A Phase IIb, Multicenter, Double-Blind, Placebo-Controlled Induction Study with an Active Treatment Extension to Assess the Efficacy, Safety, and Pharmacokinetics of RO7837195 in Patients with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to evaluate the efficacy of RO7837195 compared with placebo in inducing remission in patients with moderately to severely active ulcerative colitis. Achievement of remission represents a clinically meaningful endpoint in ulcerative colitis management, reflecting control of inflammatory activity and improvement in disease manifestations.

The secondary objectives include:

• To evaluate the efficacy of RO7837195 compared with placebo in inducing response
• To evaluate the safety of RO7837195 compared with placebo
• To characterize the pharmacokinetics of RO7837195
• To evaluate the immunogenicity of RO7837195

This clinical trial enrolled a total of **140 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population included both **male and female subjects** from **adult and elderly age groups**. Participants were selected based on established diagnostic criteria, requiring a confirmed diagnosis of ulcerative colitis at least 3 months prior to screening with clinical and endoscopic evidence. The disease had to extend a minimum of 15 cm from the anal verge as determined by baseline endoscopy. Eligible participants presented with moderately to severely active disease, defined as a modified Mayo Score of 5-9 including an endoscopic subscore of at least 2 during the screening period. The trial population consisted of **patients** who had experienced prior advanced therapy failure and/or conventional therapy failure. Participants were required to have undergone colonoscopy within 2 years prior to screening or be willing to undergo the procedure at screening. The study included a **vulnerable population**. All participants were required to agree to adhere to specified contraception requirements throughout the trial.

This is a Phase IIb, multicenter, double-blind, placebo-controlled study with an active treatment extension designed to evaluate the efficacy, safety, and pharmacokinetics of **RO7837195** in patients with moderately to severely active **ulcerative colitis**. The investigational medicinal product RO7837195 is a **recombinant bispecific antibody** formulated as a **solution for injection** administered via **subcutaneous use**. The study employs a randomized, controlled design comparing RO7837195 with **placebo** during the induction phase, followed by an active treatment extension period. The trial is expected to commence recruitment in October 2025 and conclude in June 2028, with an estimated overall duration of approximately 32 months.

The primary objective is to evaluate the efficacy of RO7837195 compared with placebo in inducing remission in patients with moderately to severely active ulcerative colitis. The **primary endpoint** is defined as clinical remission at Week 12, characterized by a **modified Mayo Score** of ≤2, with specific Mayo subscores meeting the following criteria: stool frequency subscore ≤1, **rectal bleeding subscore** equal to 0, and endoscopy subscore ≤1 with the score of 1 modified to exclude friability. Secondary endpoints include clinical response at Week 12, defined as a decrease from baseline in the modified Mayo Score of ≥2 and ≥30% reduction from baseline, combined with a decrease in Mayo rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore of ≤1. Additional secondary endpoints encompass **endoscopic improvement** at Week 12, defined as a Mayo endoscopy subscore of ≤1, and **endoscopic remission** at Week 12, defined as a Mayo endoscopy subscore of 0.

Safety assessments constitute critical secondary endpoints and include the incidence and severity of **adverse events**, with severity determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 5.0. Changes from baseline in selected vital signs and clinical laboratory test results will be monitored throughout the study. Pharmacokinetic evaluations will measure serum concentration of RO7837195 at specified timepoints, while immunogenicity assessments will determine the prevalence of **anti-drug antibodies** at baseline and the incidence of anti-drug antibodies during the study period.

Eligible participants must have a diagnosis of ulcerative colitis established at least 3 months prior to screening, confirmed by clinical and endoscopic evidence during the screening period. Evidence of ulcerative colitis extending a minimum of 15 cm from the anal verge as determined by baseline endoscopy, either flexible **sigmoidoscopy** or **colonoscopy**, performed during screening is required. Participants must have undergone colonoscopy within 2 years prior to screening or demonstrate willingness to undergo colonoscopy in lieu of flexible sigmoidoscopy at screening. Disease activity must be moderately to severely active, defined as a modified Mayo Score of 5-9 including an **endoscopic subscore** of ≥2 during the screening period. Participants must have documented prior advanced therapy failure and/or conventional therapy failure. Agreement to adhere to contraception requirements is mandatory for eligible participants.

The study involves a structured sequence of visits beginning with a screening visit to assess eligibility criteria and establish baseline disease characteristics through endoscopic evaluation and clinical assessments. Following enrollment, participants will undergo randomization to receive either RO7837195 or placebo during the induction phase. Regular follow-up visits are scheduled to monitor efficacy through clinical and endoscopic assessments, evaluate safety parameters, collect pharmacokinetic samples, and assess immunogenicity. The primary efficacy assessment occurs at Week 12, corresponding to the conclusion of the induction phase. Participants completing the induction phase may be eligible to enter the active treatment extension period, during which continued monitoring of efficacy, safety, and pharmacokinetic parameters will occur. An end-of-study visit will be conducted to perform final safety and efficacy assessments. The expected length of participant involvement extends from the screening period through the completion of the active treatment extension and final follow-up assessments. Conditions that may lead to early termination from the study include withdrawal of consent, unacceptable adverse events, protocol violations, lack of efficacy, investigator decision, or administrative reasons as specified in the study protocol.

The experimental treatment under investigation in this clinical trial is **RO7837195**, a **recombinant bispecific antibody**. This investigational medicinal product is manufactured by GENENTECH, INC. and is identified by the sponsor product code RO 783-7195/F01-01. The active substance, RO7837195, is of protein origin and has been previously referred to by the synonym PF-07261271. The medicinal product is formulated as a **solution for injection** and is administered via the **subcutaneous route**. The study protocol designates RO7837195 as the test product in this **double-blind, placebo-controlled** investigation evaluating its efficacy, safety, and **pharmacokinetics** in patients with moderately to severely active **ulcerative colitis**. The study design includes an **induction phase** followed by an active treatment extension period, with a maximum treatment period specified as one day unit in the protocol documentation.

A **placebo** comparator is utilized in this trial to assess the efficacy of RO7837195. The placebo serves as the control treatment during the induction phase of the study, allowing for comparison against the experimental intervention. This comparator is administered in a manner consistent with the blinded study design to maintain the integrity of the efficacy evaluation. The primary objective of the trial is to evaluate the efficacy of RO7837195 compared with placebo in inducing **remission** in the target patient population.

The primary efficacy endpoint will be assessed at Week 12 and is defined as **clinical remission**, determined by a modified Mayo Score (mMS) of ≤ 2, with Mayo subscores meeting the following criteria: stool frequency subscore ≤ 1, rectal bleeding subscore = 0, and endoscopy subscore ≤ 1 (score of 1 modified to exclude friability).

Secondary efficacy endpoints will also be evaluated at Week 12 and include **clinical response**, defined as a decrease from baseline in the mMS of ≥ 2 and ≥ 30% reduction from baseline, combined with a decrease in Mayo rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. Additional secondary endpoints comprise **endoscopic improvement**, defined as a Mayo endoscopy subscore of ≤ 1 (score of 1 modified to exclude friability), and **endoscopic remission**, defined as a Mayo endoscopy subscore of 0. Safety assessments will include the incidence and severity of adverse events, determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) grading scale, as well as changes from baseline in selected vital signs and clinical laboratory test results. Pharmacokinetic parameters will be evaluated through serum concentration of RO7837195 at specified timepoints. Immunogenicity will be assessed by determining the prevalence of anti-drug antibodies (ADAs) at baseline and the incidence of ADAs during the study.