Efficacy and Safety of Duvakitug for Induction Therapy in Participants with Moderately to Severely Active Ulcerative Colitis: A Phase 3, Randomized, Placebo-Controlled Study

The primary objective of this study is to evaluate the efficacy of duvakitug as induction therapy in participants with moderately to severely active ulcerative colitis compared to placebo. 5

The secondary objectives include:

• Assessment of efficacy using multiple measures of disease activity. 5
• Evaluation of the safety profile of duvakitug compared to placebo. 4
• Investigation of the pharmacokinetics and immunogenicity of duvakitug. 6

The study involves a total of 1134 participants diagnosed with ulcerative colitis. The population includes both male and female patients, including vulnerable groups. Eligible participants are aged between 18 and 80 years, although locally permitted inclusion may extend to individuals aged 16 to <18 years who meet the Tanner Stage 5 developmental criteria. Inclusion requires a confirmed diagnosis of moderately to severely active disease for a minimum of 3 months prior to baseline. Participants must have demonstrated an inadequate response, loss of response, or intolerance to conventional therapies or advanced treatments.

This multicenter, multinational, randomized, double-blind, placebo-controlled, Phase 3 study is an induction trial designed to evaluate the efficacy and safety of duvakitug in individuals with moderately to severely active ulcerative colitis. Participants will receive either duvakitug as a subcutaneous injection or a matched placebo. The research methodology aims to assess the proportion of participants achieving clinical remission as the primary endpoint. Secondary endpoints include endoscopic improvement, clinical response via the modified Mayo Score, and histological mucosal improvement, among other measures. The study procedure involves a screening visit to confirm diagnosis and eligibility, followed by subsequent study visits to monitor clinical response and safety. Assessment of treatment-emergent adverse events and the incidence of anti-drug antibodies will be conducted to determine the safety profile. The overall duration of the study is estimated to conclude by September 2028.

The experimental medication, duvakitug, is administered as a solution for injection. The drug is delivered via subcutaneous injection for the treatment of ulcerative colitis.

A matched placebo is utilized as the comparator treatment in this randomized, double-blind, placebo-controlled study. The placebo is designed to be identical to the test product to maintain the blinding of the trial.

The primary efficacy endpoint is the proportion of participants achieving clinical remission in patients with moderately to severely active ulcerative colitis.

Secondary efficacy parameters include:

• Proportion of participants achieving endoscopic improvement.
• Proportion of participants achieving clinical response as measured by the modified Mayo Score.
• Proportion of participants achieving histological endoscopic mucosal improvement.
• Change from baseline in the PROMIS-Fatigue Short Form 7a T-score.
• Proportion of participants with symptomatic remission, defined by stool frequency sub score and rectal bleeding sub score.
• Proportion of participants with no bowel urgency.
• Proportion of participants reporting no nocturnal bowel movements.
• Proportion of participants achieving endoscopic remission.
• Proportion of participants with no abdominal pain as assessed by the Numeric Rating Scale.
• Change from baseline in the Inflammatory Bowel Disease Questionnaire total score.
• Proportion of participants experiencing UC-related hospitalization.
• Proportion of participants achieving clinical remission without steroid use.
• Serum concentration of duvakitug measured over time.
• Incidence of anti-drug antibodies against duvakitug.