Evaluation of Rosnilimab Efficacy and Safety in Moderate to Severe Ulcerative Colitis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to assess the clinical efficacy of **rosnilimab** versus placebo in subjects with moderate to severe **ulcerative colitis** (UC). This evaluation is clinically relevant as it aims to determine the potential of rosnilimab to improve clinical outcomes in patients suffering from this chronic inflammatory bowel disease, which can significantly impact quality of life and may lead to serious complications if not effectively managed.

Secondary objectives include:

• Safety Objective: To evaluate the safety and tolerability of rosnilimab versus placebo in subjects with moderate to severe UC.
• Pharmacokinetic (PK) Objectives: To evaluate the PK of rosnilimab in subjects with moderate to severe UC.
• Pharmacodynamic (PD) Objectives: To evaluate the PD of rosnilimab in subjects with moderate to severe UC.
• Immunogenicity Objective: To evaluate the immunogenicity of rosnilimab in subjects with moderate to severe UC.

The clinical trial involves a total of **39 participants** diagnosed with **Ulcerative Colitis** (UC). The study population includes both male and female subjects aged 18 years and older, with a clinical diagnosis of moderate to severe active UC. Participants were selected based on their history of inadequate response, loss of response, or intolerance to at least two classes of UC therapies, such as aminosalicylates, corticosteroids, immunomodulators, calcineurin inhibitors, or advanced UC therapies. The trial population is characterized by individuals who have completed necessary eDiary entries and have undergone recent surveillance colonoscopy to rule out dysplasia or colon cancer. The study does not specify particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the participants have a documented history of UC, confirmed by biopsy results, and meet the defined clinical severity criteria.

The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Rosnilimab** in subjects with moderate to severe **ulcerative colitis**. The trial aims to assess the clinical efficacy of Rosnilimab compared to placebo, with the primary endpoint being the mean change from baseline in the modified Mayo Score (mMS) at Week 12. Secondary endpoints include the proportion of subjects achieving clinical remission, endoscopic improvement, and clinical response at Week 12, as well as exploratory endpoints assessed at Weeks 12, 24, and 50.

The trial is expected to commence recruitment on May 1, 2024, and conclude by September 29, 2026. Participants will be involved in the study for a maximum treatment period of 50 weeks. The study involves multiple visits, starting with a screening visit to confirm eligibility based on inclusion criteria such as age, clinical diagnosis of ulcerative colitis, and previous treatment history. Baseline assessments will be conducted prior to randomization. Participants will receive either Rosnilimab or a placebo administered subcutaneously as a solution for injection.

Follow-up visits will occur at regular intervals to monitor efficacy and safety outcomes, including vital signs, laboratory parameters, and adverse events. The end-of-study visit will evaluate the overall treatment response and collect final safety data. Participants may be withdrawn from the study if they experience severe adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study is not a low-intervention trial and is conducted under the sponsorship of ANAPTYSBIO, INC.

The clinical trial involves the administration of **Rosnilimab**, an investigational medication, to evaluate its efficacy and safety in subjects with moderate to severe **ulcerative colitis**. Rosnilimab is formulated as a **solution for injection** and is administered via the **subcutaneous** route. The active substance, Rosnilimab, is a protein of other origin, and the pharmaceutical form is specifically designed for injection. The dosing schedule and frequency of administration are determined by the study protocol, with a maximum treatment period of 50 days. The trial ensures that the administration of Rosnilimab is monitored for participant compliance, although specific dosing amounts are not disclosed in the provided data.

In addition to the experimental treatment, the study includes a **placebo** group to match the Rosnilimab solution for injection. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring the study remains double-blind. The placebo does not contain any active substance and serves as a comparator to assess the true efficacy of Rosnilimab. The administration of the placebo follows the same protocol as the experimental medication, maintaining consistency in the study design.

The clinical trial aims to evaluate the efficacy of **rosnilimab** in subjects with moderate to severe ulcerative colitis. Efficacy will be primarily assessed by measuring the mean change from baseline in the modified Mayo Score (mMS) at Week 12. Secondary efficacy endpoints include the proportion of subjects achieving clinical remission, defined as an mMS ≤ 2, with a stool frequency subscore (SFS) ≤ 1, rectal bleeding score (RBS) = 0, and endoscopic subscore ≤ 1 without friability, at Week 12. Additionally, the proportion of subjects showing endoscopic improvement, defined as an endoscopy subscore ≤ 1 without friability, and those achieving a clinical response, defined as a decrease from baseline in mMS ≥ 2 points and ≥ 30% with a decrease from baseline in RBS ≥ 1 point or an absolute RBS ≤ 1, will be evaluated at Week 12.

Exploratory efficacy endpoints will assess the proportion of subjects achieving endoscopic remission, defined as an endoscopy subscore = 0, and histologic-endoscopic mucosal improvement, defined as an endoscopic subscore of 0 and a Geboes score ≤ 2, at Weeks 12, 24, and 50. The mean change from baseline in various assessments, including mMS, partial mMS (pmMS), Inflammatory Bowel Disease Questionnaire (IBDQ), individual mMS subscores (RBS, SFS, and endoscopy subscore), and Geboes score, will also be explored at specified time points. These efficacy parameters will be collected and analyzed using validated scales and laboratory tests at designated intervals throughout the study duration.