A Study to Assess the Efficacy and Safety of Afimkibart (Also Known as RO7790121) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis

Phase 3Active Not RecruitingNCT06589986

Hoffmann-La Roche400 enrolled

Overview

This Phase III, multicenter, double-blind, placebo-controlled, treat-through study will evaluate the efficacy and safety of Afimkibart (RO7790121) compared with placebo in participants with moderately to severely active ulcerative colitis (UC).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

400

Conditions

Moderately to Severely Active Ulcerative Colitis

Interventions

AfimkibartDRUG

Afimkibart will be administered as IV infusion. Afimkibart will be administered as SC injection.

PlaceboDRUG

Placebo matching IV afimkibart. Placebo matching SC afimkibart.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Confirmed diagnosis of UC * Moderately to severely active UC assessed by mMS * Bodyweight \>= 40 kilogram (kg) * Up to date with colorectal cancer (CRC) screening performed according to local standards * Demonstrated inadequate response, loss of response and/or intolerance to at least one protocol-specified conventional or advanced UC therapy * Males and females of childbearing potential must meet protocol criteria for contraception requirements Exclusion Criteria: * Currently known complications of UC (e.g. fulminant colitis, toxic megacolon) * Current diagnosis of Crohn's disease (CD) or indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis * Presence of an ostomy or ileoanal pouch * Current diagnosis or suspicion of primary sclerosing cholangitis * Pregnancy or breastfeeding, or intention of becoming pregnant during the study * Past or current evidence of definite low-grade or high-grade colonic dysplasia or adenomas or neoplasia not completely removed * History of malignancy within 5 years, with the exception of malignancies adequately treated with resection for non-metastatic basal cell or squamous cell cancer or in situ cervical cancer * Evidence of infection with Clostridioides difficile (C. difficile; formerly known as Clostridium difficile), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV) * Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidance) or inadequately treated TB * Has received protocol-specified prohibited medicines, including known exposure to any type of anti-TL1A therapy

Locations (184)

Outcomes

Primary Outcomes

Percentage of Participants with Clinical Remission at Week 12

Percentage of participants achieving Modified Mayo Score (mMS) \<=2 with stool frequency subscore (SFS) = 0 or 1 (up to 1-2 stools more than normal), rectal bleeding subscore (RBS) = 0 (no blood seen) and endoscopic subscore (ES) = 0 or 1 (normal appearance of mucosa or mild disease) at Week 12. mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: At Week 12

Percentage of Participants with Clinical Remission at Week 52

Percentage of participants achieving mMS \<= 2 with SFS = 0 or 1 (up to 1-2 stools more than normal), RBS = 0 (no blood seen) and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 52. mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: At Week 52

Secondary Outcomes

Change in Partial Modified Mayo Score (pmMS)

Change in pmMS from baseline to Week 2. pmMS is a composite score of ulcerative colitis signs and symptoms activity given by the sum of the SFS and RBS. SFS is measured on a scale from 0 (normal number of stools) to 3 (5 or more stools than normal). RBS is measured on a scale from 0 (no blood seen) to 3 (blood alone passed).

Time frame: Baseline to Week 2

Percentage of Participants with Endoscopic Improvement

Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 12.

Time frame: At Week 12

Percentage of Participants with Endoscopic Remission

Data from ClinicalTrials.gov

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Digestive Health Specialists of the Southeast (Gastroenterology Associates of Dothan) - Dothan

Dothan, Alabama, United States

Om Research LLC

Lancaster, California, United States

University of California Irvine

Orange, California, United States

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

Access Research Institute

Brooksville, Florida, United States

Gastro Florida

Clearwater, Florida, United States

Clinical Research of Osceola, LLC

Kissimmee, Florida, United States

Auzmer Research

Lakeland, Florida, United States

Florida Research Institute - Lakewood

Lakewood Rch, Florida, United States

Homestead Associates in Research, Inc.

Miami, Florida, United States

...and 174 more locations

Percentage of participants achieving endoscopic subscore of 0 (normal appearance of mucosa) at Week 12.

Time frame: At Week 12

Percentage of Participants with Clinical Response

Percentage of participants achieving a decrease in mMS of at least 2 points and 30% from baseline and either a decrease in RBS \>= 1 or RBS = 0 or 1 (no blood seen or stool with streaks of blood) at Week 12. mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. SFS is measured on a scale from 0 (normal number of stools) to 3 (5 or more stools than normal). RBS is measured on a scale from 0 (no blood seen) to 3 (blood alone passed). ES is measured on a scale from 0 (normal appearance of mucosa) to 3 (severe disease).

