Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Duvakitug for Induction Therapy in Moderately to Severely Active Crohn's Disease

The primary objective of this study is to assess the efficacy of duvakitug as induction therapy in participants with moderately to severely active Crohn’s disease compared to a placebo. 5

The secondary objectives include:

• Evaluation of efficacy through multiple measures of disease activity. 5
• Assessment of safety profiles in participants receiving induction therapy. 4
• Evaluation of pharmacokinetics and immunogenicity. 6

This study involves a total of 1,358 patients diagnosed with Crohn’s disease. The study population includes both males and females, including vulnerable populations. Participants must be aged between 18 and 80 years, although individuals aged 16 to <18 years may be included if they meet the Tanner Stage 5 developmental criteria. Eligible individuals must have a confirmed diagnosis of moderately to severely active disease for a minimum of 3 months prior to baseline. Inclusion requires a demonstrated inadequate response, loss of response, or intolerance to conventional therapies or advanced therapies. The cohort is characterized by the presence of immune system diseases.

This is a multicenter, multinational, randomized, double-blind, placebo-controlled, Phase 3 induction study designed to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active Crohn’s Disease. The study involves the administration of duvakitug or a matched placebo via subcutaneous injection. Following a screening visit to confirm eligibility, participants are randomized to receive the study intervention. The primary objectives include the assessment of clinical remission and endoscopic response at Week 12. Secondary endpoints include evaluations of corticosteroid-free remission, changes in patient-reported outcomes, and the monitoring of treatment-emergent adverse events. The study also monitors serum concentrations of the test product and the incidence of anti-drug antibodies. Specific procedures and follow-up assessments are conducted to measure therapeutic response and safety throughout the induction period.

Duvakitug is an experimental investigational medicinal product provided as a solution for injection. This substance is administered via subcutaneous injection to participants diagnosed with moderately to severely active Crohn’s disease.

A matched placebo is utilized as a comparator treatment. This placebo is formulated to be identical to the test product to maintain the double-blind design of the study.

The efficacy of duvakitug in participants with moderately to severely active Crohn’s disease is assessed through several co-primary endpoints at Week 12. These include the proportion of participants achieving clinical remission as measured by the Crohn’s Disease Activity Index (CDAI) and the proportion achieving endoscopic response determined by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Additionally, the patient-reported outcome (PRO-2) is utilized to evaluate clinical remission at this timepoint.

Secondary efficacy assessments at Week 12 include:

• Proportion of participants achieving CDAI clinical response.
• Proportion of participants achieving both CDAI clinical response and endoscopic response.
• Proportion of participants achieving endoscopic SES-CD remission.
• Proportion of participants achieving clinical remission per PRO-2.
• Proportion of participants achieving ulcer-free endoscopy in a subset with baseline ulcers.
• Change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a T-score.
• Change from baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) total score.
• Proportion of participants with no bowel urgency measured by the Numeric Rating Scale (NRS).
• Proportion of participants experiencing hospitalizations.
• Proportion of participants achieving corticosteroid free remission per CDAI or PRO-2 in a subset receiving corticosteroids at baseline.
• Proportion of participants achieving combined CDAI clinical remission and endoscopic remission.