A Study to Assess the Efficacy and Safety of Induction Therapy With Afimkibart (Also Known as RO7790121) in Participants With Moderately to Severely Active Ulcerative Colitis
- Conditions
- Moderately to Severely Active Ulcerative Colitis
- Interventions
- Drug: AfimkibartDrug: Placebo
- Registration Number
- NCT06588855
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This Phase III, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of induction therapy with Afimkibart (RO7790121) compared with placebo in participants with moderately to severely active ulcerative colitis (UC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Afimkibart Afimkibart Participants will receive afimkibart intravenously (IV) followed by afimkibart subcutaneous (SC) injection. Placebo Placebo Participants will receive placebo IV followed by placebo SC.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Clinical Remission: Among Biomarker-Defined Subgroups of Participants At Week 12 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.
Change in Bowel Urgency Baseline through Week 12 Change in bowel urgency from baseline through Week 12. Bowel urgency is measured on a scale from 0 (None) to 4 (Severe).
Change in Partial Modified Mayo Score (pmMS) From baseline to Week 2 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).
Percentage of Participants with Endoscopic Improvement At Week 12 Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 12.
Percentage of Participants with Endoscopic Remission At Week 12 Percentage of participants achieving endoscopic subscore of 0 (normal appearance of mucosa) at Week 12.
Percentage of Participants with Clinical Response At Week 12 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).
Percentage of Participants with Histologic Improvement At Week 12 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).
Percentage of Participants with Histologic Remission At Week 12 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).
Participants with Histologic-Endoscopic Mucosal Improvement At Week 12 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).
Percentage of Participants with Histologic-Endoscopic Remission At Week 12 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).
Percentage of Participants with Endoscopic Improvement: Among Biomarker-Defined Subgroups of Participants At Week 12 Percentage of participants achieving endoscopic subscore of 0 or 1 (normal appearance of mucosa or mild disease) at Week 12 in biomarker-defined subgroups.
Change in Abdominal Pain Baseline through Week 12 Change in abdominal pain from baseline through Week 12. Abdominal pain is measured on a scale from 0 (None) to 4 (Severe).
Change in Fatigue Baseline to Week 12 Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) from baseline to Week 12. 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.
Change in Health-Related Quality of Life Baseline to Week 12 Change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from baseline to Week 12. 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.
Overall Change in UC Symptoms Baseline to Week 2 and Week 12 Patient Global Impression of Change (PGIC) from baseline to Weeks 2 and 12. PGIC measures overall change in ulcerative colitis symptoms from "Much better" to"Much worse".
Overall Severity in UC Symptoms Baseline to Week 2 and Week 12 Patient Global Impression of Severity (PGIS) from baseline to Weeks 2 and 12. PGIS measures severity of ulcerative colitis symptoms from "None" to "Very severe".
Incidence and Severity of Adverse Events (AEs) Up to 30 Weeks after Baseline Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest.
Trial Locations
- Locations (152)
Advanced Medical Research Center
🇺🇸Port Orange, Florida, United States
Gastro Health Partners, LLC
🇺🇸New Albany, Indiana, United States
Instituto Lobus Unimed Volta Redonda
🇧🇷Volta Redonda, Rio de Janeiro, Brazil
Newdata Clinical Trials
🇧🇷Aracaju, Sergipe, Brazil
Centro Paulista de Investigacao Clinica - CEPIC
🇧🇷São Paulo, São Paulo, Brazil
Second Multiprofile Hospital For Active Treatment-Sofia
🇧🇬Sofia Town, Sofia, Bulgaria
Kingsway Hospital
🇮🇳Nagpur (urban), Maharashtra, India
Mayo Clinic Hospital
🇺🇸Scottsdale, Arizona, United States
Om Research LLC
🇺🇸Apple Valley, California, United States
Valley View Internal Medicine
🇺🇸Garden Grove, California, United States
Scroll for more (142 remaining)Advanced Medical Research Center🇺🇸Port Orange, Florida, United States