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.
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.
Brief Title
An Induction Study to Investigate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Crohn's Disease
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
800-633-1610
Central Contact Phone Ext
option 6
Central Contact Email
Contact-US@sanofi.com
Completion Date
Completion Date Type
Estimated
Conditions
CROHN'S DISEASE
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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)
* 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
16 Years
NCT Id
NCT07184931
Org Class
Industry
Org Full Name
Sanofi
Org Study Id
EFC18326
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Phase 3, Induction Study to Evaluate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Crohn's Disease
Primary Outcomes
Outcome Description
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.
Outcome Measure
Sub-Study 2: Co-primary endpoints US/FDA: Proportion of participants achieving clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12
Outcome Time Frame
Week 12
Outcome Description
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.
Outcome Measure
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
Outcome Time Frame
Week 12
Outcome Description
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.
Outcome Measure
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
Outcome Time Frame
Week 12
Outcome Description
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.
Outcome Measure
Sub-Study 2: Co-primary endpoints EU/EMA: Proportion of participants achieving endoscopic response (SES-CD) at Week 12
Outcome Time Frame
Week 12
Secondary Ids
Secondary Id
2025-521036-11
Secondary Id
U1111-1314-5319
Secondary Outcomes
Outcome Description
CDAI clinical response is defined as decrease in CDAI score of 100 points or more from baseline.
Outcome Time Frame
Week 12
Outcome Measure
Sub-Study 2: Proportion of participants achieving CDAI clinical response at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: Proportion of participants achieving CDAI clinical response and endoscopic response (SES-CD) at Week 12
Outcome Description
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
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: Proportion of participants achieving endoscopic SES-CD remission at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: US/FDA: Proportion of participants achieving clinical remission per PRO-2 at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: EU/EMA: Proportion of participants achievingclinical remission per CDAI at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: Proportion of participants achieving ulcer-free endoscopy (in the subset of participants with ulcers at baseline) at Week 12
Outcome Description
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.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Sub-study 2: Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a T-score at Week 12
Outcome Description
CDAI clinical response is defined as decrease in CDAI score of 100 points or more from baseline.
Outcome Time Frame
Week 4
Outcome Measure
Sub-study 2: Proportion of participants achieving CDAI clinicalresponse at Week 4
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: US/FDA: Proportion of participants achievingcorticosteroid free remission (in the subset ofparticipants with corticosteroids at baseline) perCDAI at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: EU/EMA: Proportion of participants achievingcorticosteroid free remission per PRO-2 (in thesubset of participants with corticosteroids atbaseline) at Week 12
Outcome Description
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.
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: Proportion of participants achieving CDAI clinical remission and endoscopic remission (SES-CD) at Week 12
Outcome Description
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.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Sub-study 2: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12
Outcome Description
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).
Outcome Time Frame
Week 12
Outcome Measure
Sub-study 2: Proportion of participants with no bowel urgency byNumeric Rating Scale (NRS) at Week 12
Outcome Time Frame
Baseline through Week 12
Outcome Measure
Sub-study 2: Proportion of participants with CD-related hospitalizations by Week 12
Outcome Time Frame
Baseline through 45 days after the last dose
Outcome Measure
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
Outcome Time Frame
Baseline to Week 12
Outcome Measure
Sub-study 2: Serum concentrations of duvakitug
Outcome Time Frame
Baseline to Week 12
Outcome Measure
Sub-study 2: Incidence of treatment-emergent Anti-drug Antibodies (ADA) against duvakitug
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
16
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ruby Greywoode
Investigator Email
rgreywoode@montefiore.org
Investigator Phone
347-671-8211
Investigator Department
Medicine
Investigator Division
Gastroenterology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Please Specify
Categories Mesh Debug
Digestive System --- CROHN DISEASE
Digestive System --- INFLAMMATORY BOWEL DISEASES
Digestive System --- GASTROENTERITIS
Digestive System --- GASTROINTESTINAL DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Digestive System --- INTESTINAL DISEASES
MeSH Terms
CROHN DISEASE
INFLAMMATORY BOWEL DISEASES
GASTROENTERITIS
GASTROINTESTINAL DISEASES
DIGESTIVE SYSTEM DISEASES
INTESTINAL DISEASES