An Induction Study to Investigate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: Placebo
- Registration Number
- NCT07184996
- Lead Sponsor
- Sanofi
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 980
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Duvakitug - dose 1 Duvakitug Subcutaneous (SC) injection as per protocol Duvakitug - dose 2 Duvakitug SC injection as per protocol Placebo Placebo SC injection as per protocol
- Primary Outcome Measures
Name Time Method 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 (mMES) 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 Outcome Measures
Name Time Method Proportion of participants who achieve endoscopic improvement. Week 12 Endoscopic improvement is defined as mMES 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