Time frame: At Week 12

Percentage of Participants with Histologic Improvement

Percentage of participants achieving a histologic improvement, defined as Geboes \<=3.1 at Week 12. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 12

Percentage of Participants with Histologic Remission

Percentage of participants achieving a histologic remission, defined as Geboes \<2B at Week 12. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 12

Percentage of Participants with Histologic-Endoscopic Mucosal Improvement

Percentage of participants achieving Geboes \<= 3.1 and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 12. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 12

Percentage of Participants with Histologic-Endoscopic Remission

Percentage of participants achieving Geboes \< 2 and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 12. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 12

Percentage of Participants with Maintenance of Remission

Percentage of participants with clinical remission at both Week 12 and Week 52. Clinical remission is defined as mMS \<= 2 with SFS = 0 or 1 (up to 1-2 stools more than normal), RBS = 0 (no blood seen) and ES = 0 or 1 (normal appearance of mucosa or mild disease). mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: Week 12 and Week 52

Percentage of Participants with Corticosteroid-Free Remission

Percentage of participants in clinical remission at Week 52 with no corticosteroid use at least 8 weeks prior to Week 52. Clinical remission is defined as mMS \<= 2 with SFS = 0 or 1 (up to 1-2 stools more than normal), RBS = 0 (no blood seen) and ES = 0 or 1 (normal appearance of mucosa or mild disease). mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: At Week 52

Percentage of Participants with Endoscopic Improvement

Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 52.

Time frame: At Week 52

Percentage of Participants with Endoscopic Remission

Percentage of participants achieving endoscopic subscore of 0 (normal appearance of mucosa) at Week 52.

Time frame: At Week 52

Percentage of Participants with Histologic Improvement

Percentage of participants achieving histologic improvement defined as Geboes \<= 3.1 at Week 52.

Time frame: At Week 52

Percentage of Participants with Histologic Remission

Percentage of participants achieving histologic remission defined as Geboes \<2B at Week 52.

Time frame: At Week 52

Percentage of Participants with Histologic-Endoscopic Mucosal Improvement

Percentage of participants achieving Geboes \<= 3.1 and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 52. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 52

Percentage of Participants with Histologic-Endoscopic Remission

Percentage of participants achieving Geboes \< 2 and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 52. Geboes is a grading system for histologic ulcerative colitis disease activity with scores ranging from 0 (no activity) to 5.4 (ulcer or granulation tissue).

Time frame: At Week 52

Percentage of Participants with Clinical remission: Among Biomarker-Defined Subgroups of Participants

Percentage of participants achieving mMS \<= 2 with SFS = 0 or 1 (up to 1-2 stools more than normal), RBS = 0 (no blood seen) and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 12 in biomarker-defined subgroups. mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: At Week 12

Percentage of Participants with Clinical remission: Among Biomarker-Defined Subgroups of Participants

Percentage of participants achieving mMS \<= 2 with SFS = 0 or 1 (up to 1-2 stools more than normal), RBS = 0 (no blood seen) and ES = 0 or 1 (normal appearance of mucosa or mild disease) at Week 52 in biomarker-defined subgroups. mMS is a composite score of ulcerative colitis disease activity, given by the sum of three subscores: SFS, RBS and ES. Each subscore is measured on a scale from 0 to 3, with higher values associated with greater severity.

Time frame: At Week 52

Percentage of Participants with Endoscopic Improvement: Among Biomarker-Defined Subgroups of Participants

Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 12 in biomarker-defined subgroups.

Time frame: At Week 12

Percentage of Participants with Endoscopic Improvement: Among Biomarker-Defined Subgroups of Participants

Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 52 in biomarker-defined subgroups.

Time frame: At Week 52

Change in Bowel Urgency

Change in bowel urgency from baseline through Week 52. Bowel urgency is measured on a scale from 0 (None) to 4 (Severe).

Time frame: Baseline through Week 52

Change in Abdominal Pain

Change in abdominal pain from baseline through Week 52. Abdominal pain is measured on a scale from 0 (None) to 4 (Severe).

Time frame: Baseline through Week 52

Change in Fatigue

Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) from baseline to Week 12 and Week 52. FACIT-Fatigue is a 13-item self-reported assessment of the level and impact of fatigue. The overall FACIT-Fatigue score ranges between 0 and 52, with higher scores associated with better quality of life concerns related to fatigue.

Time frame: Baseline to Week 12 and Week 52

Change in Health-Related Quality of Life

Change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from baseline to Week 12 and Week 52. IBDQ is a 32-item self-reported assessment of health-related quality of life in participants with inflammatory bowel disease. The overall IBDQ score ranges from 32 to 224, with higher scores associated with better health-related quality of life.

Time frame: Baseline to Week 12 and Week 52

Overall Change in UC Symptoms

Patient Global Impression of Change (PGIC) from baseline to Weeks 2, 12 and 52. PGIC measures overall change in ulcerative colitis symptoms from "Much better" to "Much worse".

Time frame: Baseline to Week 2, Week 12, and Week 52

Overall Severity in UC Symptoms

Patient Global Impression of Severity (PGIS) from baseline to Weeks 2, 12 and 52. PGIS measures severity of ulcerative colitis symptoms from "None" to "Very severe".

Time frame: Baseline to Week 2, Week 12, and Week 52

Incidence and Severity of Adverse Events (AEs)

Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest.

Time frame: Up to 70 Weeks after Baseline