Moderately to Severely Active Ulcerative Colitis
Conditions
Brief summary
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).
Interventions
DRUGAfimkibart
Afimkibart will be administered as IV infusion. Afimkibart will be administered as SC injection.
DRUGPlacebo
Placebo matching IV afimkibart. Placebo matching SC afimkibart.
Sponsors
Hoffmann-La Roche
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Clinical Remission at Week 12 | 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. |
| Percentage of Participants with Clinical Remission at Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Partial Modified Mayo Score (pmMS) | 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). |
| Percentage of 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 Maintenance of Remission | Week 12 and Week 52 | 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. |
| Percentage of Participants with Corticosteroid-Free Remission | At Week 52 | 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. |
| 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. |
| 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 Bowel Urgency | Baseline through Week 52 | Change in bowel urgency from baseline through Week 52. Bowel urgency is measured on a scale from 0 (None) to 4 (Severe). |
| Change in Abdominal Pain | Baseline through Week 52 | Change in abdominal pain from baseline through Week 52. Abdominal pain is measured on a scale from 0 (None) to 4 (Severe). |
| Change in Fatigue | Baseline to Week 12 and Week 52 | 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. |
| Change in Health-Related Quality of Life | Baseline to Week 12 and Week 52 | 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. |
| Overall Change in UC Symptoms | Baseline to Week 2, Week 12, and Week 52 | 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". |
| Overall Severity in UC Symptoms | Baseline to Week 2, Week 12, and Week 52 | 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". |
| Incidence and Severity of Adverse Events (AEs) | Up to 70 Weeks after Baseline | Incidence and severity of AEs, including serious AEs, AEs leading to treatment discontinuation and AEs of special interest. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed