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

Abstract

Ulcerative colitis is a chronic inflammatory disease affecting the colon and rectum. We aimed to investigate the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A (TL1A) monoclonal antibody, in adults with moderately to severely active ulcerative colitis. In this multicentre, placebo-controlled, phase 2b study, we randomly assigned (1:1:1) adults aged 18-75 years with moderately to severely active ulcerative colitis (including patients with inadequate response, loss of response, or intolerance to previous conventional or advanced therapies) to receive a 2250 mg loading dose of duvakitug (subcutaneously), followed by either 450 mg or 900 mg doses every 2 weeks, or placebo loading dose followed by placebo every 2 weeks. The primary endpoint was clinical remission (modified Mayo score) at week 14, analysed using Bayesian methodology. A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was 0·90 or greater. 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 between Sept 30, 2022 and Nov 12, 2024. We screened 260 patients with ulcerative colitis. Of these, we randomly assigned 137 (53%) patients to receive duvakitug (n=47 450 mg and n=46 900 mg) or placebo (n=44; modified intention-to-treat analysis set). Patients had a mean age of 41·0 years (SD 13·1); 86 (63%) were men, 51 (37%) were women, and 132 (96%) were White. 43 (31%) patients had previous exposure to an approved advanced therapy. 17 (36%) of 47 patients in the duvakitug 450 mg group and 22 (48%) of 46 patients in the duvakitug 900 mg group were in clinical remission at week 14, compared with nine (20%) of 44 patients in the placebo group. Differences in posterior mean response rates versus placebo were 15% (95% credible interval [CrI] -3 to 33) for duvakitug 450 mg and 26% (95% CrI 8 to 44) for duvakitug 900 mg, with posterior probabilities of superiority to placebo exceeding the prespecified threshold for declaring efficacy (0·95 in the 450 mg group and >0·99 in the 900 mg group). Adverse event incidence was similar with duvakitug (23 [49%] of 47 patients in the 450 mg group and 20 [43%] of 46 in the 900 mg group) and placebo (23 [52%] of 44). The most frequently occurring adverse events were anaemia (one in the 450 mg group, one in the 900 mg group, and three in the placebo group) and upper respiratory tract infection (three in the 450 mg group, one in the 900 mg group, and one in the placebo group). One serious adverse event occurred in the 900 mg group (non-infective oophoritis) and one in the placebo group (intracranial haemorrhage). Duvakitug showed significant evidence for clinical remission versus placebo, with no safety concerns identified, in patients with moderately to severely active ulcerative colitis. Teva and Sanofi.