A Maintenance Study to Investigate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Crohn's Disease

Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical response 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.

Time frame: Week 40

Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving SES-CD endoscopic remission at 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.

Time frame: Week 40

US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical remission and endoscopic remission at 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.

Time frame: Week 40

EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving PRO-2 clinical remission and endoscopic remission at 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.

Time frame: Week 40

US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving PRO-2 clinical remission at 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.

Time frame: Week 40

EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving CDAI clinical remission at 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.

Time frame: Week 40

US/FDA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving corticosteroids free CDAI clinical remission at 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.

Time frame: Week 40

EU/EMA Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants achieving corticosteroids free PRO-2 remission at 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.

Time frame: Week 40

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

Time frame: 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)

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.

Time frame: Week 40

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)

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.

Time frame: Week 40

Pivotal Maintenance Sub-Study Cohort 1: Change from Baseline in PROMIS-Fatigue Short Form 7a T-score at 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.

Time frame: Baseline, Week 40

Pivotal Maintenance Sub-Study Cohort 1: Change from Baseline in IBDQ total score at 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.

Time frame: Baseline, Week 40

Pivotal Maintenance Sub-Study Cohort 1: Proportion of participants with no bowel urgency by NRS at 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".

Time frame: Week 40

Pivotal Maintenance Sub-Study Cohort 1: Incidence of CD related hospitalization by Week 40

Time frame: Week 0 through Week 40

Pivotal Maintenance Sub-Study Cohort 1: Serum concentrations of duvakitug measured over time

Time frame: Week 0 through Week 40

Pivotal Maintenance Sub-Study Cohort 1: Incidence of treatment-emergent antidrug antibody (ADA) against duvakitug

Time frame: 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

Time frame: 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

Time frame: Week 40 of pivotal maintenance through 45 days after last dose