measured at various timepoints, including Week 12 and Week 52. These include clinical remission and endoscopic response at Week 12, symptomatic remission, endoscopic remission, ulcer-free endoscopy, and corticosteroid-free clinical remission at Week 52. Additional assessments will involve symptomatic response, overall change in Crohn's Disease symptoms using the Patient Global Impression of Change (PGIC), and overall severity of symptoms using the Patient Global Impression of Severity (PGIS). Patient-reported outcomes such as bowel urgency, fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), and the Inflammatory Bowel Disease Questionnaire (IBDQ) score will also be evaluated from baseline to Weeks 12 and 52.

The efficacy parameters will be collected and analyzed at specified intervals, with key assessments occurring at Weeks 12 and 52. The study will utilize validated scales and patient-reported outcomes to ensure accurate and reliable measurement of efficacy. The trial is designed to provide comprehensive data on the efficacy of RO7790121 in maintaining response in patients with Crohn's Disease, contributing to the understanding of its therapeutic potential.