Crohn's Disease
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled, maintenance, Phase 3 study to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active Crohn's Disease (CD). 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 the Pivotal Maintenance Sub-Study * 240 weeks in OLE Sub-Study The total number of on-site visits will be up to 43: - 21 visits in the Pivotal Maintenance Sub-Study - 22 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 STARSCAPE-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 patient's potential participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Co-primary endpoints EU/EMA: Pivotal Maintenance Sub-Study Cohort 1 Proportion of participants achieving clinical remission per PRO-2 at Week 40 | Week 40 | Clinical Remission 2-item patient-reported outcome (PRO-2): average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline. |
| Co-primary endpoints US/FDA: Pivotal Maintenance Sub-Study Cohort 1 Proportion of participants achieving clinical remission (CDAI) at Week 40 | Week 40 | Clinical Remission by Crohn's Disease Activity Index (CDAI): CDAI score \<150. The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. |
| Proportion of participants achieving Endoscopic Response (SES-CD) at Week 40 | Week 40 | The SES-CD is a standardized method for evaluating disease activity. Score ranges from 0 to 56, where higher scores represent more severe disease. Endoscopic Response by SES-CD is a decrease in SES-CD ≥50% from Baseline (or a decrease of at least 2 points for participants with a Baseline score of 4 or more, and isolated ileal disease) based on central reading. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical response Week 40 | Week 40 | The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. Clinical Response by CDAI: decrease in CDAI score of 100 points or more from Baseline. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving SES-CD endoscopic remission at Week 40 | Week 40 | The SES-CD is a standardized method for evaluating disease activity. Score ranges from 0 to 56, where higher scores represent more severe disease. Endoscopic remission: a SES-CD ≤4 points (SES-CD ≤2 points for isolated ileal disease) and a SES-CD decrease ≥2 points with no SES-CD sub score \>1 point from Baseline. |
| US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical remission and endoscopic remission at Week 40 | Week 40 | The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. The SES-CD is a standardized method for evaluating disease activity. Score ranges from 0 to 56, where higher scores represent more severe disease. Clinical Remission by CDAI: CDAI score \<150. Endoscopic remission: a SES-CD ≤4 points (SES-CD ≤2 points for isolated ileal disease) and a SES-CD decrease ≥2 points with no SES-CD sub score \>1 point from Baseline. |
| EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving PRO-2 clinical remission and endoscopic remission at Week 40 | Week 40 | Clinical Remission PRO-2: average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline. The SES-CD is a standardized method for evaluating disease activity. Score ranges from 0 to 56, where higher scores represent more severe disease. Endoscopic remission: a SES-CD ≤4 points (SES-CD ≤2 points for isolated ileal disease) and a SES-CD decrease ≥2 points with no SES-CD sub score \>1 point from Baseline. |
| US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving PRO-2 clinical remission at Week 40 | Week 40 | Clinical Remission PRO-2: average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline. |
| EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical remission at Week 40 | Week 40 | Clinical Remission by CDAI: CDAI score \<150. The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. |
| US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving corticosteroids free CDAI clinical remission at Week 40 | Week 40 | Clinical Remission by CDAI: CDAI score \<150 and without corticosteroid use for CD for at least 12 weeks prior to assessment. The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. |
| EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving corticosteroids free PRO-2 remission at Week 40 | Week 40 | Clinical Remission PRO-2: average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline and without corticosteroid use for CD for at least 12 weeks prior to assessment. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving ulcer-free endoscopy (in the subset of participants with ulcers at Baseline) at Week 40 | Week 40 | — |
| US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving clinical remission per CDAI at Week 40 in the subset of participants with clinical remission per CDAI at Week 0 (maintenance of clinical remission per CDAI) | Week 40 | Clinical Remission by CDAI: CDAI score \<150. The CDAI is a measure of disease activity based on symptoms, signs, and a laboratory test. Scores on the CDAI scale range from 0 to 600, with scores below 150 indicating relative disease quiescence (remission), 150 to 219 indicating mild disease activity, 220 to 450 indicating moderate activity, and scores exceeding 450 indicating severe disease. |
| EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving clinical remission per PRO-2 at Week 40 in the subset of participants with clinical remission per PRO-2 at Week 0 (maintenance of clinical remission per PRO-2) | Week 40 | Clinical Remission PRO-2: average daily stool frequency (SF) ≤3 and not worse than the Baseline, and average daily abdominal pain (AP) ≤1 and not worse than the Baseline. |
| Pivotal Maintenance Sub-Study Cohort 1: Change from Baseline in PROMIS-Fatigue Short Form 7a T-score at Week 40 | 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 T-scores indicate greater fatigue. |
| Pivotal Maintenance Sub-Study Cohort 1: Change from Baseline in IBDQ total score at Week 40 | Baseline, Week 40 | Inflammatory Bowel Disease Questionnaire (IBDQ) instrument consist of 32 items exploring 4 dimensions: "bowel symptoms" (10 items), "systemic symptoms" (5 items), "emotional function" (12 items) and "social function" (5 items). The total IBDQ total score ranges from 32 to 224 with higher score indicating better quality of life. |
| Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with no bowel urgency by NRS at Week 40 | Week 40 | Numeric Rating Scale (NRS) for bowel urgency measures 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: Incidence of CD related hospitalization by Week 40 | Week 0 through Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Incidence of treatment-emergent antidrug antibody (ADA) against duvakitug | Week 0 through Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Serum concentrations of duvakitug measured over time | Week 0 through Week 40 | — |
| Pivotal Maintenance Sub-Study Cohort 1: Incidence of treatment-emergent adverse events (TEAEs), TEAE of special interest (TEAESIs), TE serious adverse events (TESAEs) and TEAEs leading to permanent study intervention discontinuation | Week 0 through 45 days after last dose | — |
| Open-Label Extension Sub-Study: Incidence of TEAEs, TEAESIs, TESAEs, and TEAEsleading to permanent study intervention discontinuation | Week 40 of pivotal maintenance through 45 days after last dose | — |
Countries
United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed