Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial.

Abstract

Crohn's disease is a chronic, relapsing inflammatory disease of the gastrointestinal tract. We aimed to assess the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A monoclonal antibody, in adults with moderately to severely active Crohn's disease. In this multicentre, placebo-controlled, phase 2b study, we enrolled adults (aged 18-75 years) with moderately to severely active Crohn's disease (including inadequate response, loss of response, or intolerance to previous therapies). We randomly assigned (1:1:1) participants to receive 2250 mg duvakitug loading dose subcutaneously, followed by duvakitug 450 mg or 900 mg every 2 weeks, or placebo loading dose, then placebo every 2 weeks. The primary endpoint, endoscopic response (≥50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease) at week 14, was analysed using Bayesian methodology. A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was at least 0·90. Analyses were done in the modified intention-to-treat population, which included all patients who received at least one dose of their assigned treatment. This trial was registered with ClinicalTrials.gov, NCT05499130, and has been completed. Patients were enrolled from Sept 30, 2022, to Nov 12, 2024. We screened 275 patients with Crohn's disease, of whom 139 (51%) patients were randomly assigned to receive either duvakitug 450 mg (n=46), duvakitug 900 mg (n=47), or placebo (n=46). One patient in the duvakitug 900 mg did not receive study drug; the modified intention-to-treat population therefore included 46 patients in the 450 mg group, 46 in the 900 mg group, and 46 in the placebo group. 78 (57%) patients were previously exposed to at least one advanced therapy. The mean age of enrolled patients was 39·5 years (SD 14·7); 58 (42%) were female, 80 (58%) were male, and 131 (95%) were White. 12 (26%) of 46 patients in the duvakitug 450 mg group, 22 (48%) of 46 in the duvakitug 900 mg group, and six (13%) of 46 in the placebo group had an endoscopic response at week 14. The difference in posterior mean response rates versus placebo was 13% (95% credible interval -3 to 29) for duvakitug 450 mg and 33% (16 to 50) for duvakitug 900 mg, with posterior probabilities of superiority of 0·94 for duvakitug 450 mg and greater than 0·99 for duvakitug 900 mg. Adverse events occurred in 31 (67%) of 46 patients in the duvakitug 450 mg group, 20 (43%) of 46 in the duvakitug 900 mg group, and 22 (48%) of 46 in the placebo group. The most frequent adverse events were nasopharyngitis (two in the 450 mg group, three in the 900 mg group, and three in the placebo group) and headache (four in the 450 mg group, one in the 900 mg group, and one in the placebo group). Serious adverse events occurred in six (13%) patients in the duvakitug 450 mg group, one (2%) in the duvakitug 900 mg group, and five (11%) in the placebo group. Duvakitug showed significant evidence for endoscopic response versus placebo in patients with moderately to severely active Crohn's disease, with no safety concerns identified. Teva and Sanofi.