Ulcerative Colitis
Conditions
Brief summary
This is a multinational, multicenter, randomized, double-blind, placebo-controlled, Phase 3 induction study to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active Ulcerative Colitis (UC). Study details include: The study duration may be up to 35 weeks with: * Screening period * 12-week Sub-Study 1 (Single-Arm Open-Label Feeder Induction) or Sub-Study 2 (Pivotal Induction) * 12-week Sub-Study 3 (Extended Induction for non-responders) * 45 days follow-up visit for participants who do not enroll into the maintenance study (EFC18359) The treatment duration will be up to 12 weeks in each sub-study. The number of scheduled on-site visits will be up to 8 for the Sub-Study 1 and Sub Study 2 or a maximum of 15 visits for participants completing extended induction.
Interventions
DRUGDuvakitug
Pharmaceutical form:Solution for Injection-Route of administration:SC injection
DRUGPlacebo
Pharmaceutical form:Solution for injection-Route of administration:SC injection
Sponsors
Sanofi
Teva Branded Pharmaceutical Products R&D LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants aged ≥18 and ≤80 years of age at Screening. Where permitted locally, participants 16 to \<18 years of age who meet the definition of Tanner Stage 5 for development * Confirmed diagnosis of moderately to severely active UC for at least 3 months prior to Baseline * Demonstrated inadequate response, have shown loss of response or intolerance to conventional therapies or advanced therapies
Exclusion criteria
* Participants with Crohn's Disease (CD), indeterminate colitis * Current diagnosis of Ulcerative Proctitis * Participants with surgical bowel resection within the past 3 months prior to Baseline, or a history of \>3 bowel resections * Prior or current high-grade gastrointestinal (GI) dysplasia * Participants on treatment with but not on stable doses of conventional therapies prior to baseline * Participants with prohibited medications or therapies prior to baseline * Participants with previous exposure to anti-TL1A investigational therapy The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving clinical remission. | Week 12 | Clinical remission is defined as modified Mayo Score (mMS) score of 0 to 2, including SFS of 0 or 1, RBS of 0, and modified Mayo Endoscopic Score (MES) of 0 or 1 (score of 1 modified to exclude friability). mMS is a composite index designed to measure UC disease activity. The score ranges from 0 to 9 with higher scores indicating greater disease severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who achieve endoscopic improvement. | Week 12 | Endoscopic improvement is defined as MES of 0 or 1 (score of 1 excludes friability). Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Proportion of participants achieving clinical response by modified Mayo Score (mMS). | Week 12 | Clinical response is defined as a decrease from baseline in the mMS of ≥2 points and at least a 30% reduction from baseline, and a decrease in RB subscore of ≥1 or an absolute RB subscore of 0 or 1. mMS is a composite index designed to measure UC disease activity. The score ranges from 0 to 9 with higher scores indicating greater disease severity. |
| Proportion of participants achieving histological endoscopic mucosal improvement. | Week 12 | Histological endoscopic mucosal improvement is defined as MES of 0 or 1 without the evidence of friability and Geboes Score ≤3.1. The Geboes score has 6 grades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Change from baseline in PROMIS-Fatigue Short Form 7a T-score. | Baseline, Week 12 | The PROMIS-Fatigue Short Form 7 is a tool that assessesfatigue severity and its impact on daily functioning over the past week. |
| Proportion of participants with symptomatic (SFS and RBS) remission | Week 12 | Symptomatic remission (SF and RB): stool-frequency sub score (SFS ) of 0 or 1, and rectal bleeding sub score (RBS) of 0. |
| Proportion of participants with no bowel urgency. | Week 12 | The NRS for bowel urgency is a patient-reported tool designed to measure the severity of bowel urgency-the sudden or immediate need to have a bowel movement-experienced in the past 24 hours. This tool utilizes an 11-point scale for evaluation, where 0 represents "no urgency" and 10 signifies the "worst possible urgency". |
| Proportion of participants reporting no nocturnal bowel movements. | Week 12 | — |
| Proportion of participants with symptomatic (stool-frequency sub score [SFS] and = rectal bleeding sub score [RBS]) remission. | Week 4 | Symptomatic response is defined as ≥30% decrease from baseline in the composite clinical endpoint of the sum of SFS and RBS. |
| Proportion of participants who achieve endoscopic remission. | Week 12 | Endoscopic remission is defined as mMES of 0. |
| Proportion of participants with no abdominal pain by Numeric Rating Scale (NRS). | Week 12 | The abdominal pain NRS is a tool to rate the severity of abdominal pain over the past 24 hours using a score of 0 ("no pain") to 10 ("worst possible pain"). |
| Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score. | Baseline, Week 12 | IBDQ is a tool to the quality of life of individuals suffering from IBD. The total score ranges from 32 to 224, with higher scores correlating to a better quality of life. |
| Proportion of participants with UC-related hospitalization. | Baseline through Week 12 | — |
| Proportion of participants achieving clinical remission and no steroid use. | Week 12 | — |
| Incidence of Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs), and TEAEs leading to permanent study intervention discontinuation. | Baseline through 45 days after last dose | — |
| Serum concentration of duvakitug measured over time. | Baseline through Week 12 | — |
| Incidence of treatment-emergent Anti-Drug Antibodies (ADA) against duvakitug. | Baseline through Week 12 | — |
Countries
Canada, Georgia, Japan, Moldova, Poland, Puerto Rico, Serbia, Switzerland, Taiwan, Ukraine, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed