Ulcerative Colitis
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 maintenance 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 286 weeks including: * 40-week Pivotal Maintenance Sub-Study * 240-week Open-Label Extension (OLE) Sub-Study * 45-day Follow-up Visit Note: For the participants who do not enroll into OLE Sub-Study, the duration will be up to 46 weeks, including the 40-week maintenance period and a 45-day follow-up visit. The treatment duration may be up to 280 weeks including: * 40 weeks in Pivotal Maintenance Sub-Study * 240 weeks in OLE Sub-Study The total number of on-site visit will be up to 32: * 21 visits in the Pivotal Maintenance Sub-Study. * 11 visits in the OLE Sub-Study.
Interventions
DRUGDuvakitug
Pharmaceutical form: Injection solution Route of administration: SC injection
DRUGPlacebo
Pharmaceutical form:Injection solution-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 Baseline. (Where locally permissible, participants 16 to \<18 years of age who meet the definition of Tanner stage 5 for development) * Pivotal Maintenance Sub-Study: Participants who achieved clinical response and completed endoscopy at the end of SUNSCAPE-1 * OLE Sub-Study: Participants who complete the Pivotal Maintenance Sub-Study or participation in the TV48574-IMM-20038 Study
Exclusion criteria
* Participants with medical or compliance conditions that are deemed unsuitable for the study by the investigator * Participants with a known hypersensitivity to duvakitug that makes the participant unsuitable for the study by the investigator 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 |
|---|---|---|
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving clinical remission by modified Mayo Score (mMS). | Week 40 | Mayo Score is a composite index designed to measure UC disease activity. The score ranges from 0 to 9 with higher scores indicating greater disease severity. Clinical remission is defined as mMS score of 0 to 2, including SFS of 0 or 1, RBS of 0, and mMES of 0 or 1 (score of 1 modified to exclude friability) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with endoscopic improvement. | Week 40 | 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). |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving histologic endoscopic mucosal improvement. | Week 40 | 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. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with corticosteroid-free clinical remission. | Week 40 | — |
| Proportion of participants with no bowel urgency. | Week 40 | 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". |
| Pivotal Maintenance Sub-Study Cohort 1: Change from Baseline in PROMIS-Fatigue Short Form 7a T-score. | Baseline, Week 40 | The PROMIS Fatigue Short Form 7a uses a 5-point Likert scale for each of its 7 items, resulting in a raw score range of 7 to 35. This raw score is then converted into a T-score, with a mean of 50 and a standard deviation of 10, based on US national norms. Higher Tscores indicate greater fatigue. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with endoscopic remission. | Week 40 | Endoscopic remission is defined as mMES of 0. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving clinical remission by mMS, in the subset of participants who achieved clinical remission by mMs at the end of induction period (maintenance of clinical remission). | Week 40 | 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. Mayo Score is a composite index designed to measure UC disease activity. The score ranges from 0 to 9 with higher scores indicating greater disease severity. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with no abdominal pain by Numerical Rating Scale (NRS). | Week 40 | 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"). |
| Pivotal Maintenance Sub-Study Cohort 1: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score | Week 40 | 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. |
| Pivotal Maintenance Sub-Study Cohort 1: Incidence of UC-related hospitalizations. | Week 0 through Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with symptomatic (stool-frequency sub score [SFS] and = rectal bleeding sub score [RBS]) remission. | Week 40 | Symptomatic response is defined as ≥30% decrease from baseline in the composite clinical endpoint of the sum of SFS and RBS. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving clinical remission and no steroid use from the baseline to the time of endpoint analysis. | Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Incidence of Treatment-Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Treatment-Emergent Serious Adverse Events (TESAEs), and TEAEs leading to permanent study intervention discontinuation. | Week 0 through 45 days after last dose | — |
| Pivotal Maintenance Sub-Study Cohort 1: Serum concentration of duvakitug measured over time. | Week 0 through Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Incidence of treatment-emergent Anti-Drug Antibodies (ADA) against duvakitug. | Week 0 through Week 40 | — |
| Open-Label Extension Sub-Study: Incidence of Treatment-Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Treatment-Emergent Serious Adverse Events (TESAEs), and TEAEs leading to permanent study intervention discontinuation. | Week 40 of pivotal maintenance through 45 days after last dose | — |
Countries
Japan, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed