Crohn's Disease
Conditions
Brief summary
This is a multinational, multicenter, randomized, double-blind, placebo-controlled, Phase 3 induction study, comprised of 3 sub-studies, to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active CD. Study details include: The study duration may be up to 35 weeks with: * Up to 5-week 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). * 6 weeks (45 days) follow-up period for participants who do not enroll into the Pivotal Maintenance Study (EFC18327). The treatment duration will be up to 12 weeks in each sub-study. The number of scheduled study visits for participants who continue to the Pivotal Maintenance Study (EFC18327) will be up to 8 (Sub-Study 1 and Sub-Study 2) and up to 15 for participants who enroll in Sub-Study 3.
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 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 Crohn's Disease (CD) for at least 3 months prior to baseline * Demonstrated inadequate response, have shown loss of response or intolerance to conventional therapies or advanced therapies (ATs)
Exclusion criteria
* Participants with Ulcerative Colitis (UC) or indeterminate colitis * Participants with two entire missing segments of the: terminal ileum, right colon transverse colon, sigmoid and left colon, and rectum * Prior or current high-grade gastrointestinal (GI) dysplasia * Participants on treatment with but not on stable doses of conventional therapy prior to baseline * Participants receiving prohibited medications or therapies * 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 |
|---|---|---|
| Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12 | Week 12 | 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. |
| Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving endoscopic response (Simple Endoscopic Score for Crohn's Disease [SES-CD]) at Week 12 | Week 12 | Endoscopic Response is defined as 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. The SES-CD is a standardized method for evaluating disease activity. The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores represent more severe disease. |
| Sub-Study 2: Co-primary endpoints EU/EMA: Proportion of participants achieving clinical remission per 2-item patient-reported outcome (PRO-2) at Week 12 | Week 12 | Clinical Remission per 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. |
| Sub-Study 2: Co-primary endpoints EU/EMA: Proportion of participants achieving endoscopic response (SES-CD) at Week 12 | Week 12 | Endoscopic Response is defined as 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. The SES-CD is a standardized method for evaluating disease activity. The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores represent more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sub-Study 2: Proportion of participants achieving CDAI clinical response at Week 12 | Week 12 | CDAI clinical response is defined as decrease in CDAI score of 100 points or more from baseline. |
| Sub-study 2: Proportion of participants achieving CDAI clinical response and endoscopic response (SES-CD) at Week 12 | Week 12 | CDAI clinical response is defined as decrease in CDAI score of 100 points or more from baseline. Endoscopic Response by SES-CD was defined as 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. |
| Sub-study 2: Proportion of participants achieving endoscopic SES-CD remission at Week 12 | Week 12 | Endoscopic Remission by SES-CD is defined as SES-DC ≤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 |
| Sub-study 2: US/FDA: Proportion of participants achieving clinical remission per PRO-2 at Week 12 | Week 12 | Clinical Remission per PRO-2: average daily SF ≤3 and not worse than the Baseline, and average daily AP ≤1 and not worse than the Baseline. |
| Sub-study 2: EU/EMA: Proportion of participants achievingclinical remission per CDAI at Week 12 | Week 12 | 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. |
| Sub-study 2: Proportion of participants achieving ulcer-free endoscopy (in the subset of participants with ulcers at baseline) at Week 12 | Week 12 | Ulcer-free endoscopy: SES-CD ulcerated surface sub-score of 0 in participants with SES-CD ulcerated surface sub-score ≥1 at Baseline, as scored by a central reader. |
| Sub-study 2: Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a T-score at Week 12 | Baseline, Week 12 | 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. |
| Sub-study 2: Proportion of participants achieving CDAI clinicalresponse at Week 4 | Week 4 | CDAI clinical response is defined as decrease in CDAI score of 100 points or more from baseline. |
| Sub-study 2: US/FDA: Proportion of participants achievingcorticosteroid free remission (in the subset ofparticipants with corticosteroids at baseline) perCDAI at Week 12 | Week 12 | Corticosteroid free remission per CDAI: proportion of participants who discontinue corticosteroid use for CD and achieve clinical remission per CDAI (CDAI score \<150) at Week 12, in participants taking corticosteroids for CD at Baseline. |
| Sub-study 2: EU/EMA: Proportion of participants achievingcorticosteroid free remission per PRO-2 (in thesubset of participants with corticosteroids atbaseline) at Week 12 | Week 12 | Corticosteroid free remission by PRO-2: proportion of participants who discontinue corticosteroid use for CD and achieve clinical remission per PRO-2 (average daily SF ≤3 and not worse than the baseline, and average daily AP ≤1 and not worse than the baseline) at Week 12, in participants taking corticosteroids for CD at Baseline. |
| Sub-study 2: Proportion of participants achieving CDAI clinical remission and endoscopic remission (SES-CD) at Week 12 | Week 12 | Clinical Remission by CDAI: CDAI score \<150. Endoscopic Remission: 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. |
| Sub-study 2: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12 | Baseline, Week 12 | 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. |
| Sub-study 2: Proportion of participants with no bowel urgency byNumeric Rating Scale (NRS) at Week 12 | Week 12 | The NRS for bowel urgency is a well-defined and reliable instrument to evaluate treatment benefits in participants with CD. The 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, from 0 (no urgency) to 10 (worst possible urgency). |
| Sub-study 2: Proportion of participants with CD-related hospitalizations by Week 12 | Baseline through Week 12 | — |
| Sub-study 2: Number of participants with any Treatment Emergent Adverse Events (TEAEs), TEAE of special interest (TEAESIs), TE serious adverse event (TESAEs), and TEAEs leading to permanent study intervention discontinuation | Baseline through 45 days after the last dose | — |
| Sub-study 2: Serum concentrations of duvakitug | Baseline to Week 12 | — |
| Sub-study 2: Incidence of treatment-emergent Anti-drug Antibodies (ADA) against duvakitug | Baseline to Week 12 | — |
Countries
Canada, Georgia, Japan, Moldova, Puerto Rico, South Africa, Switzerland, Taiwan, Ukraine, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed