Randomised clinical trial: a placebo‐controlled study of intravenous golimumab induction therapy for ulcerative colitis

Abstract

Background Tumour necrosis factor alpha (TNFα)‐antagonism effectively treats ulcerative colitis (UC). The golimumab clinical programme evaluated subcutaneous (SC) and intravenous (IV) induction, and SC maintenance regimens, in TNFα‐antagonist‐naïve patients with moderate‐to‐severe active UC despite conventional treatment. Aim To evaluate dose–response relationship, select IV golimumab induction doses for continued development, and evaluate the safety and efficacy of selected doses. Methods Adults with Mayo scores of 6–12 and endoscopic subscores ≥2 were enrolled into this multicentre, randomised, double‐blind, placebo‐controlled, integrated Phase 2/3 dose‐finding/dose‐confirming study. In Phase 2, 176 patients were randomised (1:1:1:1) to a single IV infusion of placebo, 1‐, 2‐ or 4‐mg/kg golimumab. While Phase 2 data were analysed to select doses for continued development, 71 additional patients were randomised. Phase 3 enrolment stopped after 44 additional patients were randomised (1:1:1) to placebo, 2‐ or 4‐mg/kg golimumab. Due to insufficient power for the Phase 3 primary endpoint analysis (clinical response at week 6), efficacy analyses are considered exploratory and include all randomised patients. Results No dose–response was observed in Phase 2; however, higher serum golimumab exposure was associated with greater proportions of patients achieving more favourable clinical outcomes, clinical response and greater improvement in Mayo scores compared with placebo‐treated patients and those with lower serum concentrations. Among all randomised patients, numerically greater proportions were in clinical response at week 6 in the 2‐ and 4‐mg/kg golimumab groups compared with placebo [44.0% (33/75) and 41.6% (32/77) vs. 30.1% (22/73)]. Conclusions Efficacy with single‐dose golimumab IV induction was lower than expected and less than observed in the SC induction study. No new safety findings were observed. ClinicalTrials.gov Number, NCT00488774